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2009 | 69 | 3 |
Tytuł artykułu

An involvement MAPK/ERK1/2 pathway in mechanism of lactacystin-induced cell damage in primary cortical neurons

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Proteasome dysfunction is involved in pathomechanism of several neurodegenerative diseases where an accumulation of aberrant proteins occurs (e.g. Parkinson’s disease, Alzheimer’s disease). Lactacystin (LC) has been used for induction of proteasome inhibition-dependent neuronal cell death for several years but mechanism of its toxic action on neurons is still poorly understood. In the present study we showed time- and concentration-dependent toxic action of lactacystin (0.25–50 μM) in mouse cortical neurons. Although, lactacystin induced caspase-3 activation, its toxic action was not attenuated by caspase-3 inhibitor AcDEVD-CHO. We demonstrated that inhibitors of MAPK/ERK1/2 cellular signaling (U0126 and PD98052) were protective against LC-evoked cell death as confi rmed by LDH and MTT reduction assays. Moreover, these data were verifi ed by Western Blot analysis, where we observed the increase in ERK1/2 activity after LC treatment and this effect was inhibited by U0126. The obtained data point to engagement of activation of MAPK/ERK1/2 in toxic action of lactacystin and give a rationale for using agents which inhibit this intracellular pathway in treatment of neurodegenerative diseases connected with proteasome dysfunction. Supported by Polish MNSW Scientifi c Network Fund no 26/E-40/BWSN-0023/2008.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.344
Twórcy
autor
  • Department of Experimental Neuroendocrinology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
autor
  • Department of Neuropsychopharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
autor
  • Department of Neuropsychopharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
autor
  • Department of Experimental Neuroendocrinology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
  • Department of Neuropsychopharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-e89b550e-3c94-47c5-8d19-52002c963624
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