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miRNA‐141 is a potential regulator of the mitochondrial phosphate carrier (slc25a3) in the type 1 diabetic heart
Author(s) -
Thapa Dharendra,
Baseler Walter A,
Jagannathan Rajaganapathi,
Dabkowski Erinne R,
Croston Tara L,
Nichols Cody E,
Shepherd Danielle L,
Lewis Sara E,
Hollander John M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.869.11
Subject(s) - regulator , diabetic cardiomyopathy , microrna , diabetes mellitus , hek 293 cells , mitochondrion , solute carrier family , medicine , endocrinology , microbiology and biotechnology , streptozotocin , biology , pharmacology , cardiomyopathy , heart failure , transporter , biochemistry , gene , receptor
Cardiomyopathy is a leading cause of mortality among patients with diabetes mellitus. Dysfunctional mitochondria are central in the pathogenesis of diabetic cardiomyopathy. Mitochondrial proteomic alterations during diabetes mellitus have been reported however, the mechanisms responsible are unknown. The goal of this study was to determine whether miRNAs, specifically miRNA‐141, play a role in diabetes‐induced proteomic dysregulation. miRNA screening in diabetic mice following multiple low‐dose streptozotocin treatment revealed a significant increase in the expression of 10 miRNAs in the heart, including miRNA‐141 (P<0.05). Target scan analyses identified miRNA‐141 as a potential regulator of the inner membrane phosphate transporter, solute carrier family 25 member 3 (slc25a3), which provides inorganic phosphate essential for ATP production. miRNA‐141 overexpression in HEK 293 cells elicited a decrease in slc25a3 protein content similar to the diabetic phenotype (P<0.05). Moreover, ATP synthase activity was decreased in miRNA‐141 overexpressed HEK 293 cells similar to diabetes mellitus. Together these results indicate that miRNA‐141 could be a potential regulator of slc25a3 protein expression in the diabetic heart. Further, diabetes‐induced miRNA changes may influence mitochondrial proteomes and functional processes.(Support: NIH DP2DK083095, NIH T32HL090610, AHA 10PRE3420006)