Wyniki wyszukiwania

1

Acute hypoxia modulates arachidonic acid metabolism in cat carotid bodies. Role of dopamine

100%

Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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1996

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tom 56

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nr 2

2

Ceramides and sphingosine-1-phosphate in molecular mechanisms of neuronal cell death

63%

Czubowicz K., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Ceramides, bioactive members of the sphingolipids can be generated by de novo synthesis, sphingomyelin hydrolysis and by acylation of sphingosine. Ceramides are known to regulate several cellular processes, including differentiation, growth suppression, cell senescence and apoptosis. The ceramide levels increased in several pathological conditions such as brain ischemia, hypoglycemia, inflammation and in neurodegenerative disorders. Sphingosine, a metabolite of ceramide is phosphorylated by sphingosine kinases (Sphk type 1and 2) to sphingosine-1-phosphate (S1P). Sphingosine kinases are critical regulators of the sphingolipid biostat. The aim of this study was to investigate the role of ceramide and S1P in molecular mechanisms of neuronal cells death. The human neuroblastoma cell line (SH-SY5Y) was exposed to cell-permeable C2-ceramide. Ceramide decreased the viability of SH-SY5Y cells in concentration dependent manner. The intracellular free radical generation after ceramide treatment was about 3-fold higher comparing to control. Concomitantly our study indicated that ceramide induced poly(ADP-ribose) polymerase-1 (PARP-1) activation and decreased the level of apoptosis inducing factor (AIF) in mitochondria. Ceramide diminished the expression and level of anti-apoptotic Bcl-2 protein. PARP-1 inhibitor enhanced the level of Bcl-2 protein and cells survival keeping the level of AIF in mitochondria unchanged. The recent studies indicated that ERK1/2 are involved directly in regulation of PARP-1 activity. The specific inhibitor of these kinases protected cells against death evoked by ceramide in our experimental conditions. Moreover, our study indicated, that sphingosine-1-phosphate (S1P) increased Bcl-2 gene expression and SH-SY5Y cells survival after ceramide treatment. Summarizing, our data present that PARP-1 inhibitor and sphingosine-1-phosphate (S1P) through modulation of anti-apoptotic proteins protect mitochondria and neuronal cells against death evoked by ceramide. Supported by statutory budget of MRC and NCN Grant 5870/PO1/2011/40

3

Effects of 3-aminobenzamide on ultrastructure of hippocampal CA1 layer after global ischemia in gerbils

63%

Strosznajder R. P., Walski M.

Journal of Physiology and Pharmacology. Supplement

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2004

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tom 55

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nr 3

127-133

Poly(ADP-ribose) polymerase (PARP EC 2.4.2.30) is a key enzyme in the DNA repair machinery, but its excessive stimulation during reperfusion after ischemia could play a critical role in cell death. Our previous study indicated that the PARP inhibitor 3-aminobenzamide (3-AB) significantly protected neuronal cells against death after a short ischemic insult. In this study we investigated the effect of 3-AB on the ischemia-evoked alterations in intracellular organelles. Gerbils were submitted to 3 min of transient forebrain ischemia followed by reinstitution of recirculation for 1-7 days. Electron microscopy showed only the signs of necrotic cell death after ischemia-reperfusion. The examination of specimens revealed a pronounced protective effect of 3-AB on the swelling of astrocytes and neurons 1 day after the ischemic insult. 3-AB also decreased the swelling of pericytes, but it had no effect on the accumulation of osmiophilic inclusions and fibril formation in astrocytes. 3-AB decreased the ischemia-induced swelling of mitochondria. The protective effects of 3-AB on cellular ultrastructure were also observed 7 days after reperfusion. These findings indicate that the inhibition of PARP may have a protective effect on cell swelling and on the state of intracellular organelles after a short-term ischemic episode.

4

Amyloid beta protein affects poly[ADP-ribose] polymerase activity in PC-12 cells in culture

63%

Strosznajder R. P., Banasik M.

