HIV-1 Tat and Cocaine Impair Survival of Cultured Primary Neuronal Cells via a Mitochondrial Pathway.

Autor: De Simone FI; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.; Shriners Hospitals Pediatric Research Center, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Darbinian N; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.; Shriners Hospitals Pediatric Research Center, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Amini S; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.; Department of Biology, College of Science and Technology, Temple University, 1803 N. Broad Street, Philadelphia, PA, 19122, USA., Muniswamy M; Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., White MK; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Elrod JW; Center for Translational Medicine, Department of Pharmacology, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Datta PK; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Langford D; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA., Khalili K; Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA. kamel.khalili@temple.edu.
Jazyk: angličtina
Zdroj: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2016 Jun; Vol. 11 (2), pp. 358-68. Date of Electronic Publication: 2016 Mar 31.
DOI: 10.1007/s11481-016-9669-6
Abstrakt: Addictive stimulant drugs, such as cocaine, are known to increase the risk of exposure to HIV-1 infection and hence predispose towards the development of AIDS. Previous findings suggested that the combined effect of chronic cocaine administration and HIV-1 infection enhances cell death. Neuronal survival is highly dependent on the health of mitochondria providing a rationale for assessing mitochondrial integrity and functionality following cocaine treatment, either alone or in combination with the HIV-1 viral protein Tat, by monitoring ATP release and mitochondrial membrane potential (ΔΨm). Our results indicate that exposing human and rat primary hippocampal neurons to cocaine and HIV-1 Tat synergistically decreased both mitochondrial membrane potential and ATP production. Additionally, since previous studies suggested HIV-1 infection alters autophagy in the CNS, we investigated how HIV-1 Tat and cocaine affect autophagy in neurons. The results indicated that Tat induces an increase in LC3-II levels and the formation of Parkin-ring-like structures surrounding damaged mitochondria, indicating the possible involvement of the Parkin/PINK1/DJ-1 (PPD) complex in neuronal degeneration. The importance of mitochondrial damage is also indicated by reductions in mitochondrial membrane potential and ATP content induced by HIV-1 Tat and cocaine.
Competing Interests: F.I. De Simone declares that she has no conflict of interest. N. Darbinian declares that she has no conflict of interest. S. Amini declares that she has no conflict of interest. M.K. White declares that he has no conflict of interest. J. Elrod declares that he has no conflict of interest. P. Datta declares that he has no conflict of interest. D. Langford declares that she has no conflict of interest. K. Khalili declares that he has no conflict of interest.
Databáze: MEDLINE
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