Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease - PubMed (original) (raw)

Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease

Giovanna Cenini et al. J Cell Mol Med. 2008 Jun.

Abstract

Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. The tumor suppressor and transcription factor p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. Apoptosis contributes to neuronal death in many neurological disorders, including AD. In this study, we investigated p53 expression in a specific region of the cerebral cortex, namely the inferior parietal lobule (IPL), in MCI and AD brain, to test the hypothesis that alterations of this pro-apoptotic protein may be involved in neuronal death in the progression of AD. By immunoprecipitation assay, we also investigated whether 4-hydroxy-2-transnonenal (HNE), an aldehydic product of lipid peroxidation, was bound in excess to p53 in IPL from subjects with MCI and AD compared to control. Overall, the data provide evidence that p53 is involved in the neuronal death in both MCI and AD, suggesting that the observed alterations are early events in the progression of AD. In addition, HNE may be a novel non-protein mediator of oxidative stress-induced neuronal apoptosis.

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Figures

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(A) and (B) represent blots of the levels of p53 in the IPL from MCI, AD and control, respectively.(C) and (D) represent densitometric analysis of (A) and (B), respectively. Equal amounts of protein (75 mg/lane) were electrophoresed using SDS-PAGE. Proteins were transferred to nitrocellulose membranes and probed with the primary anti-p53 antibody. (A) is a representative blot of data obtained from seven control and MCI samples, and (B) is a representative blot of data obtained from five control and AD samples, respectively. The control value was set to 100%, to which experimental values were compared.*P < 0.04;AD, #P < 0.015.

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(A) and (B) represent blots of p53-HNE adduction studied from MCI, AD and control, respectively.(C) and (D) represent densitometric analysis of (A) and (B), respectively. Equal amount of protein (150 mg/lane) were immunoprecipitated by anti-p53 antibody, and immunoprecipitates were analyzed for HNE immunoreactivity by Western blotting.(A) is a representative blot of data obtained from seven control and MCI samples, and (B) is representative blot of data obtained from five control and AD samples, respectively. The control value was set to 100%, to which experimental values were compared. AD, #P < 0.004.

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