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β 3 ‐ Adrenergic Receptor Activation and Endoplasmic Reticulum Stress via Modulation of Intracellular Free Zn 2 + in Hyperglycemic Cardiomyocytes
Author(s) -
Turan Belma,
Tuncay Erkan,
Toy Aysegul,
Cicek Figen
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.951.2
Subject(s) - intracellular , endoplasmic reticulum , endocrinology , medicine , stimulation , chemistry , ryanodine receptor , receptor , biology , biochemistry
Beta‐adrenergic receptor (β‐AR)‐signaling plays important role in normal cardiac function while β 3 ‐AR activation depresses cardiac contractile force. Since intracellular free Zn 2 + releases are originated either from metallothionin‐nitrolisation or endoplasmic reticulum (ER) and disturbing excitation‐contraction cyclying in cardiomyocytes, we examined role of β 3 ‐AR activation on modulation of intracellular free Zn 2 + and ER stress (ERS) in hyperglycemic cardiomyocytes. Protein and mRNA levels of β 3 ‐AR were increased in diabetic cardiomyocytes being associated with depressed left ventricular developed pressure. β 3 ‐AR stimulation with BRL37344 induced significant increase in intracellular free Zn 2 + in diabetic cardiomyocytes which was diminished either with NOS inhibitor L‐NAME or β 3 ‐AR antagonist SR59230 while it was further increased with non‐selective β‐blocker nadolol. Additionally, either BRL37344 or NO‐donor SNP induced significant increases in intracellular free Zn 2 + in normal cardiomyocytes while they were diminished either with L‐NAME or ODQ. These data are strongly demonstrated an association between increased intracellular free Zn 2 + and β 3 ‐AR activation in diabetic cardiomyocytes. BRL37344 stimulation of only diabetic cardiomyocytes presented also marked increases in ERS‐associated proteins which are very similar to those of diabetics. Taken together, our data demonstrated that β 3 ‐AR activation in cardiomyocytes under hyperglycemia induces marked increase in intracellular free Zn 2 + which seems to be closely related with ERS, thereby both actions can underlie the depressed cardiac function in diabetics. (Supported by TUBITAK‐SBAG‐113S466)