Propionyl-L-carnitine induces eNOS activation and nitric oxide synthesis in endothelial cells via PI3 and Akt kinases.

Propionyl-l-carnitine (PLC) is a natural short-chain derivative of l-carnitine (LC), a natural amino acid that plays an important role in fatty acid metabolism. Recent studies suggest that PLC has vascular protective effects. Because of the importance of endothelial nitric oxide synthase (eNOS) and its product, antiatherogenic molecule nitric oxide (NO), in vascular endothelial function, we sought to elucidate that if PLC would stimulate eNOS and its upstream activators Akt and phosphatidylinositol 3-kinase (PI3 Kinase) in cultured human aortic endothelial cells (HAEC). PLC caused eNOS phosphorylation at Ser-1177, and dominant negative Akt and a novel Akt-selective inhibitor MK-2206 inhibited both PLC-mediated phosphorylation and activation of the enzyme. PI3 kinase inhibition also blocked the phosphorylation and activation of eNOS by PLC. Studies with specific drug inhibitors PD173955 and PP2 showed that the non-receptor tyrosine kinase, src, is an upstream stimulator of the PI3 kinase-Akt pathway in this pathway. In addition, PLC significantly decreased intracellular ATP/ADP ratio and activate AMPK, subsequently leading to Src activation. Finally, we demonstrated that the effects of PLC to augment eNOS activity were associated with a net increase in NO release from endothelial cells. NO production following incubation with PLC was abolished in endothelial cells coincubated with L-NAME, PD173955, LY294002, MK-2206 and compound C. In conclusion, PLC, via AMPK/Src-mediated signaling that leads to activation of PI3 kinase and Akt, stimulates eNOS, leading to increased production of NO.

Ning WH ，Zhao K 《-》

Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells.

Andreozzi F ，Laratta E ，Procopio C ，Hribal ML ，Sciacqua A ，Perticone M ，Miele C ，Perticone F ，Sesti G ... -  《-》

Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway.

Yu J ，Akishita M ，Eto M ，Ogawa S ，Son BK ，Kato S ，Ouchi Y ，Okabe T ... -  《-》

Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells.

Andreozzi F ，Laratta E ，Sciacqua A ，Perticone F ，Sesti G ... -  《-》

AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of the nitric oxide synthase in human platelets.

Fleming I ，Schulz C ，Fichtlscherer B ，Kemp BE ，Fisslthaler B ，Busse R ... -  《THROMBOSIS AND HAEMOSTASIS》