Acta Neurobiologiae Experimentalis

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2000

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tom 60

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nr 2

5

ATP a potent regulator of inositol phospholipids-phospholipase C and lipid mediators in brain cortex

63%

Strosznajder J., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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1996

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tom 56

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nr 2

6

Role of lipoxygenases and poly(ADP-ribose) polymerase in amyloid beta cytotoxicity

51%

Cieslik M., Strosznajder J. B., Gajkowska B., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2011

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tom 71

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nr 1

The roles of 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the molecular processes evoked by amyloid β (Aβ) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human Aβ precursor protein. Different levels of Aβ secretion characterize these cells. The results demonstrated a relationship between the Aβ levels and LOX protein expression and activity. High Aβ concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-κB into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70-80 % of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding nontreated with SNP cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in Aβ toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies. Supported by MS&HE grant NN40113938 and MRC statutory theme No 7.

7

Effects of myriocin and FTY720 on gene expression of sphingolipid metabolism enzymes in animal model of Alzheimer’s disease

51%

Jesko H., Wencel P. L., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

INTRODUCTION: Sphingolipid imbalance has been observed in Alzheimer’s disease (AD) (accumulation of the pro-apoptotic ceramide, and loss of the protective sphingosine-1-phosphate – S1P) being correlated with the progress of neurodegeneration. Deregulated sphingolipid homeostasis may lead to neuronal death. Therefore enzymes regulating sphingolipid metabolism gain attention as highly promising targets in AD research/therapy. AIM(S): We examined the influence of myriocin and FTY720 on gene expression of enzymes metabolizing ceramide/sphingosine-1-phosphate in a mouse transgenic AD model. METHOD(S): mRNAs were measured with real-time PCR in the cerebral cortex of 6-months old FVB mice overexpressing human Aβ precursor protein (APP) treated with myriocin, a ceramide biosynthesis inhibitor, and FTY720 a sphingosine analog and sphingosine-1-phosphate receptor modulator. RESULTS: Myriocin has increased the expression of ceramidases ACER2 and -3, ceramide kinase (CERK), sphingosine kinase 2 (SPHK2) and S1P receptors (S1PR1 and -5) in APP mice. These results suggest a metabolic shift from ceramide towards the survival-promoting ceramide-1-phosphate and S1P. However, both Bcl-2 and Bax were increased, leaving the question open. The mock-transfected animals seemed to respond to treatment with a shift towards ceramide accumulation and dephosphorylation of S1P into sphingosine. FTY720 treatment of APP animals increased mRNA levels of ceramide synthases (CERS2 and 6), SPHK1 and 2, and proteins from Bcl-2 family. CONCLUSIONS: Our results suggest that myriocin and FTY720 treatment may lead to widespread modification of gene expression in the sphingolipid rheostat and signaling pathways, which requires further research to fully understand their mechanisms of action. FINANCIAL SUPPORT: Supported by the National Science Center grant no NCN/15/B/NZ3/01049.

8

The role of sphingosine kinases/sphingosine-1-phosphate in the regulation of alpha-synuclein and amyloid beta precursor protein secretion. Implications for neurodegenerative disorders

