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The Role of Cross‐links Between Endoplasmic Reticulum Stress, Oxidative stress and Mitochondrial dysfunction in Cardiomyocytes and H9c2 Cells under Hyperglycemia
Author(s) -
HAFEZ GAYE,
TUNCAY ERKAN,
TOY Aysegul,
TURAN Belma
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1025.5
Subject(s) - endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , oxidative stress , chemistry , intracellular , cytosol , mitochondrion , apoptosis , reactive oxygen species , medicine , endocrinology , biology , biochemistry , enzyme
Under physiological condition, endoplasmic reticulum (ER) is responsible basically from protein synthesis and secretion as well as intracellular Ca 2+ signalling while sarcoplasmic reticulum (SR) plays basical role in excitation‐contraction coupling of cardiomyocytes.A change or differientiation in ER related functions can induced by ER stress via affecting signaling pathways. Various studies showed that the cross‐relations between ER stress, increased ROS/RNS, and mitochondrial (MitC) dysfunction induced cardiomyocyte dysfunction via affecting intracellular free Ca 2+ and Zn 2+ homeostasis. Therefore, we aimed to investigate the cross‐links in cardiomyocytes and H9c2 cells under hyperglycemia, ER‐stress induced by tunicamycin (TM) and increased cytosolic Zn 2+ due to increased ROS/RNS. Freshly isolated ventricular cardiomyocytes from male rats under hypergycemia and increased cytosolic Zn 2+ conditions exibited significant increases in the levels of ER stress chaperon proteins such as GRP78 and calregulin while only hyperglycemia and ER‐stress induced these changes in the levels of calnexin and Gadd153. We also show the levels of those proteins in H9c2 cells after incubation of TM for 18 h. And also, our data show ER and MitC interaction, the levels of PML and some proteins associated with apoptosis as Bcl‐2 and Bax are examined. Furthermore, these conditions induced marked changes in the membrane potential of MitC. These data with functional data demonstrate that increased ROS/RNS observed under these conditions in cardiomyocytes and H9c2 cells underlie both ER stress and MitC dysfunction thereby inducing cardiac dysfunction in diabetic subjects (Supported by TUBITAK‐SBAG 113S466).