| miR-141 as a regulator of the mitochondrial phosphate carrier (Slc25a3) in the type 1 diabetic heart. | |
| | |
MedLine Citation:
|
PMID: 23034391 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Dysfunctional mitochondria are central in the pathogenesis of diabetic cardiomyopathy. Mitochondrial proteomic alterations resulting from diabetes mellitus have been reported although the mechanisms driving changes in proteomic signatures are unknown. microRNAs (miRNAs) have been considered as potential regulators of proteins. The goal of this study was to determine whether miRNAs play a role in diabetes-induced mitochondrial proteomic alterations. Quanitative RT-PCR miRNA screening in diabetic mice, 5 wk following multiple low-dose streptozotocin treatment was associated with alteration in the expression of 29 miRNAs in the diabetic heart compared with control. Among those miRNAs upregulated in the diabetic heart was miR-141 (P < 0.002). miRNA target prediction analyses identified miR-141 as a potential regulator of the inner mitochondrial membrane phosphate transporter, solute carrier family 25 member 3 (Slc25a3), which provides inorganic phosphate to the mitochondrial matrix and is essential for ATP production. With the use of a luciferase reporter construct with a Slc25a3 3'-untranslated region (UTR) target sequence, overexpression of miR-141 downregulated luciferase activity levels confirming miR-141/Slc25a3 3'-UTR binding. miR-141 overexpression in HL-1 cells elicited a decrease in Slc25a3 protein content, ATP production and a decrease in ATP synthase activity, similar to the diabetic phenotype (P < 0.05, for both). Diabetic interfibrillar mitochondria (IFM) displayed decreased Slc25a3 protein content, which was inversely correlated with increased miR-141 expression. Further, diabetic IFM ATP synthase activity was also decreased (P < 0.05). Together these results indicate that miR-141 can regulate Slc25a3 protein expression in the diabetic heart. Further, diabetes-induced miRNA changes may influence mitochondrial proteomes and functional processes such as mitochondrial ATP production. |
| | |
Authors:
|
Walter A Baseler; Dharendra Thapa; Rajaganapathi Jagannathan; Erinne R Dabkowski; Tara L Croston; John M Hollander |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-03 |
Journal Detail:
|
Title: American journal of physiology. Cell physiology Volume: 303 ISSN: 1522-1563 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-17 Completed Date: 2013-02-26 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: C1244-51 Citation Subset: IM |
Affiliation:
|
Center for Cardiovascular and Respiratory Sciences, Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV 26506, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Diabetes Mellitus, Experimental / metabolism* Diabetes Mellitus, Type 1 / metabolism* Diabetic Cardiomyopathies / metabolism* Male Mice MicroRNAs / metabolism* Mitochondria, Heart / metabolism Mitochondrial Proteins / biosynthesis* Mitochondrial Proton-Translocating ATPases / metabolism Phosphate Transport Proteins / biosynthesis* |
| Grant Support | |
ID/Acronym/Agency:
|
DP2-DK-083095/DK/NIDDK NIH HHS; T32HL090610/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/MicroRNAs; 0/Mirn141 microRNA, mouse; 0/Mitochondrial Proteins; 0/Phosphate Transport Proteins; 0/SLC25A3 protein, human; EC 3.6.3.-/Mitochondrial Proton-Translocating ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary h...
Next Document: Compensable occupational disease and cancer: how to improve the recognition rate? "Cursus Laboris" P...