Xiao-Ying Liu1, Li-Jing Zhang2, Zhou Chen3, Li-Bin Liu1. 1. a Department of Endocrinology , Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University , Fuzhou , China. 2. b Zhejiang Department of Pharmacology , Pharmaceutical college , Ningbo , China. 3. c Department of Pharmacology , College of Pharmacy, Fujian Medical University , Fuzhou , China.
Abstract
OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor, bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic) on amyloid-β-peptide-(25-35)-induced neurotoxicity, particularly intracellular reactive oxygen species (ROS) production and mitochondria-mediated apoptotic signaling, in a human neuroblastoma (SH-SY5Y) cell model. RESULTS: We found that exposure of SH-SY5Y cells to amyloid β peptides (Aβ25-35) resulted in a significant reduction in cell viability accompanied by increased lactate dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased superoxide dismutase (SOD) activities, all of which were reversed by co-treatment with bpV(pic). Moreover, bpV(pic) induced significant protection against Aβ25-35-induced apoptosis, and effectively suppressed mitochondria-dependent apoptotic signaling triggered by Aβ25-35. DISCUSSION: Aβ peptides are thought to cause neurodegeneration in Alzheimer's disease (AD), via the induction of free radical oxidative stress. Our results indicate that bpV(pic) provides protection against Aβ25-35-induced oxidative stress and neurotoxicity, suggesting that bpV(pic) could be a potential therapeutic candidate in the treatment of neurodegenerative diseases such as AD.
OBJECTIVES: The aim of this study was to elucidate the mechanism underlying the neuroprotective effects of the phosphatase and tensin homolog (PTEN) inhibitor, bisperoxovanadium-pic [bpV(pic)]. METHODS: We determined the effects of bpV(pic) on amyloid-β-peptide-(25-35)-induced neurotoxicity, particularly intracellular reactive oxygen species (ROS) production and mitochondria-mediated apoptotic signaling, in a humanneuroblastoma (SH-SY5Y) cell model. RESULTS: We found that exposure of SH-SY5Y cells to amyloid β peptides (Aβ25-35) resulted in a significant reduction in cell viability accompanied by increased lactate dehydrogenase (LDH) release, elevated levels of intracellular ROS, and decreased superoxide dismutase (SOD) activities, all of which were reversed by co-treatment with bpV(pic). Moreover, bpV(pic) induced significant protection against Aβ25-35-induced apoptosis, and effectively suppressed mitochondria-dependent apoptotic signaling triggered by Aβ25-35. DISCUSSION: Aβ peptides are thought to cause neurodegeneration in Alzheimer's disease (AD), via the induction of free radical oxidative stress. Our results indicate that bpV(pic) provides protection against Aβ25-35-induced oxidative stress and neurotoxicity, suggesting that bpV(pic) could be a potential therapeutic candidate in the treatment of neurodegenerative diseases such as AD.
Authors: Elvis Cuevas; Hector Rosas-Hernandez; Susan M Burks; Manuel A Ramirez-Lee; Aida Guzman; Syed Z Imam; Syed F Ali; Sumit Sarkar Journal: Metab Brain Dis Date: 2019-07-02 Impact factor: 3.584