Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca 2+ overload in rat cardiomyocytes

Chen, Rongchang; Sun, Guibo; Ye, Jingxue; Wang, Jian; Zhang, Miao-di; Sun, Xiaobo

doi:10.1016/j.toxlet.2017.04.010

Cited by 43 publications

(33 citation statements)

References 48 publications

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“…Emerging evidence suggests that ER stress plays a crucial role in Dox-induced cardiotoxicity [ 12 , 13 ]. Thus, we investigated whether the cardioprotective effects of HC against Dox-induced cardiotoxicity are associated with decreased ER stress.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of TRPA1 Attenuates Doxorubicin‐Induced Acute Cardiotoxicity by Suppressing Oxidative Stress, the Inflammatory Response, and Endoplasmic Reticulum Stress

Wang

Liu

et al. 2018

Oxidative Medicine and Cellular Longevity

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The transient receptor potential ankyrin 1 (TRPA1) channel is expressed in cardiomyocytes and involved in many cardiovascular diseases. However, the expression and function of TRPA1 in doxorubicin- (Dox-) induced acute cardiotoxicity have not been elucidated. This study aimed at investigating whether blocking the TRPA1 channel with the specific inhibitor HC-030031 (HC) attenuates Dox-induced cardiac injury. The animals were randomly divided into four groups: control, HC, Dox, and Dox + HC. Echocardiography was used to evaluate cardiac function, and the heart was removed for molecular experiments. The results showed that the expression of TRPA1 was increased in the heart after Dox treatment. Cardiac dysfunction and increased serum CK-MB and LDH levels were induced by Dox, but these effects were attenuated by HC treatment. In addition, HC mitigated Dox-induced oxidative stress, as evidenced by the decreased MDA level and increased GSH level and SOD activity in the Dox + HC group. Meanwhile, HC treatment lowered the levels of the proinflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α induced by Dox. Furthermore, HC treatment mitigated endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis induced by Dox. These results indicated that inhibition of TRPA1 could prevent Dox-induced cardiomyocyte apoptosis in mice by inhibiting oxidative stress, inflammation, and ER stress.

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Section: Resultsmentioning

confidence: 99%

Inhibition of TRPA1 Attenuates Doxorubicin‐Induced Acute Cardiotoxicity by Suppressing Oxidative Stress, the Inflammatory Response, and Endoplasmic Reticulum Stress

Wang

Liu

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…It is increasingly clear that endoplasmic reticulum stress participated in cardiac dysfunction induced by DOX [ 10 , 11 ]. As Rg1 can inhibit endoplasmic reticulum stress in rat heart [ 17 ], we assume that Rg1 can improve endoplasmic reticulum stress induced by DOX.…”

Section: Discussionmentioning

confidence: 99%

“…type I transmembrane ER-resident protein kinase (PERK), activating transcription factor 6 (ATF6), and Inositol-requiring enzyme 1 (IRE1) [ 9 ]. Recent study has revealed that the perturbation of UPR is implicated in the pathophysiology of doxorubicin-induced cardiotoxicity [ 10 , 11 ]. DOX inactivates glucose-regulated protein 78 (GRP78) leading to the activation of ATF6 and IRE1, then cause cardiomyocyte apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

Liu

et al. 2018

IJMS

103

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Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.

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“…Bicinchoninic acid (BCA) method was used to determine protein concentration. The following Western blotting procedures were carried out as previously described (Chen et al, 2017 ). Proteins were separated on 10 or 8% SDS-PAGE gels and then transferred onto nitrocellulose membranes.…”

Section: Methodsmentioning

confidence: 99%

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

Zhu

Sun

et al. 2018

Front. Physiol.

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Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db−/− (db/db) mice. Low-density lipoprotein cholesterol (LDL-C) and fatty acids (FAs) also decreased in the blood. Higher dose of DZF (1 g·kg−1), but not metformin (0.25 g·kg−1), alleviated hepatic steatosis with reduced liver weight and hepatic lipid accumulation and provided protection from hepatic injury with lower alanine aminotransferase and aspartate aminotransferase and increased hepatic superoxide dismutase activity in db/db mice. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a decrease in FA synthase gene (Fasn) and an increase in FA oxidation gene Ppara expression. Western blot demonstrated that both DZF and metformin activated 5′ AMP-activated protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver. DZF also dramatically improved the ultrastructure of skeletal muscles, AMPK phosphorylation, and GLUT4 translocation. DZF also promoted FA transport and oxidation with Cd36 and Cpt1b up-regulation in the skeletal muscle. In conclusion, DZF improves insulin sensitivity by reducing hepatic lipids through AMPK activation and Notch signal pathway inhibition and enhancing energy metabolism in the skeletal muscle via AMPK. This study provides insights into the treatment of complex conditions, such as IR, where TCM herbal formulas exert multipronged effects through correlating pathways.

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Salvianolic acid B attenuates doxorubicin-induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca 2+ overload in rat cardiomyocytes

Cited by 43 publications

References 48 publications

Inhibition of TRPA1 Attenuates Doxorubicin‐Induced Acute Cardiotoxicity by Suppressing Oxidative Stress, the Inflammatory Response, and Endoplasmic Reticulum Stress

Inhibition of TRPA1 Attenuates Doxorubicin‐Induced Acute Cardiotoxicity by Suppressing Oxidative Stress, the Inflammatory Response, and Endoplasmic Reticulum Stress

Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

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