Diabetes 2013 Aug-9

 

Metallothionein prevents diabetes-induced cardiac pathological changes, likely via the inhibition of succinyl-CoA:3-ketoacid coenzyme A transferase-1 nitration at Trp(374).

Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E826-35.

Cong W, Ma W, Zhao T, Zhu Z, Wang Y, Tan Y, Li X, Jin L, Cai L.

Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Zhejiang, China.

 

Abstract: 

We have demonstrated that metallothionein (MT) prevention of diabetic cardiomyopathy is related to its suppression of superoxide generation and associated protein nitration. However, which one among diabetes-nitrated proteins plays the critical role in the development of diabetic cardiomyopathy remains unknown. The present study was to identify the distinguishable proteins that were nitrated in the heart of wild-type (WT) diabetes, but not cardiac-specific MT-overexpressing transgenic (MT-TG) mice. MT-TG and WT mice were induced to diabetic with a streptozotocin. Hearts were collected at 2, 4, 8, and 16 weeks after diabetes. Histopathological examination confirmed the development of diabetic cardiomyopathy in WT, but not MT-TG, mice, reflected by derangement of the cardiac structure and remodeling as well as the significant increase of superoxide generation and 3-nitrotyrosine accumulation.

We have found that the predominant proteins that were nitrated in the WT diabetic heart, but not in MT-TG diabetic heart are the proteins that should include mitochondrial proteins. This suggests that one of these mitochondrial proteins that are susceptible to be nitrated under diabetic conditions may play the critical role in the prevention of diabetic cardiomyopathy since to avoid its nitration in the MT-TG diabetic heart could result in a prevention of diabetic cardiomyopathy.

The present study, therefore, was to investigate the distinguishable nitrated proteins between WT and MT-TG diabetic hearts since these proteins, once nitrated, may play the critical role in the development of diabetic cardiomyopathy. Eighty-nine nitrated proteins that are predominantly involved in mitochondrial energy metabolism were identified in the hearts of WT diabetic mice. One of these nitrated proteins is SCOT that was nitrated in WT, but not MT-TG diabetic hearts. Further analysis indicated that diabetes does not significantly affect SCOT protein expression, but significantly increases its nitration that leads to remarkable reduction of SCOT enzyme activity in the heart of WT diabetic mice. Mass spectra (MS) analysis revealed that the nitration level of SCOT Tyr76 and Trp374 sites were significantly higher in the WT diabetic heart, but only Trp374 nitration was significant attenuated by MT. We assumed that MT protects the heart from diabetes most likely via its prevention of SCOT Trp374 nitration to preserve its enzyme activity for mitochondrial energy metabolism.

 

Keywords: Diabetic cardiomyopathy; metallothionein; SCOT; 3-nitrotyrosine

Link:http://www.ncbi.nlm.nih.gov/pubmed/23423173

 

Supplementary picuture:

Li-Tai Jin-1

 

Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann