5'-amp-activated Protein Kinase Activation Prevents Postischemic Leukocyte-endothelial Cell Adhesive Interactions.
From: Dept. of Medical Pharmacology and Physiology, Univ. of Missouri-Columbia, 1 Hospital Dr., Columbia, MO 65212, USA. korthuisr@health.missouri.edu
American journal of physiology. Heart and circulatory physiology
- Publish Date: Jan 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 1
- Pages: H326-32
- Medium: Print
- Language: English
- Citation (JAMA): Gaskin F Spencer, Kamada Kazuhiro, Yusof Mozow, et al. 5'-amp-activated Protein Kinase Activation Prevents Postischemic Leukocyte-endothelial Cell Adhesive Interactions.. Am. J. Physiol. Heart Circ. Physiol. Jan 2007;292:H326-32
Abstract
Preconditioning (PC) with nitric oxide (NO) donors or agents that increase endothelial NO synthase (eNOS) activity 24 h before ischemia-reperfusion (I/R) prevents postischemic leukocyte rolling (LR) and stationary leukocyte adhesion (LA). Since 5’-AMP-activated protein kinase (AMPK) phosphorylates eNOS at Ser1177, resulting in activation, we postulated that AMPK activation may trigger the development of a preconditioned anti-inflammatory phenotype similar to that induced by NO donors. Wild-type (WT) C57BL/6J and eNOS(-/-) mice were treated with the AMPK agonist 5-aminoimidazole-4-carboxamide 1-beta-d-furanoside (AICAR) 30 min (early AICAR PC) or 24 h (late AICAR PC) before I/R; LR and LA were quantified in single postcapillary venules in the jejunum using intravital microscopy. I/R induced comparable marked increases in LR and LA in WT and eNOS(-/-) mice relative to sham-operated (no ischemia) animals. Late AICAR PC prevented postischemic LR and LA, whereas early AICAR PC prevented LA in WT mice. Late AICAR PC was ineffective in preventing I/R-induced LR but not LA in the eNOS(-/-) mice, and the same pattern was seen in WT animals treated with the NOS inhibitor N(omega)-nitro-l-arginine. Early AICAR PC remained effective in preventing LA in eNOS(-/-) mice. Our results indicate that both early and late PC with an AMPK agonist produces an anti-inflammatory phenotype in postcapillary venules. Since the protection afforded by late AICAR PC on postischemic LR was prevented by NOS inhibition in WT mice and absent in eNOS-deficient mice, it appears that eNOS triggers this protective effect. In stark contrast, antecedent AMPK activation prevented I/R-induced LA by an eNOS-independent mechanism.
Mesh Headings (Keywords): Aminoimidazole Carboxamide, Animals, Cell Adhesion, Endothelial Cells, Enzyme Activation, Ischemic Preconditioning, Myocardial, Leukocytes, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Multienzyme Complexes, Myocardial Reperfusion Injury, Protein-Serine-Threonine Kinases, Ribonucleotides, Treatment Outcome
Check for Full Text / PubMed Unique Identifier (PMID): 16935999
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