Premium
NF‐κB‐mediated up‐regulation of Bcl‐X S and Bax contributes to cytochrome c release in cyanide‐induced apoptosis
Author(s) -
Shou Yan,
Li Nianyu,
Li Li,
Borowitz Joseph L.,
Isom Gary E.
Publication year - 2002
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 - 10.1046/j.1471-4159.2002.00880.x
Subject(s) - cytochrome c , apoptosis , cyanide , biology , bcl 2 associated x protein , cytochrome , mitochondrion , microbiology and biotechnology , reactive oxygen species , western blot , chemistry , biochemistry , programmed cell death , caspase 3 , enzyme , gene , inorganic chemistry
Cyanide induces apoptosis through cytochrome c activated caspase cascade in primary cultured cortical neurons. The underlying mechanism for cytochrome c release from mitochondria after cyanide treatment is still unclear. In this study, the roles of endogenous Bcl‐2 proteins in cyanide‐induced apoptosis were investigated. After cyanide (100–500 µ m ) treatment for 24 h, two pro‐apoptotic Bcl‐2 proteins, Bcl‐X S and Bax were up‐regulated as shown by western blot and RT‐PCR analysis. The expression levels of two antiapoptotic Bcl‐2 proteins, Bcl‐2 and Bcl‐X L , remained unchanged after cyanide treatment, whereas the mRNA levels of Bcl‐X S and Bax began to increase within 2 h and their protein levels increased 6 h after treatment. NF‐κB, a redox‐sensitive transcription factor activated after cyanide treatment, is responsible for the up‐regulation of Bcl‐X S and Bax. SN50, which is a synthetic peptide that blocks translocation of NF‐κB from cytosol to nucleus, inhibited the up‐regulation of Bcl‐X S and Bax. Similar results were obtained using a specific κB decoy DNA. NMDA receptor activation and reactive oxygen species (ROS) generation are upstream events of NF‐κB activation, as blockade of these two events by MK801, l ‐NAME or PBN inhibited cyanide‐induced up‐regulation of Bcl‐X S and Bax. Up‐regulation of pro‐apoptotic Bcl‐X S and Bax contributed to cyanide‐induced cytochrome c release, because SN50 and a specific Bax antisense oligodeoxynucleotide significantly reduced release of cytochrome c from mitochondria as shown by western blot analysis. It was concluded that NF‐κB‐mediated up‐regulation of Bcl‐X S and Bax is involved in regulating cytochrome c release in cyanide‐induced apoptosis.