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

被引:30
作者
Amador, FC [1 ]
Henriques, AG [1 ]
Silva, OABDE [1 ]
Silva, EFDE [1 ]
机构
[1] Univ Aveiro, Ctr Biol Celular, P-3810193 Aveiro, Portugal
关键词
D O I
10.1016/j.ntt.2003.12.007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 PF 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 PP I either directly or by targeting its regulatory proteins may be a useful therapeutic development strategy for the future. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:387 / 395
页数:9
相关论文
共 45 条
  • [31] INVOLVEMENT OF A CALCINEURIN/INHIBITOR-1 PHOSPHATASE CASCADE IN HIPPOCAMPAL LONG-TERM DEPRESSION
    MULKEY, RM
    ENDO, S
    SHENOLIKAR, S
    MALENKA, RC
    [J]. NATURE, 1994, 369 (6480) : 486 - 488
  • [32] THE ALPHA-ISOFORM AND GAMMA-1-ISOFORM OF PROTEIN PHOSPHATASE-1 ARE HIGHLY AND SPECIFICALLY CONCENTRATED IN DENDRITIC SPINES
    OUIMET, CC
    SILVA, EFDE
    GREENGARD, P
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (08) : 3396 - 3400
  • [33] Perl D. P., 1988, MET IONS BIOL SYST, P259
  • [34] PROTEIN SERINE/THREONINE PHOSPHATASES - NEW AVENUES FOR CELL REGULATION
    SHENOLIKAR, S
    [J]. ANNUAL REVIEW OF CELL BIOLOGY, 1994, 10 : 55 - 86
  • [35] SILVA EFDE, 1995, J NEUROSCI, V15, P3375
  • [36] Protein phosphorylation and APP metabolism
    Silva, EFDE
    Silva, OABDE
    [J]. NEUROCHEMICAL RESEARCH, 2003, 28 (10) : 1553 - 1561
  • [37] INHIBITION OF PROTEIN PHOSPHATASE-1 STIMULATES SECRETION OF ALZHEIMER AMYLOID PRECURSOR PROTEIN
    SILVA, EFDE
    SILVA, OABDE
    ZAIA, CTBV
    GREENGARD, P
    [J]. MOLECULAR MEDICINE, 1995, 1 (05) : 535 - 541
  • [38] REGULATED CLEAVAGE OF ALZHEIMER BETA-AMYLOID PRECURSOR PROTEIN IN THE ABSENCE OF THE CYTOPLASMIC TAIL
    SILVA, OABDE
    IVERFELDT, K
    OLTERSDORF, T
    SINHA, S
    LIEBERBURG, I
    RAMABHADRAN, TV
    SUZUKI, T
    SISODIA, SS
    GANDY, S
    GREENGARD, P
    [J]. NEUROSCIENCE, 1993, 57 (04) : 873 - 877
  • [39] MEASUREMENT OF PROTEIN USING BICINCHONINIC ACID
    SMITH, PK
    KROHN, RI
    HERMANSON, GT
    MALLIA, AK
    GARTNER, FH
    PROVENZANO, MD
    FUJIMOTO, EK
    GOEKE, NM
    OLSON, BJ
    KLENK, DC
    [J]. ANALYTICAL BIOCHEMISTRY, 1985, 150 (01) : 76 - 85
  • [40] IMMUNOHISTOCHEMICAL EVIDENCE FOR APOPTOSIS IN ALZHEIMERS-DISEASE
    SU, JH
    ANDERSON, AJ
    CUMMINGS, BJ
    COTMAN, CW
    [J]. NEUROREPORT, 1994, 5 (18) : 2529 - 2533