机构:[1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China[2]Department of Orthopedics, The First Affiliated Hospital, Medical College of Jinan University, Guangzhou, Guangdong Province, China[3]Guangdong‑Hongkong‑Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China
HIV-1 gp120, an important subunit of the envelope spikes that decorate the surface of virions, is known to play a vital role in neuronal injury during HIV-1-associated neurocognitive disorder (HAND), although the pathological mechanism is not fully understood. Our previous studies have suggested that the V3 loop of HIV-1 gp120 (HIV-1 gp120 V3 loop) can induce neuronal apoptosis in the hippocampus, resulting in impairment in spatial learning and memory in Sprague-Dawley (SD) rats. In this study, we demonstrated that autophagy was significantly increased in rat primary hippocampal neurons in response to treatment of HIV-1 gp120 V3 loop. Importantly, HIV-1 gp120 V3 loop-induced autophagy played a dual role in the cell survival and death. An increase in autophagy for a short period inhibited apoptosis of neurons, while persistent autophagy over an extended period of time played a detrimental role by augmenting the apoptotic cascade in rat primary hippocampal neurons. In addition, we found that the HIV-1 gp120 V3 loop induced autophagy via AMPK/mTOR-dependent and calpain/mTOR-independent pathways, and the ERK/mTOR pathway plays a partial role. These findings provide evidence that HIV-1-induced autophagy plays a dual role in the survival and apoptosis of the primary rat hippocampal neurons and persistent autophagy may contribute to the pathogenesis of HAND, and autophagy modulation may represent a potential therapeutic strategy for reducing neuronal damage in HAND.
基金:
Grants from
the National Natural Science Foundation of China (81171134 and
81471235), Guangdong Provincial Natural Science Foundation of
China (2014A030313360), the Program of Introducing Talents of Discipline
to Universities (B14036), the Science and Technology Foundation
of Guangdong (2010B030700016), and the cultivation and innovation
fund of Jinan University (No. 21617460).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2018]版:
大类|3 区医学
小类|4 区生化与分子生物学4 区神经科学
最新[2025]版:
大类|3 区医学
小类|3 区生化与分子生物学3 区神经科学
第一作者:
第一作者机构:[1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China[3]Guangdong‑Hongkong‑Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China
推荐引用方式(GB/T 7714):
Liu Sisi,Xing Yanyan,Wang Junbing,et al.The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons.[J].Neurochemical research.2019,44(7):1636-1652.doi:10.1007/s11064-019-02788-3.
APA:
Liu Sisi,Xing Yanyan,Wang Junbing,Pan Rui,Li Guangming...&Dong Jun.(2019).The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons..Neurochemical research,44,(7)
MLA:
Liu Sisi,et al."The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons.".Neurochemical research 44..7(2019):1636-1652