Identification of the Differentially Expressed Genes Involved in the Synergistic Neurotoxicity of an HIV Protease Inhibitor and Methamphetamine

Sangsang Li; Yanfei Li; Bingpeng Deng; Jie Yan; Yong Wang

doi:10.2174/1570162X17666190924200354

Identification of the Differentially Expressed Genes Involved in the Synergistic Neurotoxicity of an HIV Protease Inhibitor and Methamphetamine

Curr HIV Res. 2019;17(4):290-303. doi: 10.2174/1570162X17666190924200354.

Authors

Sangsang Li^{1

2}, Yanfei Li^{1

2}, Bingpeng Deng¹, Jie Yan¹, Yong Wang¹

Affiliations

¹ Department of Forensic Science, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
² Department of Immunology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

PMID: 31550215
DOI: 10.2174/1570162X17666190924200354

Abstract

Background: The abuse of psychostimulants such as methamphetamine (METH) is common in human immunodeficiency virus (HIV)-infected individuals. Acquired immunodeficiency syndrome (AIDS) patients taking METH and antiretroviral drugs could suffer severe neurologic damage and cognitive impairment.

Objective: To reveal the underlying neuropathologic mechanisms of an HIV protease inhibitor (PI) combined with METH, growth-inhibition tests of dopaminergic cells and RNA sequencing were performed.

Methods: A combination of METH and PI caused more growth inhibition of dopaminergic cells than METH alone or a PI alone. Furthermore, we identified differentially expressed gene (DEG) patterns in the METH vs. untreated cells (1161 genes), PI vs. untreated cells (16 genes), METH-PI vs. PI (3959 genes), and METH-PI vs. METH groups (14 genes).

Results: The DEGs in the METH-PI co-treatment group were verified in the brains of a mouse model using quantitative polymerase chain reaction and were involved mostly in the regulatory functions of cell proliferation and inflammation.

Conclusion: Such identification of key regulatory genes could facilitate the study of their neuroprotective potential in the users of METH and PIs.

Keywords: AIDS; HIV protease inhibitor; Methamphetamine; RNA-seq; differentially expressed gene; synergistic neurotoxicity..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acquired Immunodeficiency Syndrome / drug therapy
Acquired Immunodeficiency Syndrome / genetics
Acquired Immunodeficiency Syndrome / virology
Animals
Cell Line, Tumor
Central Nervous System Stimulants / adverse effects*
Computational Biology / methods
Disease Models, Animal
Drug Synergism
Gene Expression Profiling
Gene Expression Regulation / drug effects*
Gene Ontology
HIV Infections / drug therapy
HIV Infections / genetics
HIV Infections / virology
HIV Protease Inhibitors / adverse effects*
Humans
Male
Methamphetamine / adverse effects*
Mice

Substances

Central Nervous System Stimulants
HIV Protease Inhibitors
Methamphetamine