Gökçe Yasin, Erkan Orhan, Savaş Kamil, Rahman Taufiq, Yaraş Nazmi
Department of Biophysics, School of Medicine, Sanlıurfa, 63300, Turkey.
Department of Biophysics, School of Medicine, Antalya, 07070, Turkey.
Biochem Biophys Res Commun. 2022 Jun 25;610:56-60. doi: 10.1016/j.bbrc.2022.04.031. Epub 2022 Apr 13.
The store-operated Ca entry (SOCE) represents an important route for generating cellular Ca signals that are implicated in physiological and various pathological scenarios that include diabetic cardiomyopathy (DM-CMP) which is well known to have Ca dysregulation among other salient features. In this study, we investigated the role of SOCE in Ca handling of cardiomyocytes obtained from adult male Wistar rats that were made diabetic by intraperitoneal administration of streptozotocin (STZ 50 mg/kg). We also included another group of rats with diabetes induced by STZ administration but received an angiotensin II receptor blocker - losartan. In whole cell recordings with isolated cardiomyocytes, the SOCE-representative whole-cell current I was found to be significantly reduced for the diabetic group compared to the control group and chronic losartan treatment could restore I to a level comparable to the control group. However, in contrast to the observed reduction in I, Orai1 and Orai3 proteins were found to be significantly upregulated in diabetic condition whereas no significant change in the expression levels of Stim1, Stim2 and Orai2 was observed. Also, losartan treatment did not affect the expression pattern of these key proteins for SOCE in diabetic group. The observed imbalance between the functional read out of SOCE (peak I size) and expression levels of the underlying proteins was puzzling but could be, among other possibilities, due to impairment of interaction between Stim and Orai proteins. We argue that the observed changes in SOCE with diabetes could be a contributing factor for the Ca dyshomeostasis associated with diabetic cardiomyopathies and blockade of angiotensin II receptor may potentially restore normal SOCE in diabetic cardiomyocytes.
store-operated Ca entry (SOCE)是产生细胞Ca信号的重要途径，其与包括糖尿病性心肌病（DM-CMP）在内的生理和各种病理情况有关，众所周知，糖尿病性心肌病除其他显著特征外还存在Ca调节异常。在本研究中，我们调查了SOCE在成年雄性Wistar大鼠心肌细胞Ca处理中的作用，这些大鼠通过腹腔注射链脲佐菌素（STZ 50mg/kg）诱导糖尿病。我们还纳入了另一组通过STZ给药诱导糖尿病但接受血管紧张素II受体阻滞剂——氯沙坦的大鼠。在分离的心肌细胞的全细胞记录中，发现糖尿病组的SOCE代表性全细胞电流I与对照组相比显著降低，而氯沙坦的长期治疗可将I恢复到与对照组相当的水平。然而，与观察到的I降低相反，在糖尿病状态下发现Orai1和Orai3蛋白显著上调，而Stim1、Stim2和Orai2的表达水平未观察到显著变化。此外，氯沙坦治疗不影响糖尿病组中这些SOCE关键蛋白的表达模式。SOCE的功能读数（峰值I大小）与基础蛋白表达水平之间观察到的失衡令人困惑，但在其他可能性中，这可能是由于Stim和Orai蛋白之间相互作用的受损。我们认为，糖尿病中观察到的SOCE变化可能是与糖尿病性心肌病相关的Ca稳态失衡的一个促成因素，血管紧张素II受体的阻断可能潜在地恢复糖尿病心肌细胞中的正常SOCE。
