Monitoring protein phosphatase 1 isoform levels as a marker for cellular stress.
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.
Amador
Fátima Camões
FC
Centro de Biologia Celular, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
Henriques
Ana Gabriela
AG
da Cruz E Silva
Odete A B
OA
da Cruz E Silva
Edgar F
EF
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology; D008991:Monitoring, Physiologic; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D054645:Protein Phosphatase 1; D051381:Rats; D019810:Sodium Azide / Q000633:toxicity; D013312:Stress, Physiological / Q000175:diagnosis / Q000378:metabolism*; D013995:Time; D013997:Time Factors
D017607:Aluminum Compounds; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002712:Chlorides; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D000077410:Aluminum Chloride; D019810:Sodium Azide; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1