Connexin Mediates Gap Junction-independent Resistance to Cellular Injury

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Jan 21

PMID 12533603

Citations 54

Authors

Jane H-C Lin

Jay Yang

Shujun Liu

Takahiro Takano

Xiaohai Wang

Qun Gao

Klaus Willecke

Maiken Nedergaard

Affiliations

Soon will be listed here.

Abstract

Although gap junctions regulate essential processes during development and differentiation, the role of gap junctions in cell death is poorly understood. We demonstrate here that the forced expression of connexin 43 (Cx43), the main constituent of astrocytic gap junctions, protected against cell injury with a potency that was comparable with that from the expression of the proto-oncogene bcl2. The expression of two other members of the Cx family, Cx32 and Cx40, also increased the resistance to injury from exposures to calcium overload, oxidative stress, metabolic inhibition, tamoxifen, and UV irradiation, but not against staurosporine- and dexamethasone-mediated death. Surprisingly, the anti-death activity of connexin proteins was independent of gap junction channel function, because physical isolation or the pharmacological inhibition of coupling did not significantly increase cell death. Moreover, cells expressing nonfunctional mutant connexins also acquired a high resistance to injury. These observations identify Cx proteins as active players in cell survival.

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