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Alterations in mitochondrial function and cytosolic calcium transients induced by hyperglycemia are restored by over‐expression of mitochondrial transcription factor A (TFAM) in cardiomyocytes
Author(s) -
Suarez Jorge,
Hu Yong,
Makino Ayako,
Fricovsky Eduardo,
Dillmann Wolfgang H.
Publication year - 2008
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.22.1_supplement.1226.23
Subject(s) - tfam , mitochondrial dna , mitochondrion , biology , calcium , medicine , endocrinology , microbiology and biotechnology , chemistry , biochemistry , gene , mitochondrial biogenesis
TFAM is essential for mitochondrial DNA transcription and replication. TFAM expression is decreased in diabetic cardiomyopathy; however, the functional implications are unknown. We hypothesized that a reduced TFAM activity may be responsible for some of the alterations caused by hyperglycemia. Therefore, we investigated the effect of TFAM over‐expression on hyperglycemia‐induced cytosolic calcium handling and mitochondrial abnormalities. Neonatal rat cardiomyocytes were exposed to high glucose (30mM) for 48 h and examined whether TFAM over‐expression, by protecting mtDNA, could reestablish calcium fluxes and mitochondrial alterations towards normal. Our results show that TFAM over‐expression increased two fold mitochondrial DNA copy number in cells treated with high glucose. High glucose induced a reduction in ATP content and mitochondrial [Ca 2+ ] (30% and 40% respectively) and TFAM over‐expression returned these parameters to control values. Calcium transients were prolonged by 70 % after high glucose treatment which was associated with diminished SERCA2a expression. These parameters were improved by TFAM over‐expression. In addition, we found that TFAM activity can be modulated by O‐linked β‐N‐acetylglucosamine glycosylation. In conclusion, TFAM over‐expression protected cell function against the damage induced by hyperglycemia in cardiomyocytes.