Induction of apoptosis is triggered by the release of mitochondrial molecul
es, followed by the activation of proteases and endonucleases. In this mole
cular pathway, the activation of proteases known as caspases is thought to
be the no-return step of apoptosis. Activation of endonucleases is believe
to have a degradative function and to occur downstream of proteases. In neu
ral apoptosis occurring during embryonic development of the chick retina an
d in lens cell terminal differentiation, we have shown the activation of an
acid DNase. The molecular study of this enzyme, present in many tissues, h
as shown that it is synthesized as a serpin, the leukocyte elastase inhibit
or, a molecule displaying an anti-protease activity. After induction of apo
ptosis a post-translational modification of LEI gives rise to L-DNase IT, a
protein devoid of antiprotease activity but with an endonuclease activity.
It is then possible that after induction of apoptosis the L-LEI-DNase II p
athway acts as a switch triggering, at the same time, the activation of end
onucleases by the appearance of L-DNase II in the cell, and the activation
of protease by releasing their inhibition. In this apoptotic pathway the no
-return step would be located at the LEI-L-DNase II transition, instead of
been at the caspase level.