Effects of postmortem interval, age, and Alzheimer's disease on G-proteins in human brain

Xiaohua Li, Angela F. Greenwood, Richard Powers, Richard S. Jope

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Heterotrimeric G-proteins are Critical components in many receptor-coupled signal transduction systems, and altered levels and functions of G-proteins have been implicated in several neurological disorders, including Alzheimer's disease. Investigations in postmortem human brain provide a direct approach to study G-protein involvement in neurological disorders. Therefore, the effects of postmortem interval, aging, and Alzheimer's disease on G-protein levels were determined in postmortem human brain and an assay to measure activation of G-proteins was developed. Within the postmortem interval range of 5 to 21 h, the levels of Gαi1, Gαi2, Gαs, and Gβ were stable, whereas Gαq and Gαo decreased slightly, in human prefrontal cortex. In subjects aged 19 to 100 y, decreased levels of Gαq and Gαo were significantly correlated with increased age, but levels of tke other G-protein subunits did not vary. In Alzheimer's disease prefrontal cortext superlor temporal gyrust and occipital cortex, all G-protein subunit levels were equivalent to those in matched controls except for a slight deiicit in Gαi1. An ELISA assay using selective antibodies was used to measure [35S]GTPγS binding to Gαo and Gαi1. Binding was proportional to the concentration of OTPγS and was concentration-dependently stimulated by mastoparan equivalently in control and Alzheimer's disease prefrontal cortical membranes.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalNeurobiology of aging
Volume17
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • Aging
  • Alzheimer's disease
  • G-protein
  • GTP-binding
  • Human brain

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

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