Inhibition of ERK 1/2 pathway downregulates YAP1/TAZ signaling in human cardiomyocytes exposed to hyperglycemic conditions

Joddar, Binata; Loyola, Carla D.; Ramirez, Salma P.; Singh, Irtisha

doi:10.1016/j.bbrc.2023.01.014

Biochemical and Biophysical Research Communications

2023

DOI: 10.1016/j.bbrc.2023.01.014

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Inhibition of ERK 1/2 pathway downregulates YAP1/TAZ signaling in human cardiomyocytes exposed to hyperglycemic conditions

Binata Joddar

Carla D. Loyola

Salma P. Ramirez

et al.

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2024

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Cited by 1 publication

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Of cells and tissues: Identifying the elements of a diabetic cardiac in vitro study model

Hernandez,

Gobinath,

Padilla

et al. 2024

Preprint

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This study aimed to elucidate the impact of advanced glycation end products (AGEs) and glucose shock on cardiomyocyte viability, gene expression, cardiac biomarkers, and cardiac contractility. Firstly, AGEs were generated in-house, and their concentration was confirmed using absorbance measurements. AC16 cardiomyocytes were then exposed to varying doses of AGEs, resulting in dose-dependent decreases in cell viability. The maximum tolerated dose of AGEs was determined, revealing significant downregulation of the cardiac gene gap junction alpha 1 (GJA1). Furthermore, the study assessed the effects of AGEs, glucose shock, and their combination on biomarkers, cardiac myosin heavy chain (MHC), and connexin-43 (Cx-43) in AC16 cells. It was found that AGEs supplementation induced an increase in MHC expression while reducing Cx-43 expression, potentially contributing to cardiac dysfunction. Glucose shock also affected cardiomyocyte contractility, highlighting the complex interplay between AGEs, glucose levels, and cardiac function. Additionally, human iPSC-derived cardiomyocytes were subjected to varying doses of AGEs, revealing dose-dependent cytotoxicity and alterations in contractility. Immunostaining confirmed upregulation of MYH7, a cardiac gene associated with muscle contraction, in response to AGEs. However, the expression of Cx-43 was minimal in these cells. This comprehensive investigation sheds light on the intricate relationship between AGEs, glucose shock, and cardiomyocyte function, providing insights into potential mechanisms underlying cardiac dysfunction associated with metabolic disorders such as diabetic cardiomyopathy (DCM).

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Of cells and tissues: Identifying the elements of a diabetic cardiac in vitro study model

Hernandez,

Gobinath,

Padilla

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Inhibition of ERK 1/2 pathway downregulates YAP1/TAZ signaling in human cardiomyocytes exposed to hyperglycemic conditions

Cited by 1 publication

References 24 publications

Of cells and tissues: Identifying the elements of a diabetic cardiac in vitro study model

Of cells and tissues: Identifying the elements of a diabetic cardiac in vitro study model

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