Effects of short‐chain acyl‐CoA dehydrogenase on cardiomyocyte apoptosis

Zeng, Zhenhua; Huang, Qiuju; Shu, Zhaohui; Liu, Peiqing; Pan, Xuediao; Zang, Lei; Zhou, Sigui

doi:10.1111/jcmm.12828

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…It was reported that PPAR- α activation could decrease IR-induced liver, heart, and brain injury by suppressing inflammation, apoptosis, and lipid peroxidation [ 41 , 42 ]. Furthermore, PPAR- α can promote the expression of Bcl-2 and subsequently inactivate apoptosis [ 43 ]. An experimental study suggested that fenofibrate could inhibit apoptosis through SIRT1-mediated deacetylation of FoxO1 [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

et al. 2021

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Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-α, which is associated with the phosphorylation of AMPK.

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Section: Discussionmentioning

confidence: 99%

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

et al. 2021

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“…Our previous study showed that SCAD expression was decreased in a cardiomyocyte apoptotic model [26]. Here, SCAD downregulation occurred in both tBHP-treated HUVECs and the human artery endothelial cell line HTX2397 apoptotic model and the oscillatory shear stress model, which imitated hypertensive stress.…”

Section: Discussionmentioning

confidence: 67%

Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling

Zhong¹,

Li²,

Xu³

et al. 2023

Journal of Hypertension

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Objectives:Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme in the fatty acid oxidation process, is not only involved in ATP synthesis but also regulates the production of mitochondrial reactive oxygen species (ROS) and nitric oxide synthesis. The purpose of this study was to investigate the possible role of SCAD in hypertension-associated vascular remodelling.Methods:In-vivo experiments were performed on spontaneously hypertensive rats (SHRs, ages of 4 weeks to 20 months) and SCAD knockout mice. The aorta sections of hypertensive patients were used for measurement of SCAD expression. In-vitro experiments with t-butylhydroperoxide (tBHP), SCAD siRNA, adenovirus-SCAD (MOI 90) or shear stress (4, 15 dynes/cm2) were performed using human umbilical vein endothelial cells (HUVECs).Results:Compared with age-matched Wistar rats, aortic SCAD expression decreased gradually in SHRs with age. In addition, aerobic exercise training for 8 weeks could significantly increase SCAD expression and enzyme activity in the aortas of SHRs while decreasing vascular remodelling in SHRs. SCAD knockout mice also exhibited aggravated vascular remodelling and cardiovascular dysfunction. Likewise, SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and the aortas of hypertensive patients. SCAD siRNA caused HUVEC apoptosis in vitro, whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Furthermore, SCAD expression was decreased in HUVECs exposed to low shear stress (4 dynes/cm2) and increased in HUVECs exposed to 15 dynes/cm2 compared with those under static conditions.Conclusion:SCAD is a negative regulator of vascular remodelling and may represent a novel therapeutic target for vascular remodelling.

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“…Transfection Reagent (Beyotime Biotechnology, Co., Ltd, Shanghai, China) according to the manufacturer's instructions, cultured in normal Dulbecco's modified Eagle's medium (DMEM) and then treated with riboflavin and tBHP. The SCAD and DJ-1 oligonucleotide duplex sequences were separately based on previous studies (W. Li, Li, Leng, et al, 2020;Zeng et al, 2016).…”

Section: Scad and Dj-1 Knockdown By Small-interfering Rna (Sirna)mentioning

confidence: 99%

“…For the first time, our previous studies found that SCAD expression was decreased in pathological cardiac hypertrophy, heart failure and cardiomyocyte apoptosis. SCAD is a negative regulatory factor of heart failure (J. Huang, Xu, et al, 2015; Q. Huang, Huang, et al, 2015; Zeng et al, 2016). Interestingly, mitochondrial proteome analysis showed that DJ‐1 was down‐regulated in SCAD deficiency patients (Pedersen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Riboflavin protects against heart failure via SCAD‐dependent DJ‐1–Keap1–Nrf2 signalling pathway

Cao

Zhong

et al. 2023

British J Pharmacology

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Background and PurposeOur recent studies have shown that flavin adenine dinucleotide (FAD) exerts cardiovascular protective effects by supplementing short‐chain acyl‐CoA dehydrogenase (SCAD). The current study aimed to elucidate whether riboflavin (the precursor of FAD) could improve heart failure via activating SCAD and the DJ‐1–Keap1–Nrf2 signalling pathway.Experimental ApproachRiboflavin treatment was given to the mouse transverse aortic constriction (TAC)‐induced heart failure model. Cardiac structure and function, energy metabolism and apoptosis index were assessed, and relevant signalling proteins were analysed. The mechanisms underlying the cardioprotection by riboflavin were analysed in the cell apoptosis model induced by tert‐butyl hydroperoxide (tBHP).Key ResultsIn vivo, riboflavin ameliorated myocardial fibrosis and energy metabolism, improved cardiac dysfunction and inhibited oxidative stress and cardiomyocyte apoptosis in TAC‐induced heart failure. In vitro, riboflavin ameliorated cell apoptosis in H9C2 cardiomyocytes by decreasing reactive oxygen species (ROS). At the molecular level, riboflavin significantly restored FAD content, SCAD expression and enzymatic activity, activated DJ‐1 and inhibited the Keap1–Nrf2/HO1 signalling pathway in vivo and in vitro. SCAD knockdown exaggerated the tBHP‐induced DJ‐1 decrease and Keap1–Nrf2/HO1 signalling pathway activation in H9C2 cardiomyocytes. The knockdown of SCAD abolished the anti‐apoptotic effects of riboflavin on H9C2 cardiomyocytes. DJ‐1 knockdown hindered SCAD overexpression anti‐apoptotic effects and regulation on Keap1–Nrf2/HO1 signalling pathway in H9C2 cardiomyocytes.Conclusions and ImplicationsRiboflavin exerts cardioprotective effects on heart failure by improving oxidative stress and cardiomyocyte apoptosis via FAD to stimulate SCAD and then activates the DJ‐1–Keap1–Nrf2 signalling pathway.

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Effects of short‐chain acyl‐CoA dehydrogenase on cardiomyocyte apoptosis

Cited by 13 publications

References 33 publications

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation

Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling

Riboflavin protects against heart failure via SCAD‐dependent DJ‐1–Keap1–Nrf2 signalling pathway

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