Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways

Ba, Lina; Gao, Jingli; Chen, Yunping; Qi, Hanping; Chen, Dong; Pan, Hao; Zhang, Qianhui; Shi, Pilong; Song, Chao; Guan, Xueying; Cao, Yonggang; Sun, Hai‐Ying

doi:10.1016/j.phymed.2018.11.025

Cited by 128 publications

(93 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The activation ERK1/2 is related to myocardial apoptosis, and the inhibition of ERK1/2 is beneficial for cardiac functional recovery. 33) In the present study, we found that compared with t-BHP group, DEX-018 group exhibited significantly increased protein phosphorylation of Akt and decreased protein phosphorylation of ERK1/2, suggesting that the protective effect of DEX-018 was at least partly due to its ability to regulate the PI3K/Akt and ERK1/2 signaling pathways. Our results clearly demonstrated that DEX-018 plus LY294002 (PI3K inhibitor) group and DEX-018 plus MK2206 (Akt inhibitor) group significantly diminished the protective role of DEX-018, further confirming the role of the PI3K/Akt pathway in mediating the protective effect of DEX-018 against t-BHP induced oxidative injury in HUVECs.…”

Section: Discussionsupporting

confidence: 51%

Cytoprotective Effects Evaluation of a Novel Danshensu Derivative DEX-018 against Oxidative Stress Injury in HUVECs

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Ischemic heart disease (IHD) is one of the most common cardiovascular diseases with high morbidity and mortality. Danshensu (DSS) is widely used in the treatment of coronary heart disease. In this study, the carboxy group of DSS was esterified with edaravone to synthesize the novel DSS derivative DEX-018 to achieve a synergistic protective effect and overcome the structural deficiency of DSS. The pharmacological effect of DEX-018 against tert-butyl hydrogen peroxide (t-BHP) induced oxidative damage in human umbilical vein endothelial cells (HUVECs) was evaluated. The results demonstrated that pretreatment with DEX-018 significantly increased cell viability and superoxide dismutase (SOD) activity and decreased the lactate dehydrogenase (LDH) leakage rate, malondialdehyde (MDA) level and intracellular reactive oxygen species (ROS) level. In addition, DEX-018 inhibited cell apoptosis and reversed the expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) in HUVECs stimulated by t-BHP. Further study on the mechanism of DEX-018 revealed that the expression of p-Akt and p-extracellular signal-regulated kinase 1/2 (ERK1/2) was increased, which suggested that DEX-018 may protect HUVECs against t-BHP induced oxidative injury via the Akt and ERK1/2 signaling pathways. To further validate the correlation, CCK8 was used to detect cell viability after treatment with DEX-018 plus Akt inhibitor (MK2206) and PI3K inhibitor (LY294002). Compared with DEX-018 alone, MK2206 or LY294002 significantly decreased cell viability of HUVECs, indicating that the protective effect of DEX-018 against t-BHP induced oxidative injury was significantly weakened. It was further verified that the antioxidant and anti-apoptotic effects of DEX-018 were partly related to the phosphadylinositol 3-kinase (PI3K)/Akt signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 51%

Cytoprotective Effects Evaluation of a Novel Danshensu Derivative DEX-018 against Oxidative Stress Injury in HUVECs

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…During the formation of autophagosomes, cytosolic LC3-I is conjugated to phosphatidylethanolamine to generate LC3-II, which is recruited to the autophagosomal membrane and degraded followed by the fusion of autophagosomes to lysosomes, thus, the LC3-II/LC3-I ratio is a marker of autophagy activity. It has been found that changes in autophagosome-lysosomal pathway activity have key pathogenic effects in cardiac hypertrophy (Ba et al, 2019). Autophagy at the normal levels protects cardiomyocytes from environmental stimuli, but autophagy imbalance can lead to cardiac hypertrophy (Xie et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

