Apoptotic vs. necrotic

Mark Mattson mpm at seqanal.mi.uky.edu
Tue Apr 12 09:27:39 EST 1994


It seems to me that -- although they may be ultimately different in mechanism
of killing -- way too much emphasis has been placed on drawing a distinction
between the events which TRIGGER apoptotic or necrotic deaths.  I was 
particulary struck by the futility in this argument at last year's Society
for Neuroscience meeting where I saw at least half a dozen posters lined up
next to each other, alternating in their conclusions about whether glutamate
excitotoxicity triggered necrotic or apoptotic death.  It is my opinion
that the SAME THING triggers both:  FREE RADICALS.  Obviously, free radicals
can cause the kind of membrane damage characteristic of necrosis, and more
and more evidence suggests that free radicals can trigger apoptosis.  Ex:
bcl-2 seems to prevent apoptosis by antagonizing a radical-evoked event;
several labs suggest that tumor necrosis factors (which, despite their
name, can trigger apoptosis) use reactive oxygen species in their signal
transduction pathways.  To me, the distinction seems to be a quantitative one:
if free radicals are generated in large amounts, membranes are rapidly 
damaged; if the levels of oxidation are lower, some program (perhaps, genetic 
in nature) is activated which kills the cell more slowly.  This is consistent
with the first descriptions of apoptosis in the liver, where it was caused 
by the same insult as the coincident necrosis -- the necrosis was in the 
center of the lesion and the apoptosis was on the periphery.  One can easily
imagine that this spatial delineation was caused by the decreasing concen-
trations of radicals as they diffused concentrically from the center of the
lesion.

Steven W. Barger, Ph.D.
Sanders-Brown Center on Aging




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