51%

Jesko H., Okada T., Nakamura S., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Sphingolipid deregulation may be an important factor of age-related neuronal stress vulnerability. Current data suggests potential links between sphingosine kinases (SphK1&2), their product sphingosine1-phosphate (S1P) and age-related protein conformation diseases. The aim of this study was to investigate a possible role of SphKs in alpha-synuclein (ASN) and amyloid beta (ABeta) precursor protein (APP) level and secretion. The studies were carried out using human SH-SY5Y neuroblastoma cell line stably transfected with the human gene for α-synuclein (ASNwt). Sphingosine kinase inhibitor (SKI) significantly increased ASN secretion in concentration-dependent manner. S1P also displayed similar influence. Neither compound exerted any significant effect on the ASN protein level. S1P may act via cell surface receptors or as an intracellular second messenger. The similar effect of S1P and SphK inhibitors on ASN secretion may suggest that the regulation of its release is critically dependent on the varied (intra)cellular targets of SphKs and downstream signaling pathways. We have found that stable human ASNwt expression in SH-SY5Y cells caused a three-fold, significant increase of the cellular APP level. In ASN-transfected cells S1P enhanced APP secretion and reduced its intracellular level. This could be linked to the recently reported effect of S1P on secretase beta activity. Inhibition of SphKs significantly decreased APP secretion. In summary our data indicates that endogenous ASN regulates APP level in SH-SY5Y cells and that sphingolipids play a crucial role in the secretion of ASN and APP. These processes may have significant impact on neuronal survival and health.

9

Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

51%

Adamczyk A., Czapski G. A., Jesko H., Strosznajder R. P.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 2

5-13

Amyloid beta peptide (Aß) and non-Aß component of Alzheimer’s disease amyloid (NAC) are involved in pathomechanism of Alzheimer's Disease (AD) and are deposited in the AD brain in the form of senile plaques. However, the mechanism of their neurotoxicity is not fully understood. In this study the sequence of events involved in NAC and Aß peptides evoked toxicity was investigated in brain slices, synaptosomes and in subcellular fractions. Radio-, immunochemical, spectrophotometrical methods and DNA electrophoresis were used in this study. Our data indicated that Aß 1-40 (25 µM) and NAC (10 µM) peptides induced liberation of free radicals and massive DNA damage that lead to activation of DNA bound enzyme poly(ADP-ribose) polymerase-1 (PARP-1). In consequence of these processes apoptosis-inducing factor (AIF) was released from mitochondria and was translocated to nucleus. The inhibitor of PARP, 3-aminobenzamide significantly decreased AIF release from mitochondria and its translocation. Both peptides under the investigated conditions had no effect on caspase-3 activity. Our data indicated that Aß and NAC peptides stimulate AIF-dependent apoptotic pathway that seems to be caspase independent process. The inhibition of PARP-1 may protect the brain against Aß and NAC toxicity.

10

Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus

51%

Strosznajder R. P., Jesko H., Adamczyk A.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

209-213

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation. The aim of this study was to investigate the role of PARP-1 in muscarinic cholinergic receptor signaling. Our data indicate that activation of muscarinic cholinergic receptors by carbachol (1mM) in the presence of GTPS evoked a significant enhancement of PARP activity in the adult rat hippocampus. Moreover, TMB-8 (10µM), an antagonist of inositol 1, 4, 5 trisphosphate (IP3) receptor prevented the activation of PARP-1, which indicates that IP3 /Ca2+ signaling is involved in this pathway. The diacylglycerol (DAG)-regulated protein kinase C (PKC) inhibitor (GF109203X) (1µM) only slightly enhanced PARP activity in hippocampal nuclear fractions, which suggests that DAG/ PKC is not involved in PARP activation.

11

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress

51%

Strosznajder R. P., Jesko H., Banasik M., Tanaka S.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

215-221

Our previous data indicate that ischemia and amyloid beta peptide (Abeta) cause an oxidative damage to macromolecules. In the present study we investigated the role of p53 protein in cell survival and death after administration of Abeta. The experiments were carried out on pheochromocytoma cells (PC-12) and cortical primary neurons in culture. The cortical neurons were exposed (48 h, 10 µM) to the action of a short Abeta25-35 neurotoxic fragment and the involvement of p53 was evaluated after addition of the p53 inhibitor pifithrin-alpha. Changes in cell morphology were evaluated by 4', 6-diamidino-2-phenylindole staining and the concentration-dependent effect of pifithrin-alpha on cells viability was determined. Additionally, we studied the effect of pifithrin-alpha on neuronal survival in vivo after a 5-min global brain ischemia followed by 7 days' reperfusion in gerbils. We found that Abeta enhanced apoptotic cell death in cortical primary neurons. Pifithrin-alpha, at a 10 µM final concentration, protected the neuronal cells from the apoptotic death. However, at concentrations of 0.1 and 1 mM, the p53 inhibitor decreased PC-12 cells' viability in a dose-dependent manner. In in vivo experiments we did not observe any neuroprotection by pifithrin-alpha in the CA1 hippocampal layer, which suggests that its effects strongly depend on the duration and type of an ischemic insult. Our data indicate that pifithrin-alpha affects neuronal cells in a dual manner. It has a protective effect at a low concentration, but becomes neurotoxic at higher concentrations.

