This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/1/77    most recent 01.ATV.0000251006.54632.bbv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liang, M. Articles by Pietrusz, J. L. Search for Related Content PubMed PubMed Citation Articles by Liang, M. Articles by Pietrusz, J. L.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:77.)
© 2007 American Heart Association, Inc.

Vascular Biology

Thiol-Related Genes in Diabetic Complications

A Novel Protective Role for Endogenous Thioredoxin 2

Mingyu Liang; Jennifer L. Pietrusz

From the Department of Physiology, Medical College of Wisconsin, Milwaukee.

Correspondence to Mingyu Liang, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail mliang{at}mcw.edu

Objective— Our laboratory and others have found that deficiencies in cellular thiols may be importantly involved in the development of diabetic complications. However, the role for specific thiol-related genes in diabetic complications is unclear.

Methods and Results— We began the present study by systematically determining the expression level of 11 thiol-related genes in three tissues from rats with streptozotocin-induced diabetes. Several thiol-related genes were found to exhibit diabetes-associated, time-dependent differential expression. Thioredoxin 2, a mitochondrion-specific thioredoxin whose role in diabetes was unknown, was suppressed in the aorta from rats with two weeks of diabetes. When thioredoxin 2 expression in human umbilical vein endothelial cells was knocked-down by small interfering RNA, high-ambient glucose-elicited substantial injurious effects (n=5 to 9, P<0.05), including increases in cytosolic cytochrome c (by 2.2±0.6-fold), lipid peroxidation (by 40±8%), fibronectin expression (by 35±7%), and oxidized glutathione, and decreases in endothelial nitric oxide synthase expression (by 79±15%), basal accumulation of nitrite/nitrate (by 68±16%), total free thiols (by 42±8%), and glutathione (by 6±1%). In the absence of thioredoxin 2 knockdown, high-ambient glucose did not have significant effects on any of these measurements. The effect of thioredoxin 2 knockdown appeared to be associated with increases in glucose consumption and glucose transporter 1 expression.

Conclusion— These results provided the first expression profile of thiol-related genes in a model of diabetes and demonstrated a novel role for endogenous thioredoxin 2 in protecting cells against high ambient glucose.

There is emerging evidence that cellular thiols may be importantly involved in diabetic complications. We systematically determined the expression level of 11 thiol-related genes in streptozotocin-induced diabetes. Thioredoxin 2, a mitochondrion thioredoxin suppressed in the aorta by diabetes, was found to protect human endothelial cells from high ambient glucose.

Key Words: type 1 diabetes • functional genomics • vascular biology • nitric oxide • oxidative stress

This article has been cited by other articles:

				M. Liang, N. H. Lee, H. Wang, A. S. Greene, A. E. Kwitek, M. L. Kaldunski, T. V. Luu, B. C. Frank, S. Bugenhagen, H. J. Jacob, et al. Molecular networks in Dahl salt-sensitive hypertension based on transcriptome analysis of a panel of consomic rats Physiol Genomics, June 10, 2008; 34(1): 54 - 64. [Abstract] [Full Text] [PDF]

				Z. Tian, A. S. Greene, K. Usa, I. R. Matus, J. Bauwens, J. L. Pietrusz, A. W. Cowley Jr, and M. Liang Renal Regional Proteomes in Young Dahl Salt-Sensitive Rats Hypertension, April 1, 2008; 51(4): 899 - 904. [Abstract] [Full Text] [PDF]

				Z. Tian, A. S. Greene, J. L. Pietrusz, I. R. Matus, and M. Liang MicroRNA-target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis Genome Res., March 1, 2008; 18(3): 404 - 411. [Abstract] [Full Text] [PDF]

				Y. Liu, F. Park, J. L. Pietrusz, G. Jia, R. J. Singh, B. C. Netzel, and M. Liang Suppression of 11{beta}-hydroxysteroid dehydrogenase type 1 with RNA interference substantially attenuates 3T3-L1 adipogenesis Physiol Genomics, February 19, 2008; 32(3): 343 - 351. [Abstract] [Full Text] [PDF]

				K. Usa, R. J. Singh, B. C. Netzel, Y. Liu, H. Raff, and M. Liang Renal interstitial corticosterone and 11-dehydrocorticosterone in conscious rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F186 - F192. [Abstract] [Full Text] [PDF]

				P. Patwari and R. T. Lee Thioredoxins, Mitochondria, and Hypertension Am. J. Pathol., March 1, 2007; 170(3): 805 - 808. [Abstract] [Full Text] [PDF]