Premium
Protection against MPP + neurotoxicity in cerebellar granule cells by antioxidants
Author(s) -
GonzálezPolo Rosa A.,
Soler Germán,
Rodrıguezmartın Andrea,
Morán Jose M.,
Fuentes José M.
Publication year - 2004
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2004.03.005
Subject(s) - chemistry , reactive oxygen species , neurotoxicity , excitotoxicity , biochemistry , superoxide dismutase , mitochondrial ros , programmed cell death , peroxynitrite , nitric oxide , antioxidant , glutathione , pharmacology , superoxide , apoptosis , biology , enzyme , toxicity , organic chemistry
The neuropathology associated with Parkinson's disease (PD) is thought to involve excessive production of free radicals, dopamine autoxidation, defects in glutathione peroxidase expression, attenuated levels of reduced glutathione, altered calcium homeostasis, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and 1‐methyl‐4‐phenylpyridinium ion (MPP + ), both are thought to involve free radical production, compromised mitochondrial activity and excessive lipid peroxidation. We show here that the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) increased significantly after treatment of cultured cerebellar granule cells (CGCs) with 50 μM MPP + . Co‐treatment with antioxidants such as ascorbate (ASC), catalase, α‐tocopherol (α‐TOH), coenzyme Q 10 (CoQ 10 ) or superoxide dismutase (SOD) rescued the cells from MPP + ‐induced death. MPP + ‐induced cell death was also abolished by co‐treatment with nitric oxide synthase (NOS) inhibitors such as 7‐nitroindazole (7‐NI), 2‐ethyl‐2‐thiopseudourea hydrobromide (EPTU) or S ‐methylisothiourea sulphate (MPTU). We also tested the protective effects of an iron chelator (deferoxamine mesylate, DFx) and a peroxynitrite scavenger (FeTTPS) and the results lend further support to the view that the free radical cytotoxicity plays an essential role in MPP + ‐induced death in primary cultures of CGC.