Epigenetic upregulation of miR-126 induced by heat stress contributes to apoptosis of rat cardiomyocytes by promoting Tomm40 transcription
TOMM40 is the channel-forming subunit of a translocase of the mitochondrial outer membrane (TOM) that is essential for protein transport into mitochondria. TOMM40 plays an important role in maintaining normal mitochondrial function. The correlation between occupational thermal exposure and mitochond...
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Veröffentlicht in: | Journal of molecular and cellular cardiology 2019-04, Vol.129, p.39-48 |
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Sprache: | eng |
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Zusammenfassung: | TOMM40 is the channel-forming subunit of a translocase of the mitochondrial outer membrane (TOM) that is essential for protein transport into mitochondria. TOMM40 plays an important role in maintaining normal mitochondrial function. The correlation between occupational thermal exposure and mitochondria dysfunction has been demonstrated; however, nothing is known about the alteration and role of TOMM40 in response to environmental heat stress. In the present study, we showed that environmental thermal exposure upregulated microRNA miR-126, consequently reducing AU-rich element RNA-binding protein 1 (AUF1)-mediated SP1 mRNA degradation and increasing TOMM40 transcription, which in turn decreased the mitochondria membrane potential and apoptosis of cardiomyocytes. Mechanistically, miR-126 upregulation was attributed to heat stress-induced promoter demethylation via elevated TET2 (Tet methylcytosine dioxygenase 2) expression, while SP1 mRNA degradation was caused by decreased translation of AUF1 induced by miR-126. Moreover, TOMM40 transcription was upregulated via increasing its transcription factor SP1 resulting from AUF1 inhibition in the heat stress responses. The results of the present study increased our understanding of the role of miR-126 and TOMM40 in heat stressed cardiomyocytes.
•Environmental thermal exposure induced cardiomyocytes apoptosis via TOMM40.•Upregulation of miR-126 contributes to mitochondrial disorder.•TET2 promotes epigenetic upregulation of miR-126 induced by heat stress. |
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ISSN: | 0022-2828 1095-8584 |
DOI: | 10.1016/j.yjmcc.2018.10.005 |