The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons.

Authors:
Sisi Liu
Sisi Liu
Huazhong University of Science and Technology
China
Yanyan Xing
Yanyan Xing
Key Laboratory of State Administration of Traditional Chinese Medicine
Junbing Wang
Junbing Wang
Beijing Sino-German Union Cosmetic Institute Co.
China
Rui Pan
Rui Pan
Medical College of Jinan University
China
Guangming Li
Guangming Li
Toronto General Hospital
Canada
Guiling Chen
Guiling Chen
Suncun Hospital of Shandong Xinwen Mining Group
Liang Yan
Liang Yan
Hong Hui Hospital
New London | United States

Neurochem Res 2019 Apr 20. Epub 2019 Apr 20.

Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of 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.

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http://dx.doi.org/10.1007/s11064-019-02788-3DOI Listing
April 2019

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