Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress

Acta Pharmacologica Sinica
Wen-ting YouYue Gao

Abstract

CYP2J3 in myocardium metabolizes arachidonic acid to 4 regioisomeric epoxyeicosatrienoic acids (EETs), which have diverse biological activities in rat heart. In this study we examined whether CYP2J3 was involved in cardioprotective effects of ophiopogonin D (OPD), a steroidal glycoside isolated from Chinese herb Radix ophiopogonis. Rat cardiomyoblast cell line (H9c2 cells) was tested. Intracellular Ca(2+) concentrations ([Ca(2+)]i) were measured using Fluo-4/AM. The expression of calcium-regulating molecules and ER stress signaling molecules was measured with qRT-PCR and Western blot analyses. Cell apoptosis was quantified with Hoechst 33258 staining and TUNEL assay. The level of 14,15-DHET, a stable metabolite of 14,15-EET, was assessed with ELISA. Angiotensin II (10(-6) mol/L) significantly decreased the expression of calcium-regulating molecules (SERCA2a, PLB, RyR2 and FKBP12.6), and elevated [Ca(2+)]i in H9c2 cells. Furthermore, angiotensin II markedly increased the expression of ER stress signaling molecules (GRP78, CHOP, p-JNK and cleaved caspase-12) and ER stress-mediated apoptosis. OPD (100, 250 and 500 nmol/L) dose-dependently increased CYP2J3 expression and 14,15-DHET levels in normal H9c2 cells. Pretreatment of H9c2 ...Continue Reading

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Citations

Aug 25, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Xin HuangSanyuan Hu
May 27, 2020·Journal of Cellular Physiology·Xiao-Qin LuoCha-Xiang Guan
Mar 29, 2019·Oxidative Medicine and Cellular Longevity·Xinyu YangHongcai Shang
Sep 3, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Karen M WagnerBruce D Hammock
Jan 26, 2021·Oxidative Medicine and Cellular Longevity·Jia WangYue Gao
Apr 27, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Han LiYue Gao
May 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ivo Ricardo de Seabra Rodrigues DiasLiang Liu

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