Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway

ZHANG Zhi-ying; LIU Chao; WANG Peng-xiang; HAN Yi-wei; ZHANG Yi-wen; HAO Mei-li; SONG Zi-xu; ZHANG Xiao-ying

doi:10.1007/s11655-022-3687-4

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Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway

Original Article | Updated：2023-04-27

- Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway
- Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway
- 中国结合医学杂志（英文版） 2023年29卷第5期页码：434-440
- Affiliations：
  
  1.Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi Province (712082), China
  2.Key Laboratory of High Altitude Environment and Gene Related to Disease of Tibet Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi Province(712082), China
  3.School of Finance Economics, Xizang Minzu University, Xianyang, Shaanxi Province (712082), China
  4.School of Information Engineering, Xizang Minzu University, Xianyang, Shaanxi Province (712082), China
- Author bio：
  
  Dr. ZHANG Xiao-ying, E-mail:zzy20210726@163.com
- Funds：
  
  Science Foundation of Education Department of Shaanxi Provincial Government(19JK0890);Natural Science Foundation of Xizang (Tibet) Autonomous Region(XZ202001ZR0089G);Major Training Project of Xizang Minzu University(18MDZ03;20MDT03);Funded Project of Young Scholar Cultivation Program of Xizang Minzu University(21MDX04)
- DOI：10.1007/s11655-022-3687-4
  中图分类号：
- 纸质出版日期：2023-05，
  
  网络出版日期：2022-12-07，
  
  录用日期：2022-06-29
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Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway[J]. 中国结合医学杂志（英文版）, 2023,29(5):434-440.

ZHANG Zhi-ying, LIU Chao, WANG Peng-xiang, et al. Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(5):434-440.
Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway[J]. 中国结合医学杂志（英文版）, 2023,29(5):434-440. DOI： 10.1007/s11655-022-3687-4.

ZHANG Zhi-ying, LIU Chao, WANG Peng-xiang, et al. Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway[J]. Chinese Journal of Integrative Medicine, 2023,29(5):434-440. DOI： 10.1007/s11655-022-3687-4.

摘要

Abstract

Objective:

To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation

apoptosis

and autophagy.

Methods:

H9C2 cells were randomly divided into 7 groups

namely control

model

EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector)

IV (circHIPK3 interference)

Dmy (50 μmol/L)

Dmy+IV

and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry

respectivley. Western blot was used to evaluate the levels of light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ)

phospho-phosphoinositide 3-kinase (p-PI3K)

protein kinase B (p-AKT)

and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.

Results:

Compared to H9C2 cells

the expression of circHIPK in H9C2 hypoxia model cells increased significantly (

0.05). Compared to the control group

the cell apoptosis and autophagosomes increased

cell proliferation rate decreased significantly

and the expression of LC3Ⅱ/Ⅰ significantly increased (all

0.05). Compared to the model group

the rate of apoptosis and autophagosomes in IV

Dmy

and Dmy+IV group decreased

the cell proliferation rate increased

and the expression of LC3Ⅱ/Ⅰ decreased significantly (all

0.05). Compared to the control group

the expressions of p-PI3K

p-AKT

and p-mTOR in the model group significantly reduced (

0.05)

whereas after treatment with Dmy and sh-circHIPK3

the above situation was reversed (

0.05).

Conclusion:

Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy

and the mechanism may be related to PI3K/AKT/mTOR pathway.

关键词

Keywords

dihydromyricetincircHIPKautophagycell apoptosisPI3K/AKT/mTOR

references

DeFilippis AP, Chapman AR, Mills NL, de Lemos JA, Arbab-Zadeh A, Newby LK, et al. Assessment and treatment of patients with type 2 myocardial infarction and acute nonischemic myocardial injury. Circulation 2019;140:1661-1678.

Hubbi ME, Semenza GL. Regulation of cell proliferation by hypoxia-inducible factors. Am J Physiol Cell Physiol 2015;309:C775-C782.

Lu L, Liu M, Sun R, Zheng Y, Zhang P. Myocardial infarction: symptoms and treatments. Cell Biochem Biophys 2015;72:865-867.

Huang SL, Li XZ, Zheng H, Si XY, Li B, Wei GQ, et al. Loss of super-enhancer-regulated circRNA N fix induces cardiac regeneration after myocardial infarction in adult mice. Circulation 2019;139:2857-2876.

