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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #179025
Title: CARDIAC METALLOTHIONEIN SYNTHESIS IN STREPTOZOTOCIN -INDUCED DIABETIC MICE, AND ITS PROTECTION AGAINST DIABETES-INDUCED CARDIAC INJURY

Author
item SONG, YE - UNIV OF LOUISVILLE, KY
item WANG, JIANXUN - UNIV OF LOUISVILLE, KY
item LI, YAN - UNIV OF LOUISVILLE, KY
item DU, YIBO - UNIV OF LOUISVILLE, KY
item ARTEEL, GAVIN - UNIV OF LOUISVILLE, KY
item Saari, Jack
item KANG, Y - UNIV OF LOUISVILLE, KY
item CAI, LU - UNIV OF LOUISVILLE, KY

Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2005
Publication Date: 7/1/2005
Citation: Song, Y., Wang, J., Li, Y., Du, Y., Arteel, G.E., Saari, J.T., Kang, Y.J., Cai, L. 2005. Cardiac metallothionein synthesis in streptozotocin-induced diabetic mice, and its protection against diabetes-induced cardiac injury. American Journal of Pathology. 167(1):17-26.

Interpretive Summary: Diabetes can produce oxidant stress and inflammation that may impair heart function. Often, such effects can induce compensatory or protective mechanisms that may impede the development of the pathology. Metallothionein (MT) is a protein that is activated in organs undergoing such stresses and can protect the organ against them. The objective of this study was to determine whether MT concentration is altered in hearts of diabetic animals and, if so, what mechanisms may explain the alteration. We found that MT concentration was increased in hearts of diabetic rats. This increase was not correlated with a change in oxidative stress or with heart minerals, which can sometimes induce MT, but was related to the production of molecules associated with inflammation. We conclude that inflammatory events may trigger the increase in MT. This information may be useful in developing strategies to prevent heart complications of diabetes.

Technical Abstract: Objective: Diabetes and its complications are associated with oxidative stress derived from hyperglycemia, hyperlipidemia and inflammation. Metallothionein (MT) as both an antioxidant and a stress-response protein was signficantly increased in the liver and kidneys of diabetic animals. It is unknown whether cardiac MT synthesis is also increased in response to diabetes and what mechanisms are involved in this increase. The purpose of the present study was to investigate cardiac MT expression in diabetic mice. Methods: A mouse model of type 1 diabetes mellitus was induced by single intravenous injection of streptozotocin (STZ) at 150 mg/kg body weight using FVB mice. Cardiac MT expression was examined in the diabetic mice by immunohistochemical staining, Western blotting and cadmium-hemoglobin assays. Results: A significant increase in cardiac MT content was observed in the mice at two weeks and two months after STZ treatment without significant change of cardiac metals, including zinc, copper and iron. The cardiac MT induction was also unrelated to cardiac oxidative damage (lipid peroxidation, as measured by thiobarbituric acid-reactive substance). In these diabetic mice, however, serum vasopeptide endothelin and serum and cardiac inflammatory factor tumor-necrosis factor-alpha were significantly increased. Conclusion: This study suggests that diabetes-induced MT in the hearts is not related to cardiac metals or oxidative damage, but is likely associated with systemic increases in endothelin and tumor-necrosis factor-alpha.