Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling

2020 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Mitochondrial Membrane ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Salvia Miltiorrhiza Bunge ◽  
Pharmacological Activities ◽  
Heavy Burden ◽  
Induced Apoptosis

Abstract Background: Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action.Results: We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion: TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

scholarly journals Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signaling

2020 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Mitochondrial Membrane ◽  
Salvia Miltiorrhiza ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Salvia Miltiorrhiza Bunge ◽  
Pharmacological Activities ◽  
Heavy Burden ◽  
Induced Apoptosis

Abstract Background: Acute myocardial infarction (AMI) is the leading cause of death globally and has thus placed a heavy burden on healthcare. Tanshinone IIA (TSA) is a major active compound, extracted from Salvia miltiorrhiza Bunge, that possesses various pharmacological activities. The aim of the present study was to investigate the role of TSA in AMI and its underlying mechanism of action.Results: We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion: TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

scholarly journals Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocytes injury via lncRNA AK003290/miR-124-5p signaling

2019 ◽  
Author(s):  
Liye Chen ◽  
Lili Wei ◽  
Qiongyang Yu ◽  
Haozhe Shi ◽  
George Liu
Keyword(s):  
Salvia Miltiorrhiza ◽  
Annexin V ◽  
Protective Role ◽  
Tanshinone Iia ◽  
Activity Assay ◽  
Western Blot Assay ◽  
Expression Of Genes ◽  
Commercial Kits ◽  
Induced Apoptosis

Abstract Objective Acute myocardial infarction (AMI) is the leading cause of death and one of the heaviest healthy burden globally nowadays. Tanshinone IIA (TSA) is the major active compound extracted form Salvia miltiorrhiza Bunge possessing various of pharmacology activities. The present study aimed at investigating the role of TSA in AMI and underlying mechsniam.Methods Quantitative real-time PCR (qRT-PCR) and western blot assay were performed to detect the expression of genes and proteins. Cell apoptosis was detected by Annexin/V PI staining and flow cytometry. The amount of LDH, MDA and ROS were detected using commercial kits. FISH experiment was used to detect the expression of AK003290 in cardiomyocytes. Luciferace activity assay was performed to verify the interaction between AK003290 and miR-124-5p.Results We have shown that TSA decreased the apoptosis rate, the amount of LDH, MDA as well as ROS of cardiomyocytes. Meantime, it elevated mitochondrial membrane potential (MMP) which was decreased by H/R treatment. It was also determined that miR-124-5p targets AK003290 directly. TSA up-regulated the expression of AK003290 and its function can be reversed by knock down of AK003290 as well as miR-124-5p overexpression.Conclusion TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

scholarly journals MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction

2017 ◽  
Vol 312 (4) ◽  
pp. F589-F598 ◽  
Author(s):  
Yan Guo ◽  
Xu Deng ◽  
Shuang Chen ◽  
Lingyun Yang ◽  
Jiajia Ni ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Early Event ◽  
Dependent Manner ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Adenovirus E1b ◽  
Induced Apoptosis

MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L.

Reactive oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury

2016 ◽  
Vol 310 (7) ◽  
pp. F669-F678 ◽  
Author(s):  
Mi Bai ◽  
Ruochen Che ◽  
Yue Zhang ◽  
Yanggang Yuan ◽  
Chunhua Zhu ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Annexin V ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ros Generation ◽  
Dependent Manner ◽  
Related Gene ◽  
Podocyte Injury ◽  
Induced Apoptosis

Evidence has demonstrated that aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases. The purpose of the present study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine and N-acetylcysteine. Cell apoptosis was investigated by detecting annexin V conjugates, apoptotic bodies, caspase-3 activity, and alterations of the podocyte protein nephrin. Autophagy was evaluated by measuring the expressions of light chain 3, p62, beclin-1, and autophagy-related gene 5. Aldo (10−7 mol/l) induced podocyte apoptosis, autophagy, and downregulation of nephrin protein in a time-dependent manner. Aldo-induced apoptosis was further promoted by the inhibition of autophagy via 3-methyladenine and autophagy-related gene 5 small interfering RNA pretreatment. Moreover, Aldo time dependently increased ROS generation, and H2O2 (10−4 mol/l) application remarkably elevated podocyte autophagy. After treatment with N-acetylcysteine, the autophagy induced by Aldo or H2O2 was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of ROS could also lessen Aldo-induced podocyte injury. Taken together, our findings suggest that ROS-triggered autophagy played a protective role against Aldo-induced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy.

Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3

2021 ◽  
Author(s):  
Fengyun Zhou ◽  
Ting Feng ◽  
Xiangqi Lu ◽  
Huicheng Wang ◽  
Yangping Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cytochrome C Release ◽  
Neonatal Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

scholarly journals Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

2018 ◽  
Author(s):  
Shuang Nie ◽  
Yaqing Huang ◽  
Mengyue Shi ◽  
Xuetian Qian ◽  
Hongzhen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Underlying Mechanism ◽  
Protective Role

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

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