Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages

过氧亚硝酸盐分解催化剂可防止与 HIV 感染巨噬细胞上清液一起孵育的人类星形细胞瘤细胞系中的细胞凋亡

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作者:Carolina Muscoli, Daniela Salvemini, Donatella Paolino, Michelangelo Iannone, Ernesto Palma, Antonio Cufari, Domenicantonio Rotiroti, Carlo Federico Perno, Stefano Aquaro, Vincenzo Mollace

Background

Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occurring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M).

Conclusions

Taken together, our results suggest that inhibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.

Results

Flow cytometric analysis (FACS) of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite) and by abnormal formation of malondialdehyde (MDA). Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. Conclusions: Taken together, our results suggest that inhibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.

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