Inverse susceptibility to oxidative death of lymphocytes obtained from Alzheimer's patients and skin cancer survivors: increased apoptosis in Alzheimer's and reduced necrosis in cancer

J Gerontol A Biol Sci Med Sci. 2012 Oct;67(10):1036-40. doi: 10.1093/gerona/glr258. Epub 2012 Feb 24.

Abstract

A paucity of cancer in individuals with Alzheimer's disease (AD) and low rates of AD in cancer survivors has been reported in epidemiological studies. Deregulation in opposite directions of biological mechanisms, such as susceptibility to cell death, might be shared in the two disorders. We analyzed lymphocytes from AD and skin cancer patients as well as healthy controls and found significantly increased vulnerability of AD lymphocytes to H(2)O(2)-induced apoptotic death and higher resistance to death of skin cancer lymphocytes, due to reduced necrosis, as compared with healthy controls by pairwise comparisons adjusted for age and sex. H(2)O(2)-induced death in lymphocytes was caspase independent and significantly reduced by PARP-1 inhibition in all three groups. These differences in the susceptibility to cell death observed for lymphocytes from AD and skin cancer patients may be one of the mechanisms that help explain the inverse correlation detected between these diseases in epidemiological studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Aging / pathology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Apoptosis / drug effects
  • Benzamides / pharmacology
  • Case-Control Studies
  • Cell Survival / drug effects
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Hydrogen Peroxide / pharmacology
  • In Vitro Techniques
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism*
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Models, Biological
  • Necrosis
  • Oxidative Stress
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • 3-aminobenzamide
  • Hydrogen Peroxide
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1