12

Expression of poly(ADP-ribose) polymerases in hippocampus during systemic inflammatory response. The role of PARP-1 protein interactions in cognition

51%

Czapski G., Adamczyk A., Strosznajder R. P., Strosznajder J. B.

Acta Neurobiologiae Experimentalis

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2011

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tom 71

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nr 1

Poly(ADP-ribosyl)ation is covalent modification of proteins responsible for the alterations of their function. This process is catalyzed by poly(ADP-ribose)polymerases (PARP) family, consisted of 18 isoforms. Among target proteins, there are many DNA-related proteins and PARP-1 itself. In the brain, PARP-1 is responsible for more than 90% of poly(ADP-ribosyl)ation. PARP-1 plays a significant role in regulation of several transcription factors including NF-kB and p53. Our previous data indicated an important impact of PARP-1 in brain ischemia and in systemic inflammatory response (SIR). In this study we have analyzed the expression of PARP family genes in hippocampus of mice subjected to lipopolysaccharide (LPS)- evoked SIR. Moreover, the effect of SIR on PARP-1/PAR protein interaction and on memory function was evaluated. Mice C57BL6 were injected i.p. with LPS (1 mg/kg b.w.) alone or together with PARP inhibitors 3-aminobenzamide (30 mg/kg b.w.). The studies were carried out by using immunochemistry, microarray, real-time RT-PCR, and behavioral analysis. Our data indicated the small effect of SIR on PARP-1 gene expression level, however, expression of genes for PARP-3, -9, -12 and -14 was significantly increased 12 h after LPS administration. The level of PAR in hippocampus was elevated during SIR indicating activation of protein poly(ADP-ribosyl)ation. Moreover, further analysis of LPS-affected genes indicated that among 83 proteins known for their direct interaction with PARP-1, genes for 21 are present in SIR-related interactome, along with several genes for transcription factors and proteins involved in signal transduction. The enhancement of gene expression in hippocampus for several members of PARP family during SIR may be responsible for the alteration of PARPs function, higher level of PAR formation and for the modification of PARP/PAR protein interaction, transcription, cell signaling and memory. Our data indicated that SIR significantly decreases object recognition but has small effect on spatial memory. PARP-1 inhibitor protects against SIR induced molecular alteration in hippocampus and against SIR-evoked cognition impairment. Moreover, PARP-1 inhibitors significantly enhanced spatial memory in LPS treated mice. Our results indicate that inhibition of PARP-1 is a promising protective strategy during overactivation of inflammatory reaction. The role of other PARP family members in SIR is a target of our future investigation.

13

Fingolimod (FTY720 - modulator of sphingosine 1-phosphate receptors) alters genes expression of selected NADplus-dependent enzymes in an animal model of Alzheimer’s disease

