| First Author | Choi YK | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 479 |
| Issue | 2 | Pages | 297-304 |
| PubMed ID | 27639646 | Mgi Jnum | J:239132 |
| Mgi Id | MGI:5824976 | Doi | 10.1016/j.bbrc.2016.09.063 |
| Citation | Choi YK, et al. (2016) Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca2+ channel-mediated PGC-1alpha/ERRalpha activation. Biochem Biophys Res Commun 479(2):297-304 |
| abstractText | Carbon monoxide (CO), derived by the enzymatic reaction of heme oxygenase (HO), is a cellular regulator of energy metabolism and cytoprotection; however, its underlying mechanism has not been clearly elucidated. Astrocytes pre-exposed to the CO-releasing compound CORM-2 increased mitochondrial biogenesis, mitochondrial electron transport components (cytochrome c, Cyt c; cytochrome c oxidase subunit 2, COX2), and ATP synthesis. The increased mitochondrial function was correlated with activation of AMP-activated protein kinase alpha and upregulation of HO-1, peroxisome proliferators-activated receptor gamma-coactivator-1alpha (PGC-1alpha), and estrogen-related receptor alpha (ERRalpha). These events elicited by CORM-2 were suppressed by Ca2+ chelators, a HO inhibitor, and an L-type Ca2+ channel blocker, but not other Ca2+ channel inhibitors. Among the HO byproducts, combined CORM-2 and bilirubin treatment effectively increased PGC-1alpha, Cyt c and COX2 expression, mitochondrial biogenesis, and ATP synthesis, and these increases were blocked by Ca2+ chelators. Moreover, cerebral ischemia significantly increased HO-1, PGC-1alpha, and ERRalpha levels, subsequently increasing Cyt c and COX2 expression, in wild-type mice, compared with HO-1+/- mice. These results suggest that HO-1-derived CO enhances mitochondrial biogenesis in astrocytes by activating L-type Ca2+ channel-mediated PGC-1alpha/ERRalpha axis, leading to maintenance of astrocyte function and neuroprotection/recovery against damage of brain function. |
