title: MSM ameliorates HIV-1 Tat induced neuronal oxidative stress via rebalance of the glutathione cycle.
abstract: HIV-1 Tat protein is a key neuropathological element in HIV associated neurogcognitive disorders (HAND); a type of cognitive syndrome thought to be at least partially mediated by increased levels of brain reactive oxygen species (ROS) and nitric oxide (NO). Methylsulfonylmethane (MSM) is a sulfur-containing compound known to reduce oxidative stress. This study was conducted to determine whether administration of MSM attenuates HIV-1 Tat induced oxidative stress in mouse neuronal cells. MSM treatment significantly decreased neuronal cell NO and ROS secretion. Further, MSM significantly reversed HIV-1 Tat mediated reductions in reduced glutathione (GSH) as well as HIV-1 Tat mediated increases in oxidized glutathione (GSSG). In addition, Tat reduced nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), a key nuclear promoter of antioxidant activity, while MSM increased its translocation to the nucleus in the presence of Tat. These results suggest that HIV-1 Tat reduces the resiliency of neuron cells to oxidative stress which can be reversed by MSM. Given the clinical safety of MSM, future preclinical in vivo studies will be required to further confirm these results in effort to validate MSM as a neuroprotectant in patients at risk of, or who are already diagnosed with, HAND.
authors.affiliation: Department of Psychiatry, Neuroimmunology Laboratory, University of South Florida, Morsani College of Medicine Tampa, FL, USA ; Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Morsani College of Medicine Tampa, FL, USA.
authors.forename: Seol-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Morsani College of Medicine Tampa, FL, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, University of South Florida, Morsani College of Medicine Tampa, FL, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida, Morsani College of Medicine Tampa, FL, USA.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.affiliation: Department of Psychiatry, Neuroimmunology Laboratory, University of South Florida, Morsani College of Medicine Tampa, FL, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Giunta
keywords: HIV; cognitive; glutathione; methylsulfonylmethane; oxidative