ArticleMolecular neurobiology2016
HIV Tat-Mediated Induction of Human Brain Microvascular Endothelial Cell Apoptosis Involves Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence.Advances in experimental medicine and biology · 2026Review
- The effect of TMAO on aging-associated cardiovascular and metabolic pathways and emerging therapies.Molecular and cellular biochemistry · 2025Review
- HIV-1 viral protein effect on cerebral microvasculature: An in vitro blood-brain barrier model.Physiological reports · 2025Article
- Methamphetamine and HIV-1 Tat Protein Synergistically Induce Endoplasmic Reticulum Stress to Promote TRIM13-Mediated Neuronal Autophagy.Molecular neurobiology · 2025Article
- HIV-Tat and vascular endothelium: implications in the HIV associated brain, heart, and lung complications.Frontiers in immunology · 2025Review
- HIV-1 Tat-induced disruption of epithelial junctions and epithelial-mesenchymal transition of oral and genital epithelial cells lead to increased invasiveness of neoplastic cells and the spread of herpes simplex virus and cytomegalovirus.Frontiers in immunology · 2025Review
- Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.Cells · 2024Review
- HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.NeuroImmune pharmacology and therapeutics · 2024Article
- Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments.Circulation research · 2024Review
- The changing landscape of HIV-associated kidney disease.Nature reviews. Nephrology · 2024Review
- Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas.Life (Basel, Switzerland) · 2024Review
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.Journal of neurovirology · 2023Review
- Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence.International journal of molecular sciences · 2023Article
- PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.Journal of neurology and psychology · 2023Article
- HIV Promotes Neurocognitive Impairment by Damaging the Hippocampal Microvessels.Molecular neurobiology · 2022Article
- Atherosclerosis in HIV Patients: What Do We Know so Far?International journal of molecular sciences · 2022Review
- Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments.International journal of molecular sciences · 2022Review
- A Non-Canonical Role for IRE1α Links ER and Mitochondria as Key Regulators of Astrocyte Dysfunction: Implications in Methamphetamine use and HIV-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Endoplasmic reticulum (ER) stress triggered under hyperglycemic, hypoxic, and oxidative conditions has been implicated in cellular dysfunction through activation of the unfolded protein response (UPR). Recent clinical studies have documented that the release of soluble cellular and host factors following HIV infection in the central nervous system (CNS) results in induction of the ER stress response. Herein, we demonstrate that exposure of human brain microvascular endothelial cells (HBMECs) to HIV transactivator protein Tat101 resulted in early induction of several major ER stress regulators including ER chaperones Bip/GRP78 and ER stress sensors ATF6, p-PERK, and downstream mediators p-eIF2α and ATF4. Upregulation of the ER stress mediators was accompanied by decreased cell viability and increased apoptosis as evidenced by MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. Pretreatment of HBMECs with either ER inhibitor or knockdown of the effector C/EBP homologous protein (CHOP) resulted in increased cell viability and abrogation of apoptosis following Tat exposure. Notably, Tat-mediated activation of the UPR response involved reactive oxygen species. Furthermore, treatment of Tat also resulted in mitochondrial dysfunction, evidenced by decrease in Bcl2/Bax ratio, dysfunction of mitochondrial membrane potential, and release of cytochrome c, all of which could be partially reversed by the ER stress inhibitor. The current study demonstrates that exposure of HBMECs to Tat induces multiple stress responses, including ER stress and mitochondrial dysfunction which in turn lead to apoptosis.
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