دورية أكاديمية
أعرض في EDS

HIV-1 Tat-induced bystander apoptosis in Jurkat cells involves unfolded protein responses.

التفاصيل البيبلوغرافية
العنوان: HIV-1 Tat-induced bystander apoptosis in Jurkat cells involves unfolded protein responses.
المؤلفون: Campestrini J; Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil., Silveira DB; Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil., Pinto AR; Laboratório de Imunologia Aplicada, Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
المصدر: Cell biochemistry and function [Cell Biochem Funct] 2018 Oct; Vol. 36 (7), pp. 377-386. Date of Electronic Publication: 2018 Sep 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 8305874 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-0844 (Electronic) Linking ISSN: 02636484 NLM ISO Abbreviation: Cell Biochem Funct Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, England : Wiley-Blackwell
Original Publication: Guildford, Surrey : Butterworth Scientific Ltd., c1983-
مواضيع طبية MeSH: Apoptosis* , Bystander Effect* , Unfolded Protein Response*, tat Gene Products, Human Immunodeficiency Virus/*metabolism, CD4-Positive T-Lymphocytes/immunology ; Cell Survival ; Cells, Cultured ; Endoplasmic Reticulum Stress/immunology ; HIV/immunology ; Humans ; Jurkat Cells ; Protein Unfolding
مستخلص: The HIV transactivator protein (Tat) is a multifunctional protein that plays a critical role in viral replication and contributes to several pathological symptoms of HIV-1 infection, which has the loss of CD4+ T lymphocytes as one of its hallmark features. It has been shown that endoplasmic reticulum (ER) stress, including viral infections, is implicated in cellular dysfunction and cell death through activation of the unfolded protein response (UPR). Here, we demonstrate that the bystander stimulus of Tat on Jurkat cells resulted in time-dependent overexpression of major UPR markers including ER chaperone BiP, ER stress sensors ATF6, PERK, and IRE1, as well as an increase in levels of downstream mediators eIF2α, ATF4, XBP-1, and proapoptotic factors CHOP, GADD34, and BIM. This upregulation of UPR mediators was accompanied by decreased cell viability and increased apoptosis as evidenced by blue trypan dye exclusion and flow cytometry assays, respectively. Furthermore, we found that the Tat-associated apoptosis of Jurkat cells led to the loss of mitochondrial membrane potential and caspase-12 and -3 activation. Taken together, these results suggest that the exposure of HIV-1 Tat leads to ER stress/UPR triggering which in turn contributes to apoptotic death in Jurkat cells. SIGNIFICANCE OF THE STUDY: In the present work, we provide a substantial insight into the link between ER impairment and apoptotic death following a bystander HIV Tat stimulus, revealing an underlying ER-mediated apoptotic mechanism which could explain the continuous depletion of uninfected CD4+ T lymphocytes observed in HIV-related disease. Our findings reinforce the relevance of ER stress molecular responses in the course of HIV infection and may afford valuable information for the development of new therapeutic strategies to avoid CD4+ T lymphocyte loss and other disorders induced by circulant Tat.
(© 2018 John Wiley & Sons, Ltd.)
معلومات مُعتمدة: CNPq; CAPES
فهرسة مساهمة: Keywords: ER stress; HIV Tat; Jurkat cells; UPR pathway; apoptosis
المشرفين على المادة: 0 (tat Gene Products, Human Immunodeficiency Virus)
تواريخ الأحداث: Date Created: 20180925 Date Completed: 20181025 Latest Revision: 20181025
رمز التحديث: 20240628
DOI: 10.1002/cbf.3357
PMID: 30246458
قاعدة البيانات: MEDLINE
الوصف
تدمد:1099-0844
DOI:10.1002/cbf.3357