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SHR Neuro Cancer Cardio Lipid Metab Microb

Pandey, S; Madreiter-Sokolowski, CT; Mangmool, S; Parichatikanond, W.
High Glucose-Induced Cardiomyocyte Damage Involves Interplay between Endothelin ET-1/ETA/ETB Receptor and mTOR Pathway
INT J MOL SCI. 2022; 23(22): 13816 Doi: 10.3390/ijms232213816 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Leading authors Med Uni Graz

Parichatikanond Warisara

Co-authors Med Uni Graz

Madreiter-Sokolowski Corina

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Abstract:

Patients with type two diabetes mellitus (T2DM) are at increased risk for cardiovascular diseases. Impairments of endothelin-1 (ET-1) signaling and mTOR pathway have been implicated in diabetic cardiomyopathies. However, the molecular interplay between the ET-1 and mTOR pathway under high glucose (HG) conditions in H9c2 cardiomyoblasts has not been investigated. We employed MTT assay, qPCR, western blotting, fluorescence assays, and confocal microscopy to assess the oxidative stress and mitochondrial damage under hyperglycemic conditions in H9c2 cells. Our results showed that HG-induced cellular stress leads to a significant decline in cell survival and an impairment in the activation of ETA-R/ETB-R and the mTOR main components, Raptor and Rictor. These changes induced by HG were accompanied by a reactive oxygen species (ROS) level increase and mitochondrial membrane potential (MMP) loss. In addition, the fragmentation of mitochondria and a decrease in mitochondrial size were observed. However, the inhibition of either ETA-R alone by ambrisentan or ETA-R/ETB-R by bosentan or the partial blockage of the mTOR function by silencing Raptor or Rictor counteracted those adverse effects on the cellular function. Altogether, our findings prove that ET-1 signaling under HG conditions leads to a significant mitochondrial dysfunction involving contributions from the mTOR pathway.

Find related publications in this database (Keywords)

high glucose

endothelin-1

ETA-R

ETB-R

mTOR

mitochondrial dysfunction

oxidative stress

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