Date of Award
Spring 5-8-2023
Degree Type
Dissertation
Degree Name
PhD Molecular Bioscience
Department
Biology
Advisor
Sulie L. Chang, PhD
Committee Member
Marylynn Snyder, PhD
Committee Member
C.J. Urso, PhD
Committee Member
Gregory Wiedman, PhD
Committee Member
Heping Zhou, PhD
Keywords
ethanol, transient receptor potential melastatin 7, blood–brain barrier, brain microvascular endothelial cells; HIV-1; HIV-1 transgenic rat
Abstract
Ethanol (EtOH) exerts its effects through various protein targets, including transient receptor potential melastatin 7 (TRPM7) channels, which play an essential role in cellular homeostasis. We demonstrated that TRPM7 was expressed in rat brain microvascular endothelial cells (rBMVECs), the major cellular component of the blood–brain barrier (BBB). Heavy alcohol drinking is often associated with HIV infection, however mechanisms underlying alcohol-induced BBB damage and HIV proteins, are not fully understood. We utilized the HIV-1 transgenic (HIV-1Tg) rat to mimic HIV-1 patients on combination anti-retroviral therapy (cART) and demonstrated TRPM7 expression in rBMVECs was lower in adolescent HIV-1Tg rats compared to control animals, however control and HIV-1Tg rats expressed similar levels at 9 weeks, indicating persistent presence of HIV-1 proteins delayed TRPM7 expression. Binge exposure to EtOH (binge EtOH) decreased TRPM7 expression in control rBMVECs in a concentration-dependent manner, and abolished TRPM7 expression in HIV-1Tg rats. In human BMVECs (hBMVECs), TRPM7 expression was downregulated after treatment with EtOH, HIV-1 proteins, and in combination. Next, we constructed in vitro BBB models using BMVECs and found TRPM7 antagonists enhanced EtOH-mediated BBB integrity changes. Our study demonstrated alcohol decreased TRPM7 expression, whereby TRPM7 could be involved in the mechanisms underlying BBB alcohol-induced damage in HIV-1 patients on cART.
Recommended Citation
Mack, Michelle L., "Involvement of TRPM7 in Alcohol-Induced Damage of the Blood-Brain Barrier in the Presence of HIV Viral Proteins" (2023). Seton Hall University Dissertations and Theses (ETDs). 3096.
https://scholarship.shu.edu/dissertations/3096
