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AMP‐activated protein kinase activation stimulates heme oxygenase‐1 gene expression in human vascular endothelium
Author(s) -
Liu Xiaoming,
Peyton Kelly J.,
Wang Hong,
Korthuis Ronald J.,
Durante William
Publication year - 2009
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.23.1_supplement.637.3
Subject(s) - ampk , protein kinase a , amp activated protein kinase , heme oxygenase , chemistry , umbilical vein , kinase , heme , microbiology and biotechnology , medicine , endocrinology , biochemistry , biology , enzyme , in vitro
AMP‐activated protein kinase (AMPK) is an energy sensing enzyme that is activated in response to changes in cellular metabolism. Recent studies indicate that AMPK inhibits endothelial cell (EC) activation and apoptosis, but the underlying mechanisms remain unclear. Since heme oxygenase‐1 (HO‐1) is a critical vasoprotective protein, the present study investigated whether AMPK activation induces HO‐1 expression in cultured human umbilical vein ECs. Treatment of ECs with the AMPK activators 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR; 0.1‐1mM) or metformin (0.5‐2mM) stimulated a concentration‐ and time‐dependent increase in HO‐1 protein. A significant rise in HO‐1 protein was first detected after 4 hours, peaked at 8 hours, and persisted for 24 hours after AMPK activation. AICAR‐mediated increases in HO‐1 protein were preceded by significant elevations in HO‐1 mRNA beginning 1 hour after AICAR treatment. The induction of HO‐1 by AICAR was inhibited by the AMPK inhibitor compound C, the transcriptional inhibitor actinomycin D, and the antioxidant N‐acetyl‐L‐cysteine. In conclusion, this study demonstrates that AMPK stimulates HO‐1 gene expression in human ECs via a transcriptional and redox‐sensitive pathway. The ability of AMPK to induce HO‐1 may provide an important mechanism by which this kinase preserves EC function during periods of metabolic stress. Supported by NIH and AHA.