PMID- 16164629
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20171116
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 68
IP  - 4
DP  - 2005 Oct
TI  - Combined expression of A1 and A20 achieves optimal protection of renal proximal 
      tubular epithelial cells.
PG  - 1520-32
AB  - 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.
FAU - Kunter, Uta
AU  - Kunter U
AD  - Division of Vascular Surgery, Department of Surgery, Beth Israel Deaconess 
      Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
FAU - Daniel, Soizic
AU  - Daniel S
FAU - Arvelo, Maria B
AU  - Arvelo MB
FAU - Choi, Jean
AU  - Choi J
FAU - Shukri, Tala
AU  - Shukri T
FAU - Patel, Virendra I
AU  - Patel VI
FAU - Longo, Christopher R
AU  - Longo CR
FAU - Scali, Salvatore T
AU  - Scali ST
FAU - Shrikhande, Gautam
AU  - Shrikhande G
FAU - Rocha, Eduardo
AU  - Rocha E
FAU - Czismadia, Eva
AU  - Czismadia E
FAU - Mottley, Christina
AU  - Mottley C
FAU - Grey, Shane T
AU  - Grey ST
FAU - Floege, Jurgen
AU  - Floege J
FAU - Ferran, Christiane
AU  - Ferran C
LA  - eng
GR  - DK 063275/DK/NIDDK NIH HHS/United States
GR  - R01 HL 57791-04/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (BCL2-related protein A1)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - DNA-Binding Proteins
MH  - Epithelial Cells/cytology/*physiology
MH  - Gene Expression/physiology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kidney Tubules, Proximal/cytology/*physiology
MH  - Minor Histocompatibility Antigens
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Nephritis/pathology/physiopathology
MH  - Nuclear Proteins
MH  - Proteins/*genetics
MH  - Proto-Oncogene Proteins c-bcl-2/*genetics
MH  - RNA, Messenger/analysis
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
MH  - fas Receptor/metabolism
EDAT- 2005/09/17 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/09/17 09:00
PHST- 2005/09/17 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/09/17 09:00 [entrez]
AID - S0085-2538(15)51005-3 [pii]
AID - 10.1111/j.1523-1755.2005.00564.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Oct;68(4):1520-32. doi: 10.1111/j.1523-1755.2005.00564.x.