Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration.
Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.
Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200, Chile.
Daniela K
DK
Montes
Marianne
M
Brenet
Vanessa C
VC
Muñoz
Patricia V
PV
Burgos
Carolina I
CI
Villanueva
Carlos D
CD
Figueroa
Carlos B
CB
González
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000201:enzymology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D009025:Morpholines / Q000494:pharmacology; D046912:Multiprotein Complexes / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; D046912:Multiprotein Complexes; D001127:Arginine Vasopressin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
AMP-activated protein kinase; AMPK; AVP; Akt; ERK; PI3-kinase; PI3K; PKC; PLD; Rheb; TSC1/TSC2; Vascular remodeling; Vasopressin; arginine vasopressin; extracellular regulated-kinase; mTOR; mTOR complex 1; mTORC1; mammalian target of rapamycin; phosphatidyl inositol-3 kinase; phospholipase D; protein kinase C, Akt or protein kinase B; ras homolog enriched in brain; tubero sclerosis protein 1 and 2