| HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells. | |
| | |
MedLine Citation:
|
PMID: 20404718 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: HIV-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. METHODS: Apoptosis 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. RESULTS: Vpr 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. CONCLUSIONS: These 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. |
| | |
Authors:
|
Alexandra Snyder; Zygimantas C Alsauskas; Jeremy S Leventhal; Paul E Rosenstiel; Pengfei Gong; Justin J K Chan; Kevin Barley; John C He; Mary E Klotman; Michael J Ross; Paul E Klotman |
Related Documents
:
|
16429138 - Human immunodeficiency virus 1 nef suppresses cd40-dependent immunoglobulin class switc... 17314518 - Early immune activation in gut-associated and peripheral lymphoid tissue during acute h... 19305418 - Is the high virulence of hiv-1 an unfortunate coincidence of primate lentiviral evolution? 12437858 - Anti-human immunodeficiency virus noncytolytic cd8+ t-cell response: a review. 22342458 - A1/bfl-1 in leukocyte development and cell death. 11024538 - Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide in... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: AIDS (London, England) Volume: 24 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2010 May |
Date Detail:
|
Created Date: 2010-04-27 Completed Date: 2011-03-31 Revised Date: 2011-07-28 |
Medline Journal Info:
|
Nlm Unique ID: 8710219 Medline TA: AIDS Country: England |
Other Details:
|
Languages: eng Pagination: 1107-19 Citation Subset: IM; X |
Affiliation:
|
Department of Nephrology, Mount Sinai School of Medicine, New York, New York 10029, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
AIDS-Associated Nephropathy
/
genetics,
metabolism*,
virology Apoptosis / genetics, physiology* Caspase 8 / genetics, metabolism* Cell Proliferation Extracellular Signal-Regulated MAP Kinases / metabolism* Gene Expression Regulation, Viral Gene Products, vpr / genetics, metabolism* HIV-1* Humans Kidney Failure, Chronic / genetics, metabolism*, virology Kidney Tubules / virology RNA, Viral Virus Replication |
| Grant Support | |
ID/Acronym/Agency:
|
P01 DK056492-09/DK/NIDDK NIH HHS; P01DK056492/DK/NIDDK NIH HHS; R01 DK078510-03/DK/NIDDK NIH HHS; R01 DK078510-04/DK/NIDDK NIH HHS; R01DK078510/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
|
0/Gene Products, vpr; 0/RNA, Viral; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.22.-/Caspase 8 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Validation of a translated version of the modified Japanese orthopaedic association score to assess ...
Next Document: A Novel Bioimpedance Technique to Monitor Fluid Volume State during Hemodialysis Treatment.