QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uberti, D. Articles by Memo, M. Search for Related Content PubMed PubMed Citation Articles by Uberti, D. Articles by Memo, M. Social Bookmarking                         What's this?

Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer's disease patients

¹ Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy
² Department of Pathology, University of Brescia, Brescia, Italy
³ Department of Experimental and Applied Pharmacology, University of Pavia, Pavia, Italy

^* Author for correspondence (e-mail: memo{at}med.unibs.it )

Accepted 16 May 2002

In this study, we evaluated the response of different human skin fibroblast cultures obtained from eight probable Alzheimer's disease patients and eight non-Alzheimer's disease subjects to an acute oxidative injury elicited by H₂O₂. This treatment generates reactive oxygen species, which are responsible for DNA damage and apoptosis. To compare the sensitivity of fibroblasts from Alzheimer's disease or non-Alzheimer's disease patients to H₂O₂ exposure, we evaluated different parameters, including cell viability, the extension of DNA damage and the ability of the cells to arrest proliferation and to activate an apoptotic program. We found that fibroblasts from Alzheimer's disease patients were more resistant that those from control subjects to H₂O₂ treatment, although the extent of DNA damage induced by the oxidative injury was similar in both experimental groups. The protective mechanism of Alzheimer's disease fibroblasts was related to an impairment of H₂O₂-induced cell cycle arrest and characterized by an accelerated re-entry into the cell cycle and a diminished induction of apoptosis. Fibroblasts from Alzheimer's disease patients also have a profound impairment in the H₂O₂-activated, p53-dependent pathway, which results in a lack of activation of p53 or p53-target genes, including p21, GADD45 and bax. This study demonstrates a specific alteration of an intracellular pathway involved in sensing and repairing DNA damage in peripheral cells from Alzheimer's disease patients.

Key words: DNA damage, Human, Cell cycle, Reactive oxygen species, p21, GADD45, Bax

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Impaired p53 pathway in Alzheimer's

JCS 2002 115: 1505. [Full Text]  

This article has been cited by other articles:

				X. Wang, B. Su, H. Fujioka, and X. Zhu Dynamin-Like Protein 1 Reduction Underlies Mitochondrial Morphology and Distribution Abnormalities in Fibroblasts from Sporadic Alzheimer's Disease Patients Am. J. Pathol., August 1, 2008; 173(2): 470 - 482. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

				L. Qu, S. Huang, D. Baltzis, A.-M. Rivas-Estilla, O. Pluquet, M. Hatzoglou, C. Koumenis, Y. Taya, A. Yoshimura, and A. E. Koromilas Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3{beta} Genes & Dev., February 1, 2004; 18(3): 261 - 277. [Abstract] [Full Text] [PDF]