title: 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.
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.
authors.affiliation: Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile. mbehrens@redclinicauchile.cl
authors.forename: Maria I
authors.initials: MI
authors.lastname: Behrens
authors.forename: Monica
authors.initials: M
authors.lastname: Silva
authors.forename: Felipe
authors.initials: F
authors.lastname: Salech
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Ponce
authors.forename: Daniela
authors.initials: D
authors.lastname: Merino
authors.forename: Mariana
authors.initials: M
authors.lastname: Sinning
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009336:Necrosis; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1