51%

Wencel P., Jesko H., Strosznajder R. P.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

|

nr Suppl.1

INTRODUCTION: Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) belong to the family of NAD+ ‑dependent enzymes. Both are involved in the regulation of energy homeostasis, cellular stress response, and DNA repair. Recent data suggest that alterations of bioactive sphingolipids level as well as SIRTs and PARPs may be involved in Alzheimer’s disease (AD) pathology, finally leading to the progression of disease. AIM(S): In this study, the effect of FTY720 administration on mRNA levels of SIRTs and PARP‑1 in an animal model of AD was examined. METHOD(S): 3‑, 6‑, and 12‑month‑old (3M, 6M, 12M) FVB/APP+ transgenic mice with London APP (V717I) mutation were used in this study. Mice without the mutation (APP- ) were used as the control. Animals received i.p. FTY720 (1mg/kg b.w.) or NaCl (vehicle) for 2 weeks. Brain cortex was isolated and qPCR methods were applied. RESULTS: A significant downregulation of Sirt1 mRNA levels in the cortex of 3M APP+ mice vs. APP- was observed. We also observed a tendency for a reduction of 6M Sirt3 and Sirt4 mRNA levels in APP+ mice. Administration of FTY720 increased mRNA levels of Sirt1 in 3M APP+ mice as well as Parp1, Sirt1, 3, 5 in 6M APP+ mice compared to APP+ mice treated with vehicle. Moreover, FTY720 elevated Parp1, Sirt1, and Sirt3 mRNA levels in 12M APP+ mice. CONCLUSIONS: The results of our study revealed a potential link between bioactive sphingolipids and NAD+ ‑dependent enzymes. These results may also indicate an FTY720-modulatory role in SIRTs and PARPs gene expression and may offer a useful tool in the therapeutic strategy of neurodegenerative disorders. FTY720, through the activation of mitochondrial sirtuins (Sirt3,5), may improve anti-oxidative defense and protect cells against oxidative stress evoked by amyloid beta toxicity. Moreover, through activation of Sirt1 and Parp1 gene expression, FTY720 may enhance DNA repair processes. FINANCIAL SUPPORT: Supported by the National Science Centre grant no. NCN 2014/15/B/NZ3/01049 and Mossakowski MRC PAS statutory theme no.7.

14

Amyloid beta peptides evoke alteration of cholinergic phosphoinositide signals, lipid peroxidation and PARP activity in brain

51%

Zambrzycka A., Jesko H., Strosznajder R. P., Strosznajder J. B.

Acta Neurobiologiae Experimentalis

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1999

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tom 59

|

nr 3

15

Ceramide/sphingosine-1-phosphate in cellls survival and death: implication in Alzheimer’s disease

51%

Strosznajder R. P., Czubowicz K., Gassowska M., Cieslik M.

Acta Neurobiologiae Experimentalis

|

2013

|

tom 73

|

nr Suppl.1

Ceramide and sphingosine-1-phosphate (S1P) are very active sphingolipid messengers which play a crucial role in regulation of neuronal cells survival and death. Alternation of ceramide/S1P rheostat is related to several pathological disorders including Alzheimer’s disease. Ceramides are involved in cells proliferation, differentiation and apoptotic death, while S1P enhances cell proliferation and antagonizes apoptosis. S1P regulates cellular processes by binding to five specific G protein coupled-receptors (S1PR1-5). The aim of the study was to investigate the molecular processes of neuronal death evoked by ceramide and the role of S1P in neuroprotection. Our study indicated that ceramide enhanced significantly the level of free radicals and decreased neuronal cells (SHSY5Y) viability through inhibition of PI3-K/Akt pathway. Ceramide also decreased anti-apoptotic (Bcl-2) and increased pro-apoptotic (Bax, Hrk) gene expression. Exogenously added S1P increased the viability of cells through S1PR (1-3) receptors-dependent mechanism. S1P also increased Bcl-2 gene expression and decreased the gene expression of Hrk protein. Summarizing, our study indicated that the action of ceramide and S1P on mitochondria may control neuronal fate and may play a crucial role in neurodegeneration and neuroprotection.

16

Age-related alteration of poly[ADP-ribose] polymerase activity in different parts of the brain

51%

Strosznajder J. B., Jesko H., Strosznajder R. P.

