Losartan Affects Glomerular AKT and mTOR Phosphorylation in an Experimental Model of Type 1 Diabetic Nephropathy

被引:25
作者
Mavroeidi, Vasiliki [1 ]
Petrakis, Ioannis [1 ]
Stylianou, Kostas [1 ]
Katsarou, Theodora [1 ]
Giannakakis, Konstantinos [4 ]
Perakis, Kostas [1 ]
Vardaki, Eleftheria [1 ]
Stratigis, Spyridon [1 ]
Ganotakis, Emmanuel [2 ]
Papavasiliou, Stathis [3 ]
Daphnis, Eugenios [1 ]
机构
[1] Univ Crete, Dept Nephrol, Khania, Greece
[2] Univ Crete, Dept Internal Med, Khania, Greece
[3] Univ Crete, Dept Endocrinol, Khania, Greece
[4] Univ Roma La Sapienza, Dept Radiol Oncol & Pathol, Rome, Italy
关键词
losartan; mTOR; AKT; diabetic nephropathy; podocytes; type; 1; diabetes; RENIN-ANGIOTENSIN SYSTEM; MAMMALIAN TARGET; RAPAMYCIN; PATHWAY; DISEASE; CELLS; RATS; PODOCYTES; BLOCKADE; NEPHRIN;
D O I
10.1369/0022155413482925
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.
引用
收藏
页码:433 / 443
页数:11
相关论文
共 27 条
[1]  
Boner G, 1996, DIABETOLOGIA, V39, P587
[2]   The intrarenal renin-angiotensin system and diabetic nephropathy [J].
Carey, RM ;
Siragy, HM .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2003, 14 (06) :274-281
[3]   Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3β/mTOR signaling pathway [J].
Diniz, Gabriela Placona ;
Carneiro-Ramos, Marcela Sorelli ;
Morais Barreto-Chaves, Maria Luiza .
BASIC RESEARCH IN CARDIOLOGY, 2009, 104 (06) :653-667
[4]   Molecular mechanisms of angiotensin II in modulating cardiac function: Intracardiac effects and signal transduction pathways [J].
Dostal, DE ;
Hunt, RA ;
Kule, CE ;
Bhat, GJ ;
Karoor, V ;
McWhinney, CD ;
Baker, KM .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (11) :2893-2902
[5]   The epidemic of type 1 diabetes: what is it telling us? [J].
Forlenza, Gregory P. ;
Rewers, Marian .
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY, 2011, 18 (04) :248-251
[6]   Role of mTOR in podocyte function and diabetic nephropathy in humans and mice [J].
Goedel, Markus ;
Hartleben, Bjoern ;
Herbach, Nadja ;
Liu, Shuya ;
Zschiedrich, Stefan ;
Lu, Shun ;
Debreczeni-Mor, Andrea ;
Lindenmeyer, Maja T. ;
Rastaldi, Maria-Pia ;
Hartleben, Goetz ;
Wiech, Thorsten ;
Fornoni, Alessia ;
Nelson, Robert G. ;
Kretzler, Matthias ;
Wanke, Ruediger ;
Pavenstaedt, Hermann ;
Kerjaschki, Dontscho ;
Cohen, Clemens D. ;
Hall, Michael N. ;
Rueegg, Markus A. ;
Inoki, Ken ;
Walz, Gerd ;
Huber, Tobias B. .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (06) :2197-2209
[7]   ANG II activates effectors of mTOR via PI3-K signaling in human coronary smooth muscle cells [J].
Hafizi, S ;
Wang, XM ;
Chester, AH ;
Yacoub, MH ;
Proud, CG .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (03) :H1232-H1238
[8]   Akt signalling in health and disease [J].
Hers, Ingeborg ;
Vincent, Emma E. ;
Tavare, Jeremy M. .
CELLULAR SIGNALLING, 2011, 23 (10) :1515-1527
[9]   Remission of nephrotic-range albuminuria in type 1 diabetic patients [J].
Hovind, P ;
Rossing, P ;
Tarnow, L ;
Toft, H ;
Parving, J ;
Parving, HH .
DIABETES CARE, 2001, 24 (11) :1972-1977
[10]   A complex interplay between Akt, TSC2 and the two mTOR complexes [J].
Huang, Jingxiang ;
Manning, Brendan D. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2009, 37 :217-222