Impaired Protein Quality Control During Left Ventricular Remodeling in Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor

Hartupee, Justin; Szalai, Gabor; Wang, Wei; Ma, Xiucui; Diwan, Abhinav; Mann, Douglas L.

doi:10.1161/circheartfailure.117.004252

Cited by 15 publications

(10 citation statements)

References 42 publications

(56 reference statements)

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“…During autophagy, an isolation membrane sequesters long-lived proteins and organelles that are damaged or malfunctioning to form the autophagosome, then the autophagosome fuses with the lysosome to become an autolysosome and degrades the materials contained within it. Dysregulated autophagy can cause various cardiovascular diseases including hypertrophy, heart failure and ischemic heart diseases [2]. Recently, it has been reported that autophagy inhibition or autophagy flux impairment can cause cardiac hypertrophy [3][4][5][6].…”

Section: Ivyspringmentioning

confidence: 99%

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Wang¹,

Xi²,

Hu³

et al. 2020

Int. J. Biol. Sci.

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Nicotine is proved to be an important factor for cardiac hypertrophy. Autophagy is important cell recycling system involved in the regulation of cardiac hypertrophy. Cilostazol, which is often used in the management of peripheral vascular disease. However, the effects of cilostazol on nicotine induced autophagy and cardiac hypertrophy are unclear. Here, we aim to determine the role and molecular mechanism of cilostazol in alleviating nicotine-induced cardiomyocytes hypertrophy through modulating autophagy and the underlying mechanisms. Our results clarified that nicotine stimulation caused cardiomyocytes hypertrophy and autophagy flux impairment significantly in neonatal rat ventricular myocytes (NRVMs), which were evidenced by augments of LC3-II and p62 levels, and impaired autophagosomes clearance. Interestingly, cathepsin B (CTSB) activity decreased dramatically after stimulation with nicotine in NRVMs, which was crucial for substrate degradation in the late stage of autophagy process, and cilostazol could reverse this effect dramatically. Intracellular ROS levels were increased significantly after nicotine exposure. Meanwhile, p38MAPK and JNK were activated after nicotine treatment. By using ROS scavenger N-acetyl-cysteine (NAC) could reverse the effects of nicotine by down-regulation the phosphorylation of p38MAPK and JNK pathways, and pretreatment of specific inhibitors of p38MAPK and JNK could restore the autophagy impairment and cardiomyocytes hypertrophy induced by nicotine. Moreover, CTSB activity of lysosome regained after the treatment with cilostazol. Cilostazol also inhibited the ROS accumulation and the activation of p38MAPK and JNK, which providing novel connection between lysosome CTSB and ROS/p38MAPK/JNK related oxidative stress pathway. This is the first demonstration that cilostazol could alleviate nicotine induced cardiomyocytes hypertrophy through restoration of autophagy flux by activation of CTSB and inhibiting ROS/p38/JNK pathway, exhibiting a feedback loop on regulation of autophagy and cardiomyocytes hypertrophy.

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Section: Ivyspringmentioning

confidence: 99%

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Wang¹,

Xi²,

Hu³

et al. 2020

Int. J. Biol. Sci.

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“…mTOR can be activated by the PI3K/PDK/Akt pathway. Chronic upregulation of mTORC1 is associated with increased cardiac hypertrophy (both physiologic and pathologic) ( 84 , 85 ). Data from human subjects as well as animal studies show that decreased oxygen in the heart increases glutamine uptake and alanine release into the blood ( 86 , 87 ).…”

Section: Biosynthesis and Turnover Of Macromoleculesmentioning

confidence: 99%

Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

Karlstaedt

Schiffer

Taegtmeyer

2018

Front. Cardiovasc. Med.

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Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

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“…Another class of cytokines, the tumor necrosis factor (TNF), is a ubiquitous cell signaling protein produced by various cells. Sustained in ammatory signaling by cardiac overexpression of TNF-α leads to proteotoxicity and cell death in the heart (27). In the present study, the high expression of IL-1β, IL-6 and TNF-α in the myocardium may aggravate myocardial damage.…”

Section: Discussionmentioning

confidence: 56%

Protective effects of ginsenoside Rc against acute cold exposure‐induced myocardial injury in rats

Xue

Zhang

et al. 2021

Journal of Food Science

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Background: Ginsenoside Rc is one of the cardinal bioactive components of Panax ginseng that has been studied for various biological activities. This study aimed to investigate the protective effects of ginsenoside Rc against acute cold exposure induced myocardial injury in rats.Methods: The rats were intragastrically administrated with ginsenoside Rc (10, 20 mg/kg) or vehicle daily for 7 days. One hour after the seventh-day administration, 3% pentobarbital sodium was used to anesthetize the rats. Rats of the control group were kept in room temperature (22 ± 1 ℃) and the other groups of rats were exposed to low ambient temperature (-15 ± 1 ℃) in a cold chamber for 6 h. Cardiac function was monitored and recorded as well. To evaluate the protective effects of ginsenoside Rc, we also measured myocardial speci c enzymes (lactate dehydrogenase, aspartate aminotransferase and creatine kinase-MB) in plasma, whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and hematocrit (HCT). The pathological changes of myocardium were observed through histopathological examination. The mRNA expression levels of TNF-α, IL-1β and IL-6 were by real-time quantitative PCR analysis. And the expressions of silent information regulator1 (SIRT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax) and Procaspase-3 in heart tissues were measured by Western blot method.Results: Ginsenoside Rc alone had no effect on cardiac function, myocardial enzyme activities and hemorheology in normal rats. Compared with the model group, pretreatment with ginsenoside Rc signