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REDOX PROPERTIES OF ATP‐SENSITIVE K+ CHANNELS IN BRAIN MITOCHONDRIA
Author(s) -
Fornazari Maynara,
Paula Juliana,
Castilho Roger Frigerio,
Kowaltowski Alicia Juliana
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1017.2
Subject(s) - mitochondrion , diazoxide , microbiology and biotechnology , reactive oxygen species , chemistry , excitotoxicity , adenosine triphosphate , biochemistry , biophysics , programmed cell death , biology , apoptosis , endocrinology , insulin
Brain mitochondrial ATP‐sensitive K + channel (mitoK ATP ) opening by diazoxide protects against ischemic damage and excitotoxic cell death. We studied here the redox properties of brain mitoK ATP . MitoK ATP activation during excitotoxicity in cultured cerebellar granule neurons prevented the accumulation of reactive oxygen species (ROS) and cell death. Furthermore, mitoK ATP activation in isolated brain mitochondria significantly prevented H 2 O 2 release by these organelles, but did not change Ca 2+ accumulation capacity. Interestingly, the activity of mitoK ATP was highly dependent on redox state. Thiol reductant mercaptopropionylglycine prevented mitoK ATP activity, while exogenous ROS activated the channel. In addition, the use of mitochondrial substrates that lead to higher levels of endogenous mitochondrial ROS release closely correlated with enhanced K + transport activity through mitoK ATP . Altogether, our results indicate that brain mitoK ATP is a redox‐sensitive channel that controls mitochondrial ROS release. Supported by FAPESP, CNPq, Redoxoma, Guggenheim Foundation and the NIH.