ArticleAIDS (London, England)2010
HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells.
Article in AIDS (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Oxidative Stress in HIV-Associated Neurodegeneration: Mechanisms of Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2025Review
- ROS Chronicles in HIV Infection: Genesis of Oxidative Stress, Associated Pathologies, and Therapeutic Strategies.Current issues in molecular biology · 2024Review
- An Update on Viral Infection-Associated Collapsing Glomerulopathy.Advances in kidney disease and health · 2024Review
- Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development.Kidney international · 2023Article
- Similarities and Differences between COVID-19-Associated Nephropathy and HIV-Associated Nephropathy.Kidney diseases (Basel, Switzerland) · 2022Review
- Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway.Pharmaceutical biology · 2021Article
- A Step Closer to the "Fourth 90": A Practical Narrative Review of Diagnosis and Management of Nutritional Issues of People Living with HIV.Diagnostics (Basel, Switzerland) · 2021Review
- Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.BMC nephrology · 2021Article
- ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer.Cells · 2021Review
- Epithelial proliferation and cell cycle dysregulation in kidney injury and disease.Kidney international · 2021Review
- Inhibition of apoptosis signal-regulating kinase 1 mitigates the pathogenesis of human immunodeficiency virus-associated nephropathy.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
- Mechanisms of Proteinuria in HIV.Frontiers in medicine · 2021Review
- An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy.Disease models & mechanisms · 2020Article
- The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms.Scientific reports · 2019Article
- Role of MAPK/MNK1 signaling in virus replication.Virus research · 2018Review
- Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.Journal of virology · 2018Article
- Molecular Mechanisms of Injury in HIV-Associated Nephropathy.Frontiers in medicine · 2018Review
- Impact of APOL1 polymorphism and IL-1β priming in the entry and persistence of HIV-1 in human podocytes.Retrovirology · 2016Article
- Bacterial DNA Protects Monocytic Cells against HIV-Vpr-Induced Mitochondrial Membrane Depolarization.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The Role of MicroRNAs in Kidney Disease.Non-coding RNA · 2015Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease in persons with HIV/AIDS and is characterized by focal glomerulosclerosis and dysregulated renal tubular epithelial cell (RTEC) proliferation and apoptosis. HIV-1 viral protein r (Vpr) has been implicated in HIV-induced RTEC apoptosis but the mechanisms of Vpr-induced RTEC apoptosis are unknown. The aim of this study was therefore to determine the mechanisms of Vpr-induced apoptosis in RTEC.
methodsApoptosis and caspase activation were analyzed in human RTEC (HK2) after transduction with Vpr-expressing and control lentiviral vectors. Bax and BID were inhibited with lentiviral shRNA, and ERK activation was blocked with the MEK1,2 inhibitor, U0126.
resultsVpr induced apoptosis as indicated by caspase 3/7 activation, PARP-1 cleavage and mitochondrial injury. Vpr activated both caspases-8 and 9. Inhibition of Bax reduced Vpr-induced apoptosis, as reported in other cell types. Additionally, Vpr-induced cleavage of BID to tBID and suppression of BID expression prevented Vpr-induced apoptosis. Since sustained ERK activation can activate caspase-8 in some cell types, we studied the role of ERK in Vpr-induced caspase-8 activation. Vpr induced sustained ERK activation in HK2 cells and incubation with U0126 reduced Vpr-induced caspase-8 activation, BID cleavage and apoptosis. We detected phosphorylated ERK in RTEC in HIVAN biopsy specimens by immunohistochemistry.
conclusionsThese studies delineate a novel pathway of Vpr-induced apoptosis in RTEC, which is mediated by sustained ERK activation, resulting in caspase 8-mediated cleavage of BID to tBID, thereby facilitating Bax-mediated mitochondrial injury and apoptosis.
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