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Fas/FasL-mediated cell death in rat's diabetic hearts involves activation of calcineurin/NFAT4 and is potentiated by a high-fat diet rich in corn oil.
Eid, Refaat A; Alkhateeb, Mahmoud A; Eleawa, Samy M; Zaki, Mohamed Samir Ahmed; El-Kott, Attalla Farag; El-Sayed, Fahmy; Otifi, Hassan; Alqahtani, Sultan; Asiri, Ziad A; Aldera, Hussain.
Afiliación
  • Eid RA; Department of Pathology, College of Medicine, King Khalid University, P.O. 641, Abha,61421, Saudi Arabia. Electronic address: refaat_eid@yahoo.com.
  • Alkhateeb MA; Department of basic medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia.
  • Eleawa SM; Department of Applied Medical Sciences, College of Health Sciences, PAAET, Shuwaikh, Kuwait.
  • Zaki MSA; Department of Anatomy, College of Medicine, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia; Department of Histology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
  • El-Kott AF; Department of Biology, College of Science, King Khalid University, P.O. 641, Abha, 61421, Saudi Arabia; Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt.
  • El-Sayed F; Department of Pathology, College of Medicine, King Khalid University, P.O. 641, Abha,61421, Saudi Arabia.
  • Otifi H; Department of Pathology, College of Medicine, King Khalid University, P.O. 641, Abha,61421, Saudi Arabia.
  • Alqahtani S; Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt.
  • Asiri ZA; Department of clinical biochemistry, Central Laboratory Department, Asser central Hospital, Abha, Saudi Arabia.
  • Aldera H; Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt.
J Nutr Biochem ; 68: 79-90, 2019 06.
Article en En | MEDLINE | ID: mdl-31030170
This study investigated if calcineurin/nuclear factor of activated T cells (NFAT) axis mediates the cardiac apoptosis in rats with type 1 diabetes mellitus (T1DM)-induced rats or administered chronically high-fat diet rich in corn oil (CO-HFD). Also, it investigated the impact of chronic administration of CO-HFD on Fas/Fas ligand (Fas/FasL)-induced apoptosis in the hearts of T1DM-induced rats. Adult male Wistar rats (140-160 g) were classified as control: (10% fat) CO-HFD: (40% fat), T1DM, and T1DM + CO-HFD (n=20/each). In vitro, cardiomyocytes were cultured in either low glucose (LG) or high glucose (HG) media in the presence or absence of linoleic acid (LA) and other inhibitors. Compared to the control, increased reactive oxygen species (ROS), protein levels of cytochrome C, cleaved caspase-8 and caspase-3, myocardial damage and impeded left ventricular (LV) function were observed in the hearts of all treated groups and maximally in T1DM + CO-HFD-treated rats. mRNA of all NFAT members (NFAT1-4) were not affected by any treatment. CO-HFD or LA significantly up-regulated Fas levels in both LVs and cultured cardiomyocytes in a ROS dependent mechanism and independent of modulating intracellular Ca2+ levels or calcineurin activity. T1DM or hyperglycemia significant up-regulated mRNA and protein levels of Fas and FasL by activating Ca2+/calcineurin/NFAT-4 axis. Furthermore, Fas/FasL cell death induced by recombinant FasL (rFasL) or HG media was enhanced by pre-incubating the cells with LA. In conclusion, activation of the Ca2+/calcineurin/NFAT4 axis is indispensable for hyperglycemia-induced Fas/FasL cell death in the cardiomyocytes and CO-HFD sensitizes this by up-regulation of Fas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Dieta Alta en Grasa / Miocardio Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: J Nutr Biochem Asunto de la revista: BIOQUIMICA / CIENCIAS DA NUTRICAO Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Dieta Alta en Grasa / Miocardio Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: J Nutr Biochem Asunto de la revista: BIOQUIMICA / CIENCIAS DA NUTRICAO Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos