Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells.

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Abstract Text:

Uta Kunter,Soizic Daniel,Maria B Arvelo,Jean Choi,Tala Shukri,Virendra I Patel,Christopher R Longo,Salvatore T Scali,Gautam Shrikhande,Eduardo Rocha,Eva Czismadia,Christina Mottley,Shane T Grey, Floege,Christiane Ferran,

BACKGROUND: Apoptotic death of renal proximal tubular epithelial cells (RPTECs) is a feature of acute and chronic renal failure. RPTECs are directly damaged by ischemia, inflammatory, and cytotoxic mediators but also contribute to their own demise by up-regulating proinflammatory nuclear factor-kappaB (NF-kappaB)-dependent proteins. In endothelial cells, the Bcl family member A1 and the zinc finger protein A20 have redundant and dual antiapoptotic and anti-inflammatory effects. We studied the function(s) of A1 and A20 in human RPTECs in vitro. METHODS: Expression of A1 [reverse transcription-polymerase chain reaction (RT-PCR) and A20 (Northern and Western blot analysis)] in RPTECs was evaluated. A1 and A20 were overexpressed in RPTECs by recombinant adenoviral-mediated gene transfer. Their effect upon inhibitor of NFkappaB alpha (IkappaBalpha) degradation (Western blot), NF-kappaB nuclear translocation [electrophoretic mobility shift assay (EMSA)], up-regulation of intercellular adhesion molecule-1 (ICAM-1) [fluorescence-activated cell sorter (FACS)] and monocyte chemoattractant protein-1 (MCP-1) (Northern blot) and apoptosis [terminal deoxynucleotiddyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)] and FACS analysis of DNA content) was determined. RESULTS: A1 and A20 were induced in RPTECs as part of the physiologic response to tumor necrosis factor (TNF). A20, but not A1, inhibited TNF-induced NF-kappaB activation by preventing IkappaBalpha degradation, hence subsequent up-regulation of the proinflammatory molecules ICAM-1 and MCP-1. Unexpectedly, A20 did not protect RPTECs from TNF and Fas-mediated apoptosis while A1 protected against both stimuli. Coexpression of A1 and A20 in RPTECs achieved additive anti-inflammatory and antiapoptotic cytoprotection. CONCLUSION: A1 and A20 exert differential cytoprotective effects in RPTECs. A1 is antiapoptotic. A20 is anti-inflammatory via blockade of NF-kappaB. We propose that A1 and A20 are both required for optimal protection of RPTECs from apoptosis (A1) and inflammation (A20) in conditions leading to renal damage.

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Publishing Authors By Initials

U Kunter,S Daniel,MB Arvelo,J Choi,T Shukri,VI Patel,CR Longo,ST Scali,G Shrikhande,E Rocha,E Czismadia,C Mottley,ST Grey,J Floege,C Ferran,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

PUBMED ID PMID:

MEDLINE DATE:

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Kidney international

VOLUME: 68

Page Numbers: 1520-32

Journal Abbreviation: Kidney Int.

ISSN: 0085-2538

DAY: 9

MONTH: Oct

YEAR: 2005

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 323470

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells. Information

Substance Name: TNFAIP3 protein, human

Registry Number: EC 6.3.2.19

Grant and Affiliation Information for Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells.

AFFILIATION: Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL 57791-04

ACRONYM: HL

MEDLINETA: Kidney Int

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells Related Publications

• A novel function for A20 in smooth muscle cells: inhibition of activation and proliferation.
• A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism.
• A20 inhibits cytokine-induced apoptosis and nuclear factor kappaB-dependent gene activation in islets.
• A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation.
• A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis.
• A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis.
• A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.
• A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and induces regression of neointimal hyperplasia.
• Combined expression of A1 and A20 achieves optimal protection of renal proximal tubular epithelial cells.
• Expression of protective genes in human renal allografts: a regulatory response to injury associated with graft rejection.
• Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function.
• Management of acute and chronic ankle instability.
• The graft unveils its secrets: provocative therapeutic leads to protected vascularized allografts.
• The universal NF-kappaB inhibitor a20 protects from transplant vasculopathy by differentially affecting apoptosis in endothelial and smooth muscle cells.
• [Not Available.]