A caspase-3-dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell-specific caspase-2 activation in the retinal cell death.

Abstract:

:This study investigates the implication of mitochondria- and caspase-dependent pathways in the death of retinal neurones exposed to the neurosteroid pregnenolone sulfate (PS) shown to evoke apoptosis and contribute to amplification and propagation of excitotoxicity. After a brief PS challenge of intact retinas, caspase-3 and caspase-2 activation and cytochrome c release occur early and independent of changes in the oxidative state measured by superoxide dismutase activity. The temporal and spatial relationship of these events suggests that a caspase-3-dependent pathway is activated in response to cytochrome c release and requires caspase-2 activation and a late cytochrome c release in specific cellular subsets of retinal layers. The protection by caspase inhibitors indicates a predominant role of the pathway in PS-induced retinal apoptosis, although a limited use of caspase inhibitors is upheld on a conceivable shift from apoptosis toward necrosis. Conversely, 3alpha-hydroxy-5beta-pregnan-20-one sulfate and 17beta-oestradiol provide complete prevention of PS-induced retinal death.

journal_name

J Neurochem

authors

Cascio C,Guarneri R,Russo D,De Leo G,Guarneri M,Piccoli F,Guarneri P

doi

10.1046/j.1471-4159.2002.01229.x

keywords:

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

1358-71

issue

6

eissn

0022-3042

issn

1471-4159

pii

1229

journal_volume

83

pub_type

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