Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase.
The present study examined whether adiponectin can inhibit palmitate-induced apoptosis, and also the associated mechanisms and signal transduction pathways in human umbilical vein endothelial cells. Cells treated with 500 μM palmitate for 48 h increased reactive oxygen species (ROS) generation and induced apoptosis. Treatment with antioxidant N-acetyl-L-cysteine (1 mM) and globular adiponectin (5 μg/ml) inhibited palmitate-induced ROS generation and apoptosis. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 1 mM), and cAMP activators forskolin (10 μM) and cholera toxin (200 ng/ml) also displayed the same effects. The inhibitory effects of adiponectin on ROS generation and apoptosis were reversed by the AMPK inhibitor compound C (40 μM), cAMP inhibitor SQ22536 (50 μM), and protein kinase A (PKA) inhibitor H-89 (10 μM). The inhibitory effect of forskolin on palmitate-induced apoptosis was reversed by compound C, whereas the inhibitory effect of AICAR was not reversed by SQ22536 and H-89. AICAR and forskolin could not inhibit palmitate-induced apoptosis in cells treated with dominant-negative AMPK. Forskolin increased phosphorylated AMPK at both Thr-172 and Ser-485/491. These results suggest that adiponectin inhibits palmitate-induced apoptosis by suppression of ROS generation via both the cAMP/PKA and AMPK pathways. Interaction between cAMP/PKA and AMPK pathways may be involved.
Kim
Ji-Eun
JE
Department of Physiology, College of Medicine, Yeungnam University, Daegu, South Korea.
Song
Seung Eun
SE
Kim
Yong-Woon
YW
Kim
Jong-Yeon
JY
Park
Sung-Chul
SC
Park
Yoon-Ki
YK
Baek
Suk-Hwan
SH
Lee
In Kyu
IK
Park
So-Young
SY
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019308:Palmitic Acid / Q000494:pharmacology*; D010714:Phosphatidylethanolamines; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C499918:ADIPOQ protein, human; D052242:Adiponectin; D010714:Phosphatidylethanolamines; D017382:Reactive Oxygen Species; C100004:transfectACE; D019308:Palmitic Acid; D000242:Cyclic AMP; C526181:PRKAA2 protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human