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Angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers affect kynurenic acid production in rat brain cortex in vitro

100%

Zakrocka I., Targowska-Duda K. M., Wnorowski A., Kocki T., Jozwiak K., Turski W. A.

Acta Neurobiologiae Experimentalis

2017

tom 77

nr Suppl.1

INTRODUCTION: Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II type 1 receptor blockers (ARBs) possess antihypertensive and neuroprotective properties. Kynurenic acid (KYNA), a broad spectrum glutamate antagonist is produced from L-kynurenine by kynurenine aminotransferases (KAT), mainly by KAT I and KAT II isoforms. AIM(S): The goal of our study was to analyze the effect of ACE-Is and ARBs on KYNA synthesis and KATs activity in rat brain cortex in vitro. METHOD(S): The influence of ACE‑Is (lisinopril, perindopril and ramipril) and ARBs (irbesartan, losartan, telmisartan) on KYNA production and KATs activity was examined. Slices and homogenates of rat brain cortex were incubated for 2 hours in the presence of L-kynurenine and examined ACE-I or ARB. KYNA was separated by HPLC and quantified fluorometrically. Moreover, the molecular docking of ARBs to KAT II and the analysis of KAT II coding genes expression in human and rat cerebral cortex were performed. RESULTS: ACE‑Is differently influenced KYNA synthesis and KATs activity in rat brain cortex in vitro. All examined ARBs decreased KYNA production and both KAT I and KAT II activity in rat brain cortex in vitro. Molecular docking showed that analyzed ARBs can bind to an active site of KAT II. CONCLUSIONS: Our study indicates that ACE-Is and ARBs may change KYNA production in rat brain cortex in vitro. ARBs inhibitory effect on KATs activity and KYNA synthesis suggest that ARBs may have beneficial effect in schizophrenia or dementia. FINANCIAL SUPPORT: This study was supported by National Science Centre (NCN) grant PRELUDIUM 4, No UMO-2012/07/N/NZ4/02088.

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Metabolic activity of tree saps of different origin towards cultured human cells in the light of grade correspondence analysis and multiple regression modeling

100%

Wnorowski A., Bilek M., Stawarczyk K., Gostkowski M., Olszewski M., Wojciak-Kosior M., Sowa I.

Acta Societatis Botanicorum Poloniae

2017

tom 86

nr 2

Tree saps are nourishing biological media commonly used for beverage and syrup production. Although the nutritional aspect of tree saps is widely acknowledged, the exact relationship between the sap composition, origin, and effect on the metabolic rate of human cells is still elusive. Thus, we collected saps from seven different tree species and conducted composition-activity analysis. Saps from trees of Betulaceae, but not from Salicaceae, Sapindaceae, nor Juglandaceae families, were increasing the metabolic rate of HepG2 cells, as measured using tetrazolium-based assay. Content of glucose, fructose, sucrose, chlorides, nitrates, sulphates, fumarates, malates, and succinates in sap samples varied across different tree species. Grade correspondence analysis clustered trees based on the saps’ chemical footprint indicating its usability in chemotaxonomy. Multiple regression modeling showed that glucose and fumarate present in saps from silver birch (Betula pendula Roth.), black alder (Alnus glutinosa Gaertn.), and European hornbeam (Carpinus betulus L.) are positively affecting the metabolic activity of HepG2 cells.

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Acta Societatis Botanicorum Poloniae

2 Wnorowski A.

1 Bilek M.

1 Gostkowski M.

1 Jozwiak K.

1 Kocki T.

1 Olszewski M.

1 Sowa I.

1 Stawarczyk K.

1 Targowska-Duda K. M.

1 Turski W. A.

1 Wojciak-Kosior M.

1 Zakrocka I.

2 2017

Wyniki wyszukiwania

Angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers affect kynurenic acid production in rat brain cortex in vitro

Metabolic activity of tree saps of different origin towards cultured human cells in the light of grade correspondence analysis and multiple regression modeling