HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/F741    most recent 00313.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in AJP - Renal Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Kim, N.-H. Articles by Gorin, Y. Search for Related Content PubMed PubMed Citation Articles by Kim, N.-H. Articles by Gorin, Y.

Redox dependence of glomerular epithelial cell hypertrophy in response to glucose

¹Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio; ²Department of Medicine, Chonnam National University Hospital, Gwangju, South Korea; and ³Audie L. Murphy Memorial Hospital Division and ⁴Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas

Podocytes or glomerular epithelial cells (GECs) are important targets of the diabetic microenvironment. Podocyte foot process effacement and widening, loss of GECs and hypertrophy are pathological features of this disease. ANG II and oxidative stress are key mediators of renal hypertrophy in diabetes. The cellular mechanisms responsible for GEC hypertrophy in diabetes are incompletely characterized. We investigated the effect of high glucose on protein synthesis and GEC hypertrophy. Exposure of GECs to high glucose dose dependently stimulated [³H]leucine incorporation, but not [³H]yhymidine incorporation. High glucose resulted in the activation of ERK1/2 and Akt/PKB. ERK1/2 pathway inhibitor or the dominant negative mutant of Akt/PKB inhibited high glucose-induced protein synthesis. High glucose elicited a rapid generation of reactive oxygen species (ROS). The stimulatory effect of high glucose on ROS production, ERK1/2, and Akt/PKB activation was prevented by the antioxidants catalase, diphenylene iodonium, and N-acetylcysteine. Exposure of the cells to hydrogen peroxide mimicked the effects of high glucose. In addition, ANG II resulted in the activation of ERK1/2 and Akt/PKB and GEC hypertrophy. Moreover, high glucose and ANG II exhibited additive effects on ERK1/2 and Akt/PKB activation as well as protein synthesis. These additive responses were abolished by treatment of the cells with the antioxidants. These data demonstrate that high glucose stimulates GEC hypertrophy through a ROS-dependent activation of ERK1/2 and Akt/PKB. Enhanced ROS generation accounts for the additive effects of high glucose and ANG II, suggesting that this signaling cascade contributes to GEC injury in diabetes.

high glucose; angiotensin II; podocytes; reactive oxygen species; protein synthesis; hypertrophy

Related articles in AJP - Renal:

Corrigenda

AJP - Renal 2006 291: F254-F255. [Full Text]  

This article has been cited by other articles:

				H.-T. Kuo, H.-W. Chen, H.-H. Hsiao, and H.-C. Chen Heat shock response protects human peritoneal mesothelial cells from dialysate-induced oxidative stress and mitochondrial injury Nephrol. Dial. Transplant., June 1, 2009; 24(6): 1799 - 1809. [Abstract] [Full Text] [PDF]

				A. A. Eid, Y. Gorin, B. M. Fagg, R. Maalouf, J. L. Barnes, K. Block, and H. E. Abboud Mechanisms of Podocyte Injury in Diabetes: Role of Cytochrome P450 and NADPH Oxidases Diabetes, May 1, 2009; 58(5): 1201 - 1211. [Abstract] [Full Text] [PDF]

				P. G. Tipping Are Podocytes Passive or Provocative in Proteinuric Glomerular Pathology? J. Am. Soc. Nephrol., April 1, 2008; 19(4): 651 - 653. [Full Text] [PDF]

				R. V. Durvasula and S. J. Shankland Activation of a local renin angiotensin system in podocytes by glucose Am J Physiol Renal Physiol, April 1, 2008; 294(4): F830 - F839. [Abstract] [Full Text] [PDF]

				S. Graham, M. Ding, S. Sours-Brothers, T. Yorio, J.-X. Ma, and R. Ma Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca2+ signaling in glomerular mesangial cells in diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1381 - F1390. [Abstract] [Full Text] [PDF]

				S.-L. Zhang, Y.-W. Chen, S. Tran, I. Chenier, M.-J. Hebert, and J. R. Ingelfinger Reactive Oxygen Species in the Presence of High Glucose Alter Ureteric Bud Morphogenesis J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2105 - 2115. [Abstract] [Full Text] [PDF]

				J. Chintapalli, S. Yang, D. Opawumi, S. R. Goyal, N. Shamsuddin, A. Malhotra, K. Reiss, and L. G. Meggs Inhibition of wild-type p66ShcA in mesangial cells prevents glycooxidant-dependent FOXO3a regulation and promotes the survival phenotype Am J Physiol Renal Physiol, February 1, 2007; 292(2): F523 - F530. [Abstract] [Full Text] [PDF]

				C. Szabo, A. Biser, R. Benko, E. Bottinger, and K. Susztak Poly(ADP-Ribose) Polymerase Inhibitors Ameliorate Nephropathy of Type 2 Diabetic Leprdb/db Mice Diabetes, November 1, 2006; 55(11): 3004 - 3012. [Abstract] [Full Text] [PDF]