Aluminium-induced oxidative DNA damage recognition and cell-cycle disruption in different regions of rat brain.
The present study was undertaken to reveal the effects of chronic aluminium exposure (10 mg/kg/b.wt, intragastrically for 12 weeks) on the oxidative DNA damage and its implication on the expression of p53 and other cell-cycle regulatory proteins in male Wister rats. Chronic aluminium exposure resulted in increased formation of 8-hydoxydeoxyguanosine in the mitochondrial DNA isolated from different regions of rat brain. The agarose gel electrophoresis revealed the DNA fragmentation pattern in aluminium-treated rat brain regions. Increased expression of p53 demonstrated that aluminium induces DNA damage. Western blot and mRNA expression analysis demonstrated increased expression of cyclin D1, suggesting disruption of cell cycle. The immunohistochemical studies showed nuclear localization of p53; however, the localization of cyclin D1 was both cytoplasmic and nuclear in aluminium-treated rat brain regions. Thus, the findings of the present study reveal that aluminium-induced oxidative damage to DNA may be involved in the neurodegeneration via increase in p53 expression and activation of cell cycle.
Kumar
Vijay
V
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Bal
Amanjit
A
Gill
Kiran Dip
KD
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007441:Intubation, Gastrointestinal; D007773:Lactates / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D017607:Aluminum Compounds; C530106:Ccnd1 protein, rat; D004272:DNA, Mitochondrial; D007773:Lactates; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C104223:aluminum lactate