Acta Biochimica Polonica

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2000

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tom 47

|

nr 2

Poly(ADP-ribose) polymerase (PARP) is a conserved enzyme involved in the regulation of DNA repair and genome stability. The role of PARP during aging is not well known. In this study PARP activity was investigated in nuclear fractions from hippocampus, cerebellum, and cerebral cortex of adult (4 months), old adult (14 months) and aged (24-27 months) rats. Concomitantly, the free radical evoked lipid peroxidation was estimated as thiobarbituric acid reactive substances (TBARS). The specific activity of PARP in adult brain was about 25, 21 and 16 pmol/mg protein per min in hippocampus, cerebellum and cerebral cortex, respectively. The enzyme activity was higher in all investigated parts of the brain of old adults. In aged animals PARP activity was lower in hippocampus by about 50%, and was unchanged in cerebral cortex and in cerebellum comparing to adult rats. The concentration of TBARS was the same in all parts of the brain and remained unchanged during aging. There is no direct correlation between PARP activity and free radical evoked lipid peroxidation during brain aging. The lowered enzyme activity in aged hippocampus may decrease DNA repair capacity which subsequently may be responsible for the higher vulnerability of hippocampal neurons to different toxic insults.

17

Effect of carvedilol on neuronal survival and poly[ADP-ribose] polymerase activity in hippocampus after transient forebrain ischemia

51%

Strosznajder R. P., Jesko H., Dziewulska J.

Acta Neurobiologiae Experimentalis

|

2005

|

tom 65

|

nr 2

18

Effect of aging and oxidative-genotoxic stress on poly[ADP-ribose] polymerase-1 activity in rat brain

51%

Strosznajder R. P., Jesko H., Adamczyk A.

Acta Biochimica Polonica

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2005

|

tom 52

|

nr 4

Poly(ADP-ribose) polymerase-1 (PARP-1, EC 2.4.2.30), a DNA-bound enzyme, plays a key role in genome stability, but after overactivation can also be responsible for cell death. The aim of the present study was to investigate PARP-1 activity in the hippocampus, brain cortex, striatum and cerebellum in adult (4 months) and aged (24 months) specific pathogen free Wistar rats and to correlate it with PARP-1 protein level and p53 expression. Moreover, the response of PARP-1 in adult and aged hippocampus to oxidative/genotoxic stress was evaluated. Our data indicated a statistically significant enhancement of PARP-1 activity in aged hippocampus and cerebral cortex comparing to adults without statistically significant changes in PARP-1 protein level. The expression of p53 mRNA was elevated in all aged brain parts with the exception of the cerebral cortex. Our data suggest that enhancement of PARP-1 activity and p53 expression in aged brain may indicate higher DNA damage. Our data also indicate that during excessive oxidative/genotoxic stress there is no response of PARP-1 activity in aged hippocampus in contrast to a significant enhancement of PARP-1 activity in adults which may have important consequences for the physiology and pathology of the brain.

19

Effect of amyloid beta peptide on poly[ADP-ribose] polymerase activity in adult and aged rat hippocampus

51%

Strosznajder J. B., Jesko H., Strosznajder R. P.

Acta Biochimica Polonica

|

2000

|

tom 47

|

nr 3

It is suggested that the fibrillar amyloid beta peptide (Abeta) in brain plays a direct role in neurodegeneration in Alzheimer's disease, probably through activation of reactive oxygen species formation. Free radicals and numerous neurotoxins elicit DNA damage that subsequently activates poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30). In this study the effect of neurotoxic fragment (25-35) of full length Abeta peptide on PARP activity in adult and aged rat hippocampus was investigated. In adult (4 month old) rat hippocampus the Abeta 25-35 peptide significantly enhanced PARP activity by about 80% but had no effect on PARP activity in cerebral cortex and in hippocampus from aged (24-27 month old) rats. The effect of Abeta peptide was reduced by half by the nitric oxide synthase inhibitor N-nitro-L-arginine. Stimulation of glutamate receptor(s) itself enhanced PARP activity by about 80% in adult hippocampus. However, Abeta 25-35 did not exert any additional stimulatory effect. These results indicate that Abeta, through NO and probably other free radicals, induces activation of DNA bound PARP activity exclusively in adult but not in aged hippocampus.

