Nature Neuroscience
1, 494 - 500 (1998)
doi:10.1038/2210
Gap-junction-mediated propagation and amplification of cell injuryJane H-C Lin1, Helga Weigel2, Maria Luisa Cotrina2, Shujun Liu2, Earl Bueno2, Anker J. Hansen3, Thomas W. Hansen2, Steven Goldman4
& Maiken Nedergaard2, 51
Department of Pathology, New York Medical College,
Valhalla, New York 10595, USA
2
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, 10595, USA
3
NOVO Nordisk, Malev, 2750, Denmark
4
Department of Neurology and Neuroscience, Cornell University Medical Center, New York, New York 10021, USA
5
Department of Neurosurgery, New York Medical College, Valhalla, New York, 10595, USA
Correspondence should be addressed to Jane H-C Lin Jane_Lin@nymc.eduGap junctions are conductive channels that connect the interiors of coupled
cells. We determined whether gap junctions propagate transcellular signals
during metabolic stress and whether such signaling exacerbates cell injury.
Although overexpression of the human proto-oncogene bcl2 in C6 glioma cells
normally increased their resistance to injury, the relative resistance of
bcl2+ cells to calcium overload, oxidative stress and metabolic
inhibition was compromised when they formed gap junctions with more vulnerable
cells. The likelihood of death was in direct proportion to the number and
density of gap junctions with their less resistant neighbors. Thus, dying
glia killed neighboring cells that would otherwise have escaped injury. This
process of glial 'fratricide' may provide a basis for the secondary propagation
of brain injury in cerebral ischemia.
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