scholarly journals AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

2019 ◽  
Vol 60 (5) ◽  
pp. 937-952 ◽  
Author(s):  
Anne-Emilie Declèves ◽  
Anna V. Mathew ◽  
Aaron M. Armando ◽  
Xianlin Han ◽  
Edward A. Dennis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kidney Disease ◽  
Ampk Activation ◽  
High Fat ◽  
Kinase Activation ◽  
Venous Circulation ◽  
Protein Kinase Activation ◽  
Anti Inflammatory ◽  
Amp Activated Protein Kinase

High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMP-activated protein kinase (AMPK) activation. Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative MS to determine PUFA and eicosanoid content in kidneys, urine, and renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free pro-inflammatory arachidonic acid (AA) and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA- and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPA-derived LOX and NE metabolites decreased. Conversely, treatment with 5-aminoimidazole-4-carboxamide-1-β-D-furanosyl 5′-monophosphate (AICAR), an AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, kidney and circulating AA, AA metabolites, EPA-derived LOX, and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro- and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

scholarly journals Beneficial Role of Erythrocyte Adenosine A2B Receptor–Mediated AMP-Activated Protein Kinase Activation in High-Altitude Hypoxia

Circulation ◽  
2016 ◽  
Vol 134 (5) ◽  
pp. 405-421 ◽  
Author(s):  
Hong Liu ◽  
Yujin Zhang ◽  
Hongyu Wu ◽  
Angelo D’Alessandro ◽  
Gennady G. Yegutkin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
High Altitude ◽  
Altitude Hypoxia ◽  
Kinase Activation ◽  
Beneficial Role ◽  
Protein Kinase Activation ◽  
A2b Receptor ◽  
Amp Activated Protein Kinase ◽  
Adenosine A2b

5′-AMP-activated protein kinase activation prevents postischemic leukocyte-endothelial cell adhesive interactions

2007 ◽  
Vol 292 (1) ◽  
pp. H326-H332 ◽  
Author(s):  
F. Spencer Gaskin ◽  
Kazuhiro Kamada ◽  
Mozow Yusof ◽  
Ronald J. Korthuis
Keyword(s):  
Protein Kinase ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Ampk Activation ◽  
No Donors ◽  
Kinase Activation ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Adhesive Interactions ◽  
Amp Activated Protein Kinase

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-β-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 Nω-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.

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