三碘甲腺原氨酸对缺氧/复氧致乳小鼠心室肌细胞钙离子通道异常的影响及其信号通路机制

Abstract
Figure/Table
References (20)
Related Citation (8)

Download: PDF (913 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To observe the effect of triiodothyronine (T3) on abnormal calcium channels in ventricular myocytes of hypoxia/reoxygenation (H/R) lactating mice and the role of PI3K/Akt signaling pathway in it. Methods Isolation of ventricular myocytes from neonatal mice and establishment of cell H/R model were carried out. Normal control (Control) group, H/R group, T3+H/R group, T3+H/R+LY294002 (LY) group and H/R+LY group were set up. Patch clamp technique was used to observe the changes of L-type calcium channel current (ICaL) and Western blot was used to detect the expression of PI3K/Akt signaling pathway in cardiomyocytes. Results Compared with control group, the peak current of ICaL in H/R group decreased (P < 0.01) and I-V curve moved up. Compared with H/R group, ICaL peak current increased in T3+H/R group (P < 0.01), and decreased in H/R+LY group (P < 0.01). Compared with T3+H/R group, ICaL peak current decreased in T3+H/R+LY group (P < 0.01). Compared with control group, V1/2 in H/R group decreased significantly (P < 0.05), inactivation curve shifted to the right and inactivation slowed down. Compared with H/R group, V1/2 of T3+H/R group increased (P < 0.05), the inactivation curve moved left, and the inactivation accelerated. Compared with control group, V1/2 of H/R group increased (P < 0.05), the activation curve moved left, and the activation accelerated. Compared with H/R group, V1/2 of T3+H/R group decreased (P < 0.05), the activation curve moved right and the activation slowed down. Compared with control group, the expression of P-PI3K and P-Akt decreased in H/R group (P < 0.01). Compared with H/R group, the expression of P-PI3K and P-Akt in myocardial cells of T3+H/R group increased (P < 0.01), while the expression of P-PI3K and P-Akt in myocardial cells of H/R+LY group decreased (P < 0.01). Compared with T3+H/R group, the expression of P-PI3K and P-Akt in myocardial cells of T3+H/R+LY group decreased (P < 0.01). Conclusion ICaL current decreases when cardiomyocyte H/R, affecting excitation and contraction of cardiomyocyte. T3 can protect L-type calcium channel by activating PI3K/Akt signaling pathway and reduce the decrease of channel current, thus exerting its cardioprotective effect.

Key words： Thyroid hormone Ventricular cardiomyocytes Hypoxia/reoxygenation L-type calcium channel

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	LIU Lei ZENG Bin LIAO Xiaoting

Cite this article:

LIU Lei ZENG Bin LIAO Xiaoting. Effect of triiodothyronine on abnormal calcium channel in ventricular myocytes of hypoxia/reoxygenation-induced lactating mice and its signaling pathway mechanism[J]. 中国医药导报, 2019, 16(29): 11-15.

URL:

http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2019/V16/I29/11

[1] Henderson KK，Danzi S，Paul JT，et al. Physiological replacement of T3 improves left ventricular function in an animal model of myocardial infarction-induced congestive heart failure [J]. Circ Heart Fail，2009，2（3）：243-252.
[2] Forini F，Lionetti V，Ardehali H，et al. Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodelling in rats [J]. J Cell Mol Med，2011，15（3）：514-524.
[3] Jiao S，Zhu H，He P，et al. Betulinic acid protects against cerebral ischemia/reperfusion injury by activating the PI3K/Akt signaling pathway [J]. Biomed Pharmacother，2016， 84：1533-1537.
[4] Ehler E，Moore-Morris T，Lange S. Isolation and culture of neonatal mouse cardiomyocytes [J]. J Vis Exp，2013，6（79）：e50154.
[5] Graves BM，Simerly T，Li C，et al. Phosphoinositide-3-kinase/akt - dependent signaling is required for maintenance of Ca2+i，ICa，and Ca2+ transients in HL-1 cardiomyocytes [J]. J Biomed Sci，2012，19（1）：1-9.
[6] Eltzschig HK，Eckle T. Ischemia and reperfusion--from mechanism to translation [J]. Nat Med，2011，17（11）：1391-1401.
[7] Kalogeris T，Bao Y，Korthuis RJ. Mitochondrial reactive oxygen species：a double edged sword in ischemia/reperfusion vs preconditioning [J]. Redox Biol，2014，2：702-714.
[8] Bers DM. Cardiac sarcoplasmic reticulum calcium leak：basis and roles in cardiac dysfunction [J]. Annu Rev Physiol，2014，76（1）：107-127.
[9] Hegyi B. Complex electrophysiological remodeling in postinfarction ischemic heart failure [J]. Proc Natl Acad Sci USA，2018，115：E3036-E3044.
[10] 郑杨，佟倩，张文杰.卡托普利对H/R乳鼠心室肌细胞游离钙的影响及其离子通道机制[J].中国病理生理杂志，2006，22（9）：1693-1697.
[11] Gambardella J，Trimarco B，Iaccarino G，et al. New insights in cardiac calcium handling and excitation-contraction coupling [J]. Adv Exp Med Biol，2018，1067：373-385.
[12] Kronenbitter A，Funk F，Hackert K，et al. Impaired Ca2+ cycling of nonischemic myocytes contributes to sarcomere dysfunction early after myocardial infarction [J]. J Mol Cell Cardiol，2018，119：28-39.
[13] Rajagopalan V，Zhang Y，Ojamaa K，et al. Safe oral triiodo-l-thyronine therapy protects from post-infarct cardiac dysfunction and arrhythmias without cardiovascular adverse effects [J]. PLoS One，2016，11（3）：e0151413.
[14] Eber B，Schumacher M，Langsteger W，et al. Changes in thyroid hormone parameters after acute myocardial infarction [J]. Cardiology，1995，86（2）：152-156.
[15] Adamopoulos S，Gouziouta A，Mantzouratou P，et al. Thyroid hormone signaling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices：potential physiological consequences? [J]. Interact Cardiovasc Thorac Surg，2013，17（4）：664-668.
[16] Mourouzis I，Mantzouratou P，Galanopoulos G，et al. Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance：potential involvement of Akt and ERK signaling [J]. Mol Cell Biochem，2012，363（1/2）：235-243.
[17] da Silva IB，Gomes DA，Alenina N，et al. Cardioprotective effect of thyroid hormone is mediated by AT2 receptor and involves nitric oxide production via Akt activation in mice [J]. Heart Vessels，2001，33（6）：671-681.
[18] Yasuda J，Okada M，Yamawaki H. T3 peptide，an active fragment of tumstatin，inhibits H2O2-induced apoptosis in H9c2 cardiomyoblasts [J]. Eur J Pharmacol，2017， 807：64-70.
[19] Granato M，Rizzello C，Gilardini Montani MS，et al. Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways [J]. J Nutr Biochem，2017，41：124-136.
[20] Rota M，Boni A，Urbanek K，et al. Nuclear targeting of akt enhances ventricular function and myocyte contractility [J]. Circ Res，2005，97（12）：1332-1341.