RGD Reference Report - AMPK activator AICAR ameliorates ischaemia reperfusion injury in the rat kidney. - Rat Genome Database

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AMPK activator AICAR ameliorates ischaemia reperfusion injury in the rat kidney.

Authors: Lempiainen, J  Finckenberg, P  Levijoki, J  Mervaala, E 
Citation: Lempiainen J, etal., Br J Pharmacol. 2012 Jul;166(6):1905-15. doi: 10.1111/j.1476-5381.2012.01895.x.
RGD ID: 9495930
Pubmed: PMID:22324445   (View Abstract at PubMed)
PMCID: PMC3402813   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1476-5381.2012.01895.x   (Journal Full-text)

BACKGROUND AND PURPOSE Renal ischaemia/reperfusion (RI/R) injury is a major cause of acute kidney injury (AKI) and an important determinant of long-term kidney dysfunction. AMP-kinase and histone deacetylase sirtuin 1 (SIRT1) regulate cellular metabolism and are activated during hypoxia. We investigated whether AMP-kinase activator AICAR (5-amino-4-imidazolecarboxamide riboside-1-beta-D-ribofuranoside) ameliorates RI/R injury and whether SIRT1 is involved in the pathogenesis. EXPERIMENTAL APPROACH Eight-week-old Sprague Dawley rats were divided into five groups: (i) sham-operated group; (ii) I/R group (40 min bilateral ischaemia followed by 24 h of reperfusion; (iii) I/R group + AICAR 50 mg.kg(-1) i.v. given 60 min before operation; (iv). I/R group + AICAR 160 mg.kg(-1) i.v; (v) I/R group + AICAR 500 mg.kg(-1) i.v. Serum creatinine and urea levels were measured. Acute tubular necrosis (ATN), monocyte/macrophage infiltration and nitrotyrosine expression were scored. Kidney AMP-activated protein kinase (AMPK) and SIRT1 expressions were measured. KEY RESULTS Highest dose of AICAR decreased serum creatinine and urea levels, attenuated I/R injury-induced nitrosative stress and monocyte/macrophage infiltration, and ameliorated the development of ATN. Kidney I/R injury was associated with decreased AMPK phosphorylation and a fivefold increase in kidney SIRT1 expression. AICAR increased pAMPK/AMPK ratio and prevented the I/R-induced increase in renal SIRT1 expression. CONCLUSIONS AND IMPLICATIONS AICAR protects against the development of ATN after kidney I/R injury. Activators of kidney AMP kinase may thus represent a novel therapeutic approach to patients susceptible to AKI and to those undergoing kidney transplantation. The present study also suggests a role for SIRT1 in the pathogenesis of RI/R injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Kidney Reperfusion Injury treatmentISOSirt1 (Rattus norvegicus)9495930; 9495930 RGD 
Kidney Reperfusion Injury treatmentIEP 9495930 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sirt1  (sirtuin 1)

Genes (Mus musculus)
Sirt1  (sirtuin 1)

Genes (Homo sapiens)
SIRT1  (sirtuin 1)


Additional Information