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Eicosapentaenoic Acid Rescues L-Type Ca2+ Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes
Version 1
: Received: 30 April 2024 / Approved: 30 April 2024 / Online: 30 April 2024 (08:17:49 CEST)
How to cite:
Morishima, M.; Wang, P.; Horii, K.; Horikawa, K.; Ono, K. Eicosapentaenoic Acid Rescues L-Type Ca2+ Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes. Preprints2024, 2024041965. https://doi.org/10.20944/preprints202404.1965.v1
Morishima, M.; Wang, P.; Horii, K.; Horikawa, K.; Ono, K. Eicosapentaenoic Acid Rescues L-Type Ca2+ Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes. Preprints 2024, 2024041965. https://doi.org/10.20944/preprints202404.1965.v1
Morishima, M.; Wang, P.; Horii, K.; Horikawa, K.; Ono, K. Eicosapentaenoic Acid Rescues L-Type Ca2+ Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes. Preprints2024, 2024041965. https://doi.org/10.20944/preprints202404.1965.v1
APA Style
Morishima, M., Wang, P., Horii, K., Horikawa, K., & Ono, K. (2024). Eicosapentaenoic Acid Rescues L-Type Ca<sup>2+</sup> Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes. Preprints. https://doi.org/10.20944/preprints202404.1965.v1
Chicago/Turabian Style
Morishima, M., Kazuki Horikawa and Katsushige Ono. 2024 "Eicosapentaenoic Acid Rescues L-Type Ca<sup>2+</sup> Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes" Preprints. https://doi.org/10.20944/preprints202404.1965.v1
Abstract
Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.
Medicine and Pharmacology, Dietetics and Nutrition
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
