콘텐츠로 건너뛰기
Merck
  • Carbon monoxide induces heme oxygenase-1 to modulate STAT3 activation in endothelial cells via S-glutathionylation.

Carbon monoxide induces heme oxygenase-1 to modulate STAT3 activation in endothelial cells via S-glutathionylation.

PloS one (2014-07-30)
Yan-Chang Yang, Yu-Ting Huang, Chia-Wen Hsieh, Po-Min Yang, Being-Sun Wung
초록

IL-6/STAT3 pathway is involved in a variety of biological responses, including cell proliferation, differentiation, apoptosis, and inflammation. In our present study, we found that CO releasing molecules (CORMs) suppress IL-6-induced STAT3 phosphorylation, nuclear translocation and transactivity in endothelial cells (ECs). CO is a byproduct of heme degradation mediated by heme oxygenase (HO-1). However, CORMs can induce HO-1 expression and then inhibit STAT3 phosphorylation. CO has been found to increase a low level ROS and which may induce protein glutathionylation. We hypothesized that CORMs increases protein glutathionylation and inhibits STAT3 activation. We found that CORMs increase the intracellular GSSG level and induce the glutathionylation of multiple proteins including STAT3. GSSG can inhibit STAT3 phosphorylation and increase STAT3 glutathionylation whereas the antioxidant enzyme catalase can suppress the glutathionylation. Furthermore, catalase blocks the inhibition of STAT3 phosphorylation by CORMs treatment. The inhibition of glutathione synthesis by BSO was also found to attenuate STAT3 glutathionylation and its inhibition of STAT3 phosphorylation. We further found that HO-1 increases STAT3 glutathionylation and that HO-1 siRNA attenuates CORM-induced STAT3 glutathionylation. Hence, the inhibition of STAT3 activation is likely to occur via a CO-mediated increase in the GSSG level, which augments protein glutathionylation, and CO-induced HO-1 expression, which may enhance and maintain its effects in IL-6-treated ECs.

MATERIALS
제품 번호
브랜드
제품 설명

Serine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
MISSION® esiRNA, targeting human HMOX1
Diacetylfluorescein, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Fluorescein diacetate, used as cell viability stain
Sigma-Aldrich
DL-Serine, ≥98% (TLC)
Sigma-Aldrich
DL-Serine, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98% (HPLC)
Tyrosine, European Pharmacopoeia (EP) Reference Standard