20

Poly(ADP-ribose) polymerase activity in the cat carotid body in hypoxia and hyperoxia

51%

Strosznajder R. P., Jesko H., Pokorski M.

Journal of Physiology and Pharmacology

|

2002

|

tom 53

|

nr 3

Reactive oxygen species (ROS) induce DNA damage with the ensuing activation of the chromosomal repair enzyme poly(ADP-ribose) polymerase (PARP). ROS also interact with the function of carotid body chemoreceptor cells. The possibility arises that PARP is part of the carotid chemosensing process. This study seeks to determine the presence of PARP and its changes in response to contrasting chemical stimuli, hypoxia and hyperoxia, both capable of generating ROS, in cat carotid bodies. The organs were dissected from anesthetized cats exposed in vivo to acute normoxic (PaO290 mmHg), hypoxic (PaO225 mmHg), and hyperoxic (PaO2> 400 mmHg) conditions. Carotid body homogenate was the source of PARP and [adenine 14C] NAD was the substrate in the assay. Specimens of the superior cervical ganglion and brainstem were used as reference tissues. We found that PARP activity amounted to 27 pmol/mg protein/min in the normoxic carotid body. The activity level more than doubled in both hypoxic and hyperoxic carotid bodies. Changes of PARP in the reference tissues were qualitatively similar. We conclude that PARP is present in the carotid body but the augmentation of the enzyme activity in both hypoxia and hyperoxia reflects DNA damage, induced likely by ROS and being universal for neural tissues, rather than a specific involvement of PARP in the chemosensing process.

Ograniczanie wyników

Acute hypoxia modulates arachidonic acid metabolism in cat carotid bodies. Role of dopamine

Ceramides and sphingosine-1-phosphate in molecular mechanisms of neuronal cell death

Effects of 3-aminobenzamide on ultrastructure of hippocampal CA1 layer after global ischemia in gerbils

Amyloid beta protein affects poly[ADP-ribose] polymerase activity in PC-12 cells in culture

ATP a potent regulator of inositol phospholipids-phospholipase C and lipid mediators in brain cortex

Role of lipoxygenases and poly(ADP-ribose) polymerase in amyloid beta cytotoxicity

Effects of myriocin and FTY720 on gene expression of sphingolipid metabolism enzymes in animal model of Alzheimer’s disease

The role of sphingosine kinases/sphingosine-1-phosphate in the regulation of alpha-synuclein and amyloid beta precursor protein secretion. Implications for neurodegenerative disorders

Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

Poly(ADP-ribose) polymerase-1 is a novel nuclear target for cholinergic receptor signaling in the hippocampus

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress

Expression of poly(ADP-ribose) polymerases in hippocampus during systemic inflammatory response. The role of PARP-1 protein interactions in cognition

Fingolimod (FTY720 - modulator of sphingosine 1-phosphate receptors) alters genes expression of selected NADplus-dependent enzymes in an animal model of Alzheimer’s disease

Amyloid beta peptides evoke alteration of cholinergic phosphoinositide signals, lipid peroxidation and PARP activity in brain

Ceramide/sphingosine-1-phosphate in cellls survival and death: implication in Alzheimer’s disease

Age-related alteration of poly[ADP-ribose] polymerase activity in different parts of the brain

Effect of carvedilol on neuronal survival and poly[ADP-ribose] polymerase activity in hippocampus after transient forebrain ischemia

Effect of aging and oxidative-genotoxic stress on poly[ADP-ribose] polymerase-1 activity in rat brain

Effect of amyloid beta peptide on poly[ADP-ribose] polymerase activity in adult and aged rat hippocampus

Poly(ADP-ribose) polymerase activity in the cat carotid body in hypoxia and hyperoxia