RT Journal Article
SR Electronic
T1 A Central Role of Connexin 43 in Hypoxic Preconditioning
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 681
OP 695
DO 10.1523/JNEUROSCI.3827-07.2008
VO 28
IS 3
A1 Jane H.-C. Lin
A1 Nanhong Lou
A1 Ning Kang
A1 Takahiro Takano
A1 Furong Hu
A1 Xiaoning Han
A1 Qiwu Xu
A1 Ditte Lovatt
A1 Arnulfo Torres
A1 Klaus Willecke
A1 Jay Yang
A1 Jian Kang
A1 Maiken Nedergaard
YR 2008
UL http://www.jneurosci.org/content/28/3/681.abstract
AB Preconditioning is an endogenous mechanism in which a nonlethal exposure increases cellular resistance to subsequent additional severe injury. Here we show that connexin 43 (Cx43) plays a key role in protection afforded by preconditioning. Cx43 null mice were insensitive to hypoxic preconditioning, whereas wild-type littermate mice exhibited a significant reduction in infarct volume after occlusion of the middle cerebral artery. In cultures, Cx43-deficient cells responded to preconditioning only after exogenous expression of Cx43, and protection was attenuated by small interference RNA or by channel blockers. Our observations indicate that preconditioning reduced degradation of Cx43, resulting in a marked increase in the number of plasma membrane Cx43 hemichannels. Consequently, efflux of ATP through hemichannels led to accumulation of its catabolic product adenosine, a potent neuroprotective agent. Thus, adaptive modulation of Cx43 can offset environmental stress by adenosine-mediated elevation of cellular resistance.