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The radical scavenger CR‐6 protects SH‐SY5Y neuroblastoma cells from oxidative stress‐induced apoptosis: effect on survival pathways
Author(s) -
Sanvicens Nuria,
GómezVicente Violeta,
Messeguer Angel,
Cotter Thomas G.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03914.x
Subject(s) - sh sy5y , apoptosis , oxidative stress , calpain , caspase , microbiology and biotechnology , reactive oxygen species , proteases , programmed cell death , neurodegeneration , free radical scavenger , chemistry , biology , oxidative phosphorylation , neuroblastoma , biochemistry , cell culture , cancer research , medicine , enzyme , genetics , disease
Reactive oxygen species (ROS) and oxidative stress have long been linked to cell death of neurons in many neurodegenerative conditions. However, the exact molecular mechanisms triggered by oxidative stress in neurodegeneration are at present unclear. In the current work we have used the human neuroblastoma SH‐SY5Y cell line as a model for studying the molecular events occurring after inducing apoptosis with H 2 O 2 . We show that treatment of SH‐SY5Y cells with H 2 O 2 up‐regulates survival pathways during early stages of apoptosis. Subsequently, the decline of anti‐apoptotic protein levels leads to the activation of the calcium‐dependent proteases calpains and the cysteine proteases caspases. Additionally, we demonstrate that CR‐6 (3,4‐dihydro‐6‐hydroxy‐7‐methoxy‐2,2‐dimethyl‐1(2H)‐benzopyran) acts as a scavenger of ROS and prevents apoptosis by enhancing and prolonging up‐regulation of survival pathways. Furthermore, we show that pre‐treatment of SH‐SY5Y cells with a cocktail containing CR‐6, the pan‐caspase inhibitor zVAD‐fmk (zVal‐Ala‐Asp‐fluoro‐methylketone) and the calpain inhibitor SJA6017 confers almost total protection against apoptosis. In summary, the present work characterizes the molecular mechanisms involved in oxidative stress‐induced apoptosis in SH‐SY5Y cells. Our findings highlight the relevance of CR‐6, alone or in combination with other drugs, as potential therapeutic strategy for the treatment of neurodegenerative diseases.