A novel role for connexin hemichannel in oxidative stress and smoking-induced cell injury.
Oxidative stress is linked to many pathological conditions, including ischemia, atherosclerosis and neurodegenerative disorders. The molecular mechanisms of oxidative stress induced pathophysiology and cell death are currently poorly understood. Our present work demonstrates that oxidative stress induced by reactive oxygen species and cigarette smoke extract depolarize the cell membrane and open connexin hemichannels. Under oxidative stress, connexin expression and connexin silencing resulted in increased and reduced cell deaths, respectively. Morphological and live/dead assays indicate that cell death is likely through apoptosis. Our studies provide new insights into the mechanistic role of hemichannels in oxidative stress induced cell injury.
Ramachandran
Srinivasan
S
Center for Nanomedicine, The University of Chicago, Illinois, United States of America.
Xie
Lai-Hua
LH
John
Scott A
SA
Subramaniam
Shankar
S
Lal
Ratnesh
R
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D020868:Gene Silencing; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007546:Isoquinolines / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
D018031:Connexin 43; D003470:Culture Media; D005456:Fluorescent Dyes; D007546:Isoquinolines; D016877:Oxidants; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C017475:lucifer yellow; D006861:Hydrogen Peroxide; D002118:Calcium