Induction of small G protein RhoB by non-genotoxic stress inhibits apoptosis and activates NF-κB.
It has been reported by us and other groups that the expression of small GTP binding protein RhoB can be induced by genotoxic stressors and glucocorticoid (GC), a stress hormone that plays a key role in stress response. Until now stress-induced genes that confer cytoprotection under stressed conditions are largely unknown. In this study, we investigated the effects and mechanism of non-genotoxic stressors, including scalding in vivo and heat stress in vitro on the expression of RhoB. We found for the first time that both scalding, which could induce typical neuroendocrine responses of acute stress and cellular heat stress significantly increased the expression of RhoB at mRNA and protein levels. Moreover, in vitro experiments in human lung epithelial cells (A549) showed that induction of RhoB by heat stress was in a glucocorticoid receptor (GR)-independent manner and through multiple pathways including stabilization of RhoB mRNA and activation of p38 MAPK. Further experiments demonstrated that up-regulation of RhoB significantly inhibited heat stress-induced apoptosis and elevated transcriptional activity of NF-κB, but did not affect the expression of Hsp70 in A549 cells. In conclusion, we showed for the first time that RhoB was up-regulated by scalding in vivo and heat stress in vitro and played an important cytoprotective role during heat stress-induced apoptotic cell death.
Li
Yi-Dong
YD
Department of Pathophysiology, Second Military Medical University, and Department of Burn Surgery, Changhai Hospital, Shanghai, People's Republic of China.
Liu
Ya-Ping
YP
Cao
Dong-Mei
DM
Yan
Ya-Min
YM
Hou
You-Na
YN
Zhao
Jie-Ying
JY
Yang
Rui
R
Xia
Zhao-Fan
ZF
Lu
Jian
J
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D019610:Cytoprotection; D004249:DNA Damage; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D006801:Humans; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D048051:p38 Mitogen-Activated Protein Kinases; D020743:rhoB GTP-Binding Protein