Tang

Zheng

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background It has been confirmed that mutations in solute carrier family 26 member 4 (SLC26A4) contribute to pendred syndrome. However, the role of SLC26A4 in cardiac hypertrophy and the signaling pathways remain unclear. Methods Cardiomyocytes were treated by 200 µM phenylephrine (PE) to induce cardiac hypertrophy. Also, the expression of SLC26A4, GSK3, cardiac hypertrophy markers including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected through real-time quantitative polymerase chain reaction (RT-qPCR). Flow cytometry assay was used to test the apoptosis of PE-induced cardiomyocytes transfected by small interfere RNA (siRNA)-SLC26A4. Furthermore, we detected the expression of autophagy-related markers including light chain 3 (LC3) and P62. Finally, we established a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy in vivo. Results RT-qPCR results showed that the mRNA expression of SLC26A4 was significantly up-regulated in PE-induced cardiac hypertrophy. After inhibiting SLC26A4, the release of ANP and BNP was significantly decreased and GSK3β was elevated in vivo and in vitro. Furthermore, inhibiting SLC26A4 promoted apoptosis of cardiac hypertrophy cells. In addition, LC3 was down-regulated and P62 was enhanced after transfection of siRNA-SLC26A4. Conclusion Our findings revealed that SLC26A4 increases cardiac hypertrophy, and inhibiting SLC26A4 could decrease the release of ANP/BNP and promote the expression of GSK-3β in vitro and in vivo. Moreover, SLC26A4 silencing inhibits autophagy of cardiomyocytes and induces apoptosis of cardiomyocytes. Therefore, SLC26A4 possesses potential value to be a therapeutic target of cardiac hypertrophy, and our study provides new insights into the mechanisms of cardiac hypertrophy.

show abstract

“…The regulation of PI3K/Akt/mTOR and MEK/ERK pathways can lead to the activation of autophagy in HeLa cells (46). In contrast, Ba et al demonstrated that allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR/ERK signaling pathway (47). We therefore expected that regulation of autocrine/paracrine GnRH expression could activate the Akt/ERK pathways, thus inhibiting cell proliferation by inducing cell apoptosis and autophagy in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer

Suo

Chang

et al. 2019

Front. Endocrinol.

View full text Add to dashboard Cite

Gonadotropin-releasing hormone (GnRH) has been demonstrated to exert anti-proliferative functions on various tumor cells in endometrial, ovarian, bladder, or prostate cancer as a part of the autocrine system. In addition, the expression levels of GnRH and its receptor had been identified in breast cancer or non-reproductive cancers, such as glioblastoma and pancreatic cancer. Previous studies have reported abnormal GnRH expression in several malignant tumors, suggesting that GnRH and its receptor might be essential for tumourigenesis. In the present study, we attempted to clarify the mechanisms underlying GnRH function in cell proliferation in pancreatic cancer. Our results indicated that GnRH expression might be essential for the malignancy of pancreatic cancer. We then found that GnRH overexpression can induce cell apoptosis through activating the Bcl-2/Bax pathway and autophagy might be involved in the GnRH-mediated apoptosis in Panc1 cells. Further investigation showed that the inhibition of GnRH may promote tumor invasion and migration through upregulation of MMP2 expression in pancreatic cancer cells. Moreover, our results indicated that GnRH can regulate the Akt/ERK1/2 pathways to promote cell proliferation by inhibiting cell apoptosis in Panc1 cells. Therefore, our finding exhibited that the regulation of GnRH expression may be essential for tumourigenesis in pancreatic cancer, and might be a potential target for the treatment of the patients with pancreatic cancer.

show abstract

Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways

Cited by 128 publications

References 41 publications

Cytoprotective Effects Evaluation of a Novel Danshensu Derivative DEX-018 against Oxidative Stress Injury in HUVECs

Cytoprotective Effects Evaluation of a Novel Danshensu Derivative DEX-018 against Oxidative Stress Injury in HUVECs

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer

Contact Info

Product

Resources

About