Apoptotic response and cell cycle transition in ataxia telangiectasia cells exposed to oxidative stress.
The recently identified ATM gene plays a role in a signal transduction network activating multiple cellular functions in response to DNA damage. An attractive hypothesis is that the ATM protein is involved in a specialized antioxidant system responsible for detoxifying reactive oxygen intermediate and that the absence or dysfunction of this protein in AT cells would render them less capable of dealing with oxidative stress. In order to investigate the role of the ATM gene in cell cycle control and programmed cell death, Lymphoblastoid cell lines derived from four Ataxia-Telangiectasia (AT) patients and six controls have been analyzed. All cell lines were incubated with 2-deoxy-D-ribose (dRib), a reducing sugar that induces apoptosis through oxidative stress. The result showed an impaired response to dRib-induced apoptosis in AT cells, as well as a defect of cellular cycle arrest in G1/S phase and a normal expression of p53 protein. This indicate that the kinase activity of ATM gene product plays a very important role in the cellular response to oxidative stress. In conclusion the altered response of AT cells to oxidative stress and particularly their resistance to apoptotic cell death, could explain the high predisposition of these cells to progress toward malignant transformation.
Formichi
P
P
U.O. Neurometabolic Diseases, Institute of Neurological Sciences, University of Siena, Italy.
Battisti
C
C
Tripodi
S A
SA
Tosi P
Federico
A
A
D000293:Adolescent; D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000378:metabolism / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002648:Child; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins; D003855:Deoxyribose / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D003855:Deoxyribose; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases