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Synergistic Effect and Mechanism of Apoptosis Induction by Morphine and the HIV-1gp120V3 Loop in Hippocampal Neurons.

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机构: [1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, school of Basic medical science and Public health, Jinan University, Guangzhou 510632, Guangdong Province, China [2]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, Guangdong Province, China [3]Department of Orthopedics, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong Province, China
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关键词: HIV-associated neurocognitive disorders Morphine HIV-1 gp120V3 loop ERK Hippocampal neurons Apoptosis

摘要:
HIV-associated neurocognitive disorders (HAND) are a collective name for neurological disorders associated with HIV-1 infection. The incidence and severity of HAND are increased by concomitant opioid use disorder, such as heroin and morphine abuse. Our previous study showed that the HIV-1 envelope protein gp120 and morphine synergistically induce apoptosis in rat hippocampal neurons. However, the underlying mechanism remains unclear. We hypothesized that morphine and gp120 activated the neuronal apoptosis signaling pathway via their typical membrane receptors. If they shared key signaling molecules, their induction of neuronal apoptosis could be inhibited by blocking these targets. We found that morphine and gp120V3 loop synergistically induced hippocampal neuron apoptosis, mediated by activating the extracellular signal-regulated kinase (ERK) pathway, increasing the intracellular Ca2 + concentration and expression of caspase-, and reducing the mitochondrial membrane potential. The ERK inhibitor PD98509 and the phosphatidylinositol 3-kinase activator IGF-1 blocked this effect. These results indicate that ERK plays a crucial role in the apoptosis of hippocampal neurons in HAND.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 药学 3 区 神经科学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 神经科学 3 区 药学
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第一作者机构: [1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, school of Basic medical science and Public health, Jinan University, Guangzhou 510632, Guangdong Province, China
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通讯机构: [1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, school of Basic medical science and Public health, Jinan University, Guangzhou 510632, Guangdong Province, China [2]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, Guangdong Province, China
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