PMID- 11477159
OWN - NLM
STAT- MEDLINE
DCOM- 20011011
LR  - 20200914
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 16
IP  - 8
DP  - 2001 Aug
TI  - alpha-MSH decreases apoptosis in ischaemic acute renal failure in rats: possible 
      mechanism of this beneficial effect.
PG  - 1583-91
AB  - BACKGROUND: Apoptosis frequently occurs in acute renal injury but the molecular 
      mechanisms responsible for this distinct form of cell death are largely unknown. 
      Fas belongs to the tumour necrosis factor (TNF)/nerve growth factor superfamily 
      and engagement by Fas ligand induces apoptosis in various epithelial cells. To 
      investigate the role of apoptosis and associated mechanisms, we examined the 
      occurrence of apoptosis and Fas and Fas ligand expression, and the therapeutic 
      effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent 
      anti-inflammatory cytokine in an ischaemic acute renal failure (ARF) rat model. 
      We also examined neutrophil infiltration together with intercellular adhesion 
      molecule-1 (ICAM-1) expression because of their possible involvement in apoptosis 
      due to their ability to release various inflammatory cytokines and reactive 
      oxygen species. METHODS: After unilateral nephrectomy in female Sprague-Dawley 
      rats, the renal artery of the contralateral kidney was clamped for 40 min and 
      reperfused. alpha-MSH or vehicle was injected intraperitoneally immediately after 
      reperfusion and at 1, 6, or 24 h after reperfusion. The expression of Fas and Fas 
      ligand was studied by western blot analysis and semiquantitative reverse 
      transcription polymerase chain reaction (RT-PCR). Apoptosis was assessed by the 
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling 
      (TUNEL) method, and neutrophil infiltration by naphthol AS-D chloracetate 
      staining. The degree of apoptosis, neutrophil infiltration, and Fas and Fas 
      ligand, and ICAM-1 expression, as well as biochemical and histological data were 
      compared between the alpha-MSH and the vehicle-treated groups. RESULTS: 
      Intraperitoneally administered alpha-MSH significantly reduced renal injury, 
      measured by blood urea nitrogen (BUN) and creatinine and by the degree of tubular 
      necrosis (109.6+/-7.1/54.7+/-3.1 mg/dl for BUN, and 1.6+/-0.2/1.03+/-0.06 mg/dl 
      for creatinine 24 h after ischaemia) (5.4+/-0.8/2.6+/-0.3 for injury score 24 h 
      after ischaemia). Ischaemia caused an increase in Fas and Fas ligand expression 
      and was accompanied by morphological evidence of apoptosis. alpha-MSH 
      significantly reduced the degree of apoptosis, as well as Fas and Fas ligand 
      expression (mean apoptotic cell number, 41.7+/-3.5/14.2+/-2.2 per x200 field at 
      24 h after ischaemia. Fas protein expression: sham, 1409+/-159 DI (densitometric 
      index); vehicle/alpha-MSH, 2818+/-635/1306+/-321 DI at 24 h and 
      5542+/-799/2867+/-455 DI at 72 h after ischaemia. Fas ligand protein expression: 
      sham, 1221+/-181 DI; vehicle/alpha-MSH, 2590+/-85/1279+/-169 DI at 4 h, 
      4376+/-268/2432+/-369 DI at 24 h and 5200+/-648/2253.7+/-1104 DI at 72 h after 
      ischaemia). Neutrophil infiltration and ICAM-1 expression were also significantly 
      reduced in alpha-MSH group (neutrophil infiltration: vehicle/ alpha-MSH, 
      5.05+/-1.8/1.59+/-0.4) (ICAM-1 expression, vehicle/alpha-MSH 
      0.46+/-0.21/0.29+/-0.19). CONCLUSION: These results suggest that apoptosis 
      clearly contributes to tubular cell loss in ischaemia/reperfusion (I/R) injury 
      possibly by neutrophil-mediated pathways or an increase in Fas-Fas ligand 
      expression. The observed beneficial effect of alpha-MSH could be related to these 
      mechanisms.
FAU - Jo, S K
AU  - Jo SK
AD  - Department of Internal Medicine, Korea University Hospital, Seoul, Korea.
FAU - Yun, S Y
AU  - Yun SY
FAU - Chang, K H
AU  - Chang KH
FAU - Cha, D R
AU  - Cha DR
FAU - Cho, W Y
AU  - Cho WY
FAU - Kim, H K
AU  - Kim HK
FAU - Won, N H
AU  - Won NH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Faslg protein, rat)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (fas Receptor)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 581-05-5 (alpha-MSH)
SB  - IM
MH  - Acute Kidney Injury/pathology/*physiopathology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Fas Ligand Protein
MH  - Female
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Ischemia/*complications/metabolism
MH  - Kidney/pathology
MH  - Membrane Glycoproteins/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Renal Circulation
MH  - Reperfusion Injury/metabolism/pathology
MH  - alpha-MSH/*pharmacology
MH  - fas Receptor/genetics/metabolism
EDAT- 2001/07/31 10:00
MHDA- 2001/10/12 10:01
CRDT- 2001/07/31 10:00
PHST- 2001/07/31 10:00 [pubmed]
PHST- 2001/10/12 10:01 [medline]
PHST- 2001/07/31 10:00 [entrez]
AID - 10.1093/ndt/16.8.1583 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2001 Aug;16(8):1583-91. doi: 10.1093/ndt/16.8.1583.