Monitoring protein phosphatase 1 isoform levels as a marker for cellular stress.

Abstract:

:Reversible protein phosphorylation is a central mechanism regulating many biological functions, and abnormal protein phosphorylation can have a devastating impact on cellular control mechanisms, including a contributing role in neurodegenerative processes. Hence, many promising novel drug development strategies involve targeting protein phosphorylation systems. In this study, we demonstrate that various cellular stresses relevant to neurodegeneration can specifically affect the protein expression levels of protein phosphatase 1 (PP1). PP1 levels were altered upon exposure of PC12 and COS-1 cells to aluminium, Abeta peptides, sodium azide, and even heat shock. Particularly interesting, given PP1's involvement in aging and neurodegeneration, was the consistent decrease in PP1gamma(1) levels in response to stress agents. In fact, alterations in the expression levels of PP1 appear to correspond to an early response of stress induction, that is, before alterations in heat shock proteins can be detected. Our data suggest that monitoring PP1 isoform expression could constitute a useful diagnostic tool for cellular stress, possibly even neurodegeneration. Additionally, our results strengthen the rationale for signal transduction therapeutics and indicate that altering the specific activity of PP1 either directly or by targeting its regulatory proteins may be a useful therapeutic development strategy for the future.

journal_name

Neurotoxicol Teratol

authors

Amador FC,Henriques AG,da Cruz E Silva OA,da Cruz E Silva EF

doi

10.1016/j.ntt.2003.12.007

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

387-95

issue

3

eissn

0892-0362

issn

1872-9738

pii

S0892036203001806

journal_volume

26

pub_type

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