Post-mortem interval effects on the phosphorylation of signaling proteins

被引：71

作者：

Jianlin Li

Todd D Gould

Peixiong Yuan

Husseini K Manji

Guang Chen

机构：

[1] Laboratory of Molecular Pathophysiology, Wayne State University School of Medicine, Detroit, MI

[2] Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, MD

来源：

Neuropsychopharmacology | 2003年 / 28卷 / 6期

关键词：

Alzheimer’s disease; Bipolar disorder; Depression; Protein phosphorylation; Schizophrenia; Two-dimensionalgelelectrophoresis;

D O I：

10.1038/sj.npp.1300112

中图分类号：

学科分类号：

摘要：

Post-mortem brain tissue provides a unique opportunity to uncover the genes or proteins involved in the pathophysiology of neuropsychiatric disorders. Protein phosphorylation is a common protein modification within intracellular signaling pathways that affects the distribution and function of protein, and has been hypothesized to be of major importance in both the pathophysiology and treatment of major neuropsychiatric disorders. Thus, we were interested in ascertaining the stability of the phosphorylated forms of proteins that are involved in cellular signaling. Antibodies against phospho-tyrosine, phospho-threonine, and phospho-PKA substrates were used to examine the PMI effects on the generalamounts of proteins in their phosphorylated form. Phospho-specific antibodies for ERK, JNK, RSK, CREB, and ATF-2 were used to test the effects of PMI on specific proteins whose functioning are known to be regulated markedly by phosphorylation. We found that PMI rapidly decreased the levels of proteins in their phosphorylated states and also decreased the totallevels of certain proteins. The PMI effects were observed in the samples stored at both 4°C and room temperature, in both frontalcortex and hippocampus. Thus, it appears that measurements (such as two-dimensionalgelelectrophoresis and functional assays) that rely on the phosphorylation state of proteins would be extremely sensitive to PMI. © 2003 Nature Publishing Group.

引用

页码：1017 / 1025

页数：8

共 60 条

[1] Akil M., Lewis D.A., The distribution of tyrosine hydroxylase-immunoreactive fibers in the human entorhinal cortex, Neu-Roscience, 60, pp. 857-874, (1994)
[2] Barton A.J., Pearson R.C., Najlerahim A., Harrison P.J., Pre- and postmortem influences on brain RNA, J. Neurochem, 61, pp. 1-11, (1993)
[3] Bowen D.M., Smith C.B., White P., Davison A.N., Neurotrans-mitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies, Brain, 99, pp. 459-496, (1976)
[4] Bradford M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal Biochem, 72, pp. 248-254, (1976)
[5] Bucht G., Adolfsson R., Gottfries C.G., Roos B.E., Winblad B., Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian Variation, J. Neural Transm, 51, pp. 185-203, (1981)
[6] Burack M.A., Halpain S., Site-specific regulation of Alzhei-mer-like tau phosphorylation in living neurons, Neuroscience, 72, pp. 167-184, (1996)
[7] Burke W.J., O'Malley K.L., Chung H.D., Harmon S.K., Miller Jp Berg L., Effect of pre- and postmortem variables on specific mRNA levels in human brain, Brain Res Mol Brain Res, 11, pp. 37-41, (1991)
[8] Butterworth J., Yates C.M., Simpson J., Phosphate-activated glutaminase in relation to Huntington’s disease and agonal state, J. Neurochem, 41, pp. 440-447, (1983)
[9] Carlsson A., Svennerholm L., Winblad B., Seasonal and circadian monoamine variations in human brains examined post mortem, Actapsychiatrscand, 280, pp. 75-85, (1980)
[10] Dodd P.R., Hambley J.W., Cowburn R.F., Hardy J.A., A comparison of methodologies for the study of functional transmitter neurochemistry in human brain, J. Neurochem, 50, pp. 1333-1345, (1988)

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