title: Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage.
abstract: Aluminium has been implicated in various neurodegenerative diseases but exact mechanism of action is still not known. Mitochondria being a major site of reactive oxygen species production are considered to be target of oxidative stress and it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of aluminium induced neurodegeneration. Thus, the present study was undertaken to reveal the effects of chronic aluminium exposure (10mg/kg b.wt, intragastrically for 12 weeks) on the oxidative damage to mitochondrial proteins in male albino Wistar rats. Chronic aluminium exposure resulted in decrease in the activity of mitochondrial superoxide dismutase (MnSOD) and aconitase in different regions of rat brain suggesting increased oxidative stress. This decrease in MnSOD activity in turn might be responsible for the increased protein oxidation as observed in our study. All these processes taken together may cause increased oxidative damage to mitochondrial proteins in general. By taking the advantage of recent immunochemical probe for oxidatively modified proteins, we identified MnSOD to be susceptible to oxidative damage in aluminium treated animals. The quantitative RT-PCR analysis for Lon protease, a protease involved in the removal of oxidatively modified proteins from mitochondria, showed decreased mRNA expression suggesting increased oxidative damage and decreased removal of mitochondrial proteins. The identification of specific proteins as targets of oxidative damage may provide new therapeutic measures to reverse the effects of aluminium induced neurodegeneration.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D000535:Aluminum; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase