title: Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury.
abstract: HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat(1-72)-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Stevens
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Gawryluk
authors.forename: Liang
authors.initials: L
authors.lastname: Hui
authors.forename: Xuesong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Basic Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline St., Grand Forks, North Dakota 58203, USA. jonathan.geiger@med.und.edu.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Geiger
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003401:Creatine / Q000378:metabolism*; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D053858:Metabolic Networks and Pathways; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology* / Q000821:virology; D018696:Neuroprotective Agents / Q000378:metabolism*; D010084:Oxidation-Reduction; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D054322:tat Gene Products, Human Immunodeficiency Virus; D003401:Creatine