Premium
Inactivation of glutathione peroxidase by nitric oxide leads to the accumulation of H 2 O 2 and the induction of HB‐EGF via c‐Jun NH 2 ‐terminal kinase in rat aortic smooth muscle cells
Author(s) -
Koh Young Ho,
Suzuki Keiichiro,
Che Wenyi,
Park Yong Seek,
Miyamoto Yasuhide,
Higashiyama Shigeki,
Taniguchi Naoyuki
Publication year - 2001
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/fj.00-0572fje
Subject(s) - nitric oxide , epidermal growth factor , chemistry , heparin binding egf like growth factor , peroxidase , microbiology and biotechnology , growth factor , biochemistry , biology , enzyme , receptor , organic chemistry
We describe the effect of nitric oxide (NO) on the expression of the heparin‐binding EGF‐like growth factor (HB‐EGF), a potent chemoattractant and mitogen for smooth muscle cells, and its anti‐apoptotic effect against NO cytotoxicity. Previous studies have shown that glutathione peroxidase (GPx), a major peroxide scavenging enzyme is selectively inactivated by an NO donor, S ‐nitroso‐ N ‐acetyl‐DL‐penicillamine (SNAP), in vitro and in vivo and results in the accumulation of peroxide (6, 7). The SNAP or peroxynitrite induces HB‐EGF through the inactivation of GPx and the accumulation of peroxide. This induction is accompanied by JNK and c‐Jun/AP‐1 activation. The blocking of the HB‐EGF induction by curcumin, c‐jun antisense oligonucleotide, and a dominant‐negative mutant of JNK1 provides support for these results. A longer pretreatment of rat aortic smooth muscle cells (RASMCs) by SNAP induces HB‐EGF and reduces the TNFα+actinomycin D‐induced apoptosis. This protection is blocked by antisense HB‐EGF s‐oligonucleotide. These findings indicate that the induction of HB‐EGF by NO would be an adaptive response as an autocrine protective factor against apoptosis by NO in RASMCs.