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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Biochem+Cell+Biol
2014 ; 54
(ä): 1-9
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AMPK is involved in mediation of erythropoietin influence on metabolic activity
and reactive oxygen species production in white adipocytes
#MMPMID24953559
Wang L
; Di L
; Noguchi CT
Int J Biochem Cell Biol
2014[Sep]; 54
(ä): 1-9
PMID24953559
show ga
Erythropoietin, discovered for its indispensable role during erythropoiesis, has
been used in therapy for selected red blood cell disorders in
erythropoietin-deficient patients. The biological activities of erythropoietin
have been found in animal models to extend to non-erythroid tissues due to the
expression of erythropoietin receptor. We previously demonstrated that
erythropoietin promotes metabolic activity and white adipocytes browning to
increase mitochondrial function and energy expenditure via peroxisome
proliferator-activated receptor alpha and Sirtuin1. Here we report that
AMP-activated protein kinase was activated by erythropoietin possibly via
Ca(2+)/calmodulin-dependent protein kinase kinase in adipocytes as well as in
white adipose tissue from diet induced obese mice. Erythropoietin increased
cellular nicotinamide adenine dinucleotide via increased AMP-activated protein
kinase activity, possibly leading to Sirtuin1 activation. AMP-activated protein
kinase knock down reduced erythropoietin mediated increase in cellular oxidative
function including the increased oxygen consumption rate, fatty acid utilization
and induction of key metabolic genes. Under hypoxia, adipocytes were found to
generate more reactive oxygen species, and erythropoietin reduced the reactive
oxygen species and increased antioxidant gene expression, suggesting that
erythropoietin may provide protection from oxidative stress in adipocytes.
Erythropoietin also reversed increased nicotinamide adenine dinucleotide by
hypoxia via increased AMP-activated protein kinase. Additionally, AMP-activated
protein kinase is found to be involved in erythropoietin stimulated increase in
oxygen consumption rate, fatty acid oxidation and mitochondrial gene expression.
AMP-activated protein kinase knock down impaired erythropoietin stimulated
increases in antioxidant gene expression. Collectively, our findings identify the
AMP-activated protein kinase involvement in erythropoietin signaling in
regulating adipocyte cellular redox status and metabolic activity.
|AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/*metabolism
[MESH]