Guo ZX, Zhou FZ, Song W, Yu LL, Yan WJ, Yin LH, et al. Suppression of microRNA-101 attenuates hypoxia-induced myocardial H9c2 cell injury by targeting DIMT1-Sp1/survivin pathway. Eur Rev Med Pharmacol Sci 2018;22:6965-6976.

Wang K, Gan TY, Li N, Liu CY, Zhou LY, Gao JN, et al. Circular RNA mediates cardiomyocyte death via miRNA-dependent upregulation of MTP18 expression. Cell Death Differ 2017;24:1111-1120.

Garikipati VNS, Verma SK, Cheng ZJ, Liang DM, Truongcao MM, Cimini M, et al. Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis. Nat Commun 2019;10:4317.

Han D, Wang Y, Wang Y, Dai X, Zhou T, Chen J, et al. The tumor-suppressive human circular RNA CircITCH sponges miR-330-5p to ameliorate doxorubicin-induced cardiotoxicity through upregulating SIRT6, survivin, and SERCA2a. Circ Res 2020;127:e108-e125.

Lei D, Wang Y, Zhang L, Wang Z. Circ_0010729 regulates hypoxia-induced cardiomyocyte injuries by activating TRAF5 via sponging miR-27a-3p. Life Sci 2020;262:118511.

Wang Y, Zhao R, Liu W, Wang Z, Rong J, Long X, et al. Exosomal circHIPK3 released from hypoxia-pretreated cardiomyocytes regulates oxidative damage in cardiac microvascular endothelial cells via the miR-29a/IGF-1 pathway. Oxid Med Cell Longev 2019;2019:7954657.

Chen X, Mao R, Su W, Yang X, Geng Q, Guo C, et al. Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer. Autophagy 2020;16:659-671.

Liu D, Mao Y, Ding L, Zeng XA. Dihydromyricetin: a review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability. Trends Food Sci Technol 2019;91:586-597.

Zhang J, Chen Y, Luo H, Sun L, Xu M, Yu J, et al. Recent update on the pharmacological effects and mechanisms of dihydromyricetin. Front Pharmacol 2018;9:1204.

Zhang X, Wang L, Peng L, Tian X, Qiu X, Cao H, et al. Dihydromyricetin protects HUVECs of oxidative damage induced by sodium nitroprusside through activating PI3K/Akt/FoxO3a signalling pathway. J Cell Mol Med 2019;23:4829-4838.

Liu S, Ai Q, Feng K, Li Y, Liu X. The cardioprotective effect of dihydromyricetin prevents ischemia-reperfusion-induced apoptosis in vivo and in vitro via the PI3K/Akt and HIF-1α signaling pathways. Apoptosis 2016;21:1366-1385.

Tan M, Jiang B, Wang H, Ouyang W, Chen X, Wang T, et al. Dihydromyricetin induced lncRNA MALAT1-TFEB-dependent autophagic cell death in cutaneous squamous cell carcinoma. J Cancer 2019;10:4245-4255.

Gong L, Xu H, Zhang X, Zhang T, Shi J, Chang H. Oridonin relieves hypoxia-evoked apoptosis and autophagy via modulating microRNA-214 in H9c2 cells. Artif Cells Nanomed Biotechnol 2019;47:2585-2592.

Liu X, Deng Y, Xu Y, Jin W, Li H. MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1. J Mol Cell Cardiol 2018;118:133-146.

Wu JZ, Ardah M, Haikal C, Svanbergsson A, Diepenbroek M, Vaikath NN, et al. Dihydromyricetin and salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy. Transl Neurodegener 2019;15:18.

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak AN, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013;495:333-338.

Panni S, Lovering RC, Porras P, Orchard S. Non-coding RNA regulatory networks. Biochim Biophys Acta Gene Regul Mech 2020;1863:194417.

Nakamura S, Yoshimori T. New insights into autophagosome-lysosome fusion. J Cell Sci 2017;130:1209-1216.

Napoletan F, Baron O, Vandenabeele P, Mollereau B, Fanto M. Intersections between regulated cell death and autophagy. Trends Cell Biol 2019;29:323-338.

Su T, Wang FS. Relationship between PI3K/Akt/mTOR signaling pathway and autophagy and tumor. Chin J Biochem Mol Biol 2016;32:1192-1196.

Guo L, Tan K, Luo Q, Bai X. Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy. Bosn J Basic Med Sci 2020;20:372-380.

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