Tanshinone IIA ameliorates diabetic cardiomyopathy by inhibiting Grp78 and CHOP expression in STZ‑induced diabetes rats

Tao, Shuliang; Chen, Liuyin; Song, Jingmei; Zhu, Ningning; Song, Xueyi; Shi, Ruoli; Ge, Gangfeng; Zhang, Yueming

doi:10.3892/etm.2019.7580

Cited by 17 publications

(13 citation statements)

References 35 publications

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“…Increasing evidence suggesting that ER stress and associated apoptotic cell death are involved in the development of DCM [37][38][39][40]. In the present study, immunoblot analysis revealed significant increases in GRP78 (Fig.…”

Section: Dppi Deletion Prevents Diabetes-induced Endoplasmic Reticulum (Er) Stress As Well As the Associated Er Cell Death Pathwaysupporting

confidence: 68%

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy

Kolpakov

Sikder

Sarkar

et al. 2019

Cell Physiol Biochem

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Section: Dppi Deletion Prevents Diabetes-induced Endoplasmic Reticulum (Er) Stress As Well As the Associated Er Cell Death Pathwaysupporting

confidence: 68%

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy

Kolpakov

Sikder

Sarkar

et al. 2019

Cell Physiol Biochem

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“…Therefore, in order to clarify the mechanism of GAS5 in DCM, STZ-induced diabetic rats and HG-processed H9C2 cells were established. Similar to the results obtained by Tao et al ( 35 ), STZ injection to rat myocardium resulted in decreased body weight and increased blood glucose concentration, indicating successful establishment of diabetic rats. Contrary to the increased expression levels of GAS5 in PBMCs from patients with type 2 diabetes, the present results revealed decreased expression levels of GAS5 both in the rat myocardium and HG-processed H9C2 cells, suggesting that GAS5 expression patterns differ according to the cell types in patients with DM.…”

Section: Discussionsupporting

confidence: 88%

GAS5 regulates diabetic cardiomyopathy via miR‑221‑3p/p27 axis‑associated autophagy

Chen

Zhang

2020

Mol Med Rep

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Diabetic cardiomyopathy (DCM) is one of the primary complications of the cardiovascular system due to diabetes-induced metabolic injury. The present study investigated the autophagy-associated regulatory mechanisms of long non-coding RNAs in cardiac pathological changes in diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were intramyocardially injected and high concentration glucose (HG)-processed H9C2 cells were infected with growth arrest specific transcript 5 (GAS5)-loaded AAV-9 adenovirus. HG-processed H9C2 cells also underwent transfection with small interfering RNA-p27. Hematoxylin and eosin and Masson staining evaluated myocardial histological changes. Quantitative PCR detected the expression levels of GAS5, fibrosis markers (collagen I, collagen III, TGF-β and connective tissue growth factor) and microRNA (miR)-221-3p. Western blotting determined the expression levels of autophagy-associated proteins [microtubule-associated proteins 1A/1B light chain 3B (LC3B) I, LC3B II and p62] and p27. Targetscan7.2 was used to predict binding sites between miR-221-3 and p27. Dual luciferase reporter assayed the effect of miR-221-3p on luciferase activity of GAS5 and p27. GAS5 downregulated high blood glucose concentrations in STZ-induced diabetic rats, however its expression levels decreased in both HG-processed H9C2 cells and the myocardium of DM model rats. GAS5 attenuated the histological abnormalities and reversed the decreased LC3B II and increased p62 expression levels of DM model rats. miR-221-3p mimic suppressed the activity of both GAS5-wild-type (WT) and p27-WT. miR-221-3p expression levels were increased in both HG-processed H9C2 and diabetic myocardium. p27 expression levels decreased following HG but were upregulated by GAS5. sip27 abolished the effect of GAS5 on DCM. GAS5 promoted cardiomyocyte autophagy in DCM to attenuate myocardial injury via the miR-221-3p/p27 axis.

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“…The antihypertensive drugs, such as valsartan, are shown to downregulate CHOP expression and reduce cardiac remodeling in DCM (373,374). On the other hand, phytochemicals, such as matrine, have attracted attention in attenuating maladaptive ERSR (376) and preserving UPR ER signaling (61, 377), subsequently improving cardiac function in STZ-induced DCM. Moreover, vanadium derivative (55) and endogenous hormones, such as melatonin (379) and FGF21 (386,387), have been investigated for their cardioprotective role by suppressing oxidative stress-mediated ERSR and cell death in T2DM.…”

Section: Targeting the Upr Ermentioning

confidence: 99%

Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside

Kaur

Raja

Ruiz-Velasco

et al. 2020

Front. Cardiovasc. Med.

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Heart failure is a serious comorbidity and the most common cause of mortality in diabetes patients. Diabetic cardiomyopathy (DCM) features impaired cellular structure and function, culminating in heart failure; however, there is a dearth of specific clinical therapy for treating DCM. Protein homeostasis is pivotal for the maintenance of cellular viability under physiological and pathological conditions, particularly in the irreplaceable cardiomyocytes; therefore, it is tightly regulated by a protein quality control (PQC) system. Three evolutionarily conserved molecular processes, the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), and autophagy, enhance protein turnover and preserve protein homeostasis by suppressing protein translation, degrading misfolded or unfolded proteins in cytosol or organelles, disposing of damaged and toxic proteins, recycling essential amino acids, and eliminating insoluble protein aggregates. In response to increased cellular protein demand under pathological insults, including the diabetic condition, a coordinated PQC system retains cardiac protein homeostasis and heart performance, on the contrary, inappropriate PQC function exaggerates cardiac proteotoxicity with subsequent heart dysfunction. Further investigation of the PQC mechanisms in diabetes propels a more comprehensive understanding of the molecular pathogenesis of DCM and opens new prospective treatment strategies for heart disease and heart failure in diabetes patients. In this review, the function and regulation of cardiac PQC machinery in diabetes mellitus, and the therapeutic potential for the diabetic heart are discussed.

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Tanshinone IIA ameliorates diabetic cardiomyopathy by inhibiting Grp78 and CHOP expression in STZ‑induced diabetes rats

Cited by 17 publications

References 35 publications

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy

GAS5 regulates diabetic cardiomyopathy via miR‑221‑3p/p27 axis‑associated autophagy

Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside

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