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UCP4 is a key regulator of mitochondrial antioxidant defense in rat PC12 cells
Author(s) -
Kamga Christelle K.,
Zhang Shelley X.L.,
Fentress Emily S,
Wang Yang
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.716.10
Subject(s) - reactive oxygen species , microbiology and biotechnology , apoptosis , mitochondrion , mitochondrial ros , gene silencing , downregulation and upregulation , chemistry , biology , biochemistry , gene
Reactive oxygen species (ROS)‐induced cellular injury contributes to the pathogenesis of neuronal disorders. Uncoupling proteins (UCPs) facilitate electron flows on the mitochondrial membrane and are expected to decrease ROS production. We previously showed that silencing of UCP4, a central nervous system‐specific UCP, led to apoptosis in PC12 cells. The purpose of the current study was to define the effects of UCP4 on ROS homeostasis and on mitochondrial antioxidants by contrasting the effects of UCP4‐silencing and overexpression. ROS levels were significantly increased in UCP4‐silencing (S2) cells (251.4±1.4% of. controls) but decreased in UCP4‐overexpressing (hUCP4) cells (73.3±1.4% of. controls). MnSOD was upregulated in S2 cells but downregulated in hUCP4 cells. Peroxiredoxin III was significantly downregulated in S2 cells but maintained in hUCP4 cells. Furthermore, mitochondrial levels of GSH were significantly decreased in S2 cells (51.9±8.4% of controls), which was associated with reduced expression of dicarboxylate carrier, a mitochondrial GSH transporter, but increased in hUCP4 cells (155.6±23.1% of. controls). These findings suggest that UCP4 may regulate ROS levels by modifying mitochondrial antioxidants, especially those that are important in reducing H 2 O 2 and preventing the formation of hydroxyl radicals. UCP4 may thus be a therapeutic target for ROS‐induced neuronal disorders.