Nicorandil attenuates endothelial VCAM‑1 expression via thioredoxin production in diabetic rats induced by streptozotocin

Liu,Lihua; Liu,Yun; Qi,Benling; Wu,Qinqin; Li,Yuanyuan; Wang,Zhaohui

doi:10.3892/mmr.2014.2066

June-2014 Volume 9 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

June-2014 Volume 9 Issue 6

Full Size Image

Article

Nicorandil attenuates endothelial VCAM‑1 expression via thioredoxin production in diabetic rats induced by streptozotocin

Authors:
- Lihua Liu
- Yun Liu
- Benling Qi
- Qinqin Wu
- Yuanyuan Li
- Zhaohui Wang
View Affiliations / Copyright

Affiliations: Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China, Department of Geriatrics, The Central Hospital of Wuhan, Wuhan 430014, P.R. China, Department of Geriatrics, Wuhan General Hospital of Guangzhou Military, Wuhan 430070, P.R. China
Pages: 2227-2232
|
Published online on: March 24, 2014

https://doi.org/10.3892/mmr.2014.2066
Expand metrics +

Abstract

The anti‑angina agent nicorandil has been reported to be beneficial even in patients who have angina with diabetes. However, the mechanism underlying the effect of nicorandil in patients with diabetes remains to be elucidated. In this study, the protective effect of nicorandil on thioredoxin (TRX) protein was investigated, as TRX is a multifunctional endogenous redox regulator that protects cells against various types of cellular and tissue stress. This study was conducted to examine whether nicorandil induces the expression of TRX for the protection against diabetic damage in the vascular tissue of rats. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (STZ) (fasting glucose levels in STZ‑induced rats were >14 mmol/l). Diabetic rats were divided into a diabetic control and a nicorandil‑treated group. Nicorandil was administered at a dosage of 15 mg/kg/day by gavage feeding. After five weeks of nicorandil administration, blood samples were obtained from the angular vein to measure levels of stress markers, serum superoxide dismutase and malondialdehyde, using the ELISA. The expression of TRX in STZ‑induced rat vascular tissue was analyzed by immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blot analysis. The oral administration of nicorandil induced TRX protein and mRNA expression in the vascular tissue of STZ‑induced diabetic rats. In the diabetic control group, the levels of stress were markedly higher than those in the nicorandil‑treated group, indicating that nicorandil reduces oxidative stress in serum. In addition to inducing TRX expression, nicorandil attenuated the expression of the vascular cell adhesion molecule‑1 (VCAM‑1) in diabetic rat vascular endothelial cells. In conclusion, nicorandil attenuates the formation of reactive oxygen species and induces TRX protein expression, consequently resulting in the suppression of VCAM‑1 secretion in the vascular endothelial cells of STZ‑induced diabetic rats.

View Figures

View References

1	Cai L and Kang YJ: Oxidative stress and diabetic cardiomyopathy: a brief review. Cardiovasc Toxicol. 1:181–193. 2001. View Article : Google Scholar : PubMed/NCBI
2	Schaffer SW, Jong CJ and Mozaffari M: Role of oxidative stress in diabetes-mediated vascular dysfunction: Unifying hypothesis of diabetes revisited. Vascul Pharmacol. 57:139–149. 2012. View Article : Google Scholar : PubMed/NCBI
3	Schulze PC, Yoshioka J, Takahashi T, He Z, King GL and Lee RT: Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem. 279:30369–30374. 2004. View Article : Google Scholar : PubMed/NCBI
4	Mahmood DF, Abderrazak A, El Hadri K, Simmet T and Rouis M: The thioredoxin system as a therapeutic target in human health and disease. Antioxid Redox Signal. 19:1266–1303. 2013. View Article : Google Scholar : PubMed/NCBI
5	Hwang J, Suh HW, Jeon YH, et al: The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein. Nat Commun. 5:29582014. View Article : Google Scholar : PubMed/NCBI
6	Dunn LL, Buckle AM, Cooke JP and Ng MK: The emerging role of the thioredoxin system in angiogenesis. Arterioscler Thromb Vasc Biol. 30:2089–2098. 2010. View Article : Google Scholar : PubMed/NCBI
7	Yamawaki H, Pan S, Lee RT and Berk BC: Fluid shear stress inhibits vascular inflammation by decreasing thioredoxin-interacting protein in endothelial cells. J Clin Invest. 115:733–738. 2005. View Article : Google Scholar : PubMed/NCBI
8	IONA study group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet. 359:1269–1275. 2002. View Article : Google Scholar : PubMed/NCBI
9	Horinaka S, Yabe A, Yagi H, et al: Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese Coronary Artery Disease (JCAD) study. Circ J. 74:503–509. 2010. View Article : Google Scholar : PubMed/NCBI
10	Walker A, McMurray J, Stewart S, et al: Economic evaluation of the impact of nicorandil in angina (IONA) trial. Heart. 92:619–624. 2006. View Article : Google Scholar : PubMed/NCBI
11	Taira N: Nicorandil as a hybrid between nitrates and potassium channel activators. Am J Cardiol. 63:18J–24J. 1989. View Article : Google Scholar : PubMed/NCBI
12	Reimann F, Ashcroft FM and Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 50:2253–2259. 2001. View Article : Google Scholar : PubMed/NCBI
13	Kasono K, Yasu T, Kakehashi A, et al: Nicorandil improves diabetes and rat islet beta-cell damage induced by streptozotocin in vivo and in vitro. Eur J Endocrinol. 151:277–285. 2004. View Article : Google Scholar : PubMed/NCBI
14	Serizawa K, Yogo K, Aizawa K, Tashiro Y and Ishizuka N: Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats. Cardiovasc Diabetol. 10:1052011. View Article : Google Scholar : PubMed/NCBI
15	Mano T, Shinohara R, Nagasaka A, et al: Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats. Metabolism. 49:427–431. 2000. View Article : Google Scholar : PubMed/NCBI
16	Khan ZA and Chakrabarti S: Cellular signaling and potential new treatment targets in diabetic retinopathy. Exp Diabetes Res. 2007:318672007.PubMed/NCBI
17	Adamiec-Mroczek J and Oficjalska-Młyńczak J: Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes - role of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 246:1665–1670. 2008. View Article : Google Scholar
18	Gustavsson C, Agardh CD, Zetterqvist AV, Nilsson J, Agardh E and Gomez MF: Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia. PLoS One. 5:e126992010. View Article : Google Scholar : PubMed/NCBI
19	Limb GA, Hickman-Casey J, Hollifield RD and Chignell AH: Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 40:2453–2457. 1999.PubMed/NCBI
20	Chao HH, Hong HJ, Sung LC, Chen JJ, Cheng TH and Liu JC: Nicorandil attenuates cyclic strain-induced endothelin-1 expression via the induction of activating transcription factor 3 in human umbilical vein endothelial cells. Eur J Pharmacol. 667:292–297. 2011. View Article : Google Scholar
21	Chae HZ, Chung SJ and Rhee SG: Thioredoxin-dependent peroxide reductase from yeast. J Biol Chem. 269:27670–27678. 1994.PubMed/NCBI
22	World CJ, Yamawaki H and Berk BC: Thioredoxin in the cardiovascular system. J Mol Med (Berl). 84:997–1003. 2006. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Nicorandil attenuates endothelial VCAM‑1 expression via thioredoxin production in diabetic rats induced by streptozotocin

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles