title: Post-mortem interval effects on the phosphorylation of signaling proteins.
abstract: 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 general amounts 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 total levels of certain proteins. The PMI effects were observed in the samples stored at both 4 degrees C and room temperature, in both frontal cortex and hippocampus. Thus, it appears that measurements (such as two-dimensional gel electrophoresis and functional assays) that rely on the phosphorylation state of proteins would be extremely sensitive to PMI.
authors.affiliation: Laboratory of Molecular Pathophysiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.forename: Todd D
authors.initials: TD
authors.lastname: Gould
authors.forename: Peixiong
authors.initials: P
authors.lastname: Yuan
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D001523:Mental Disorders / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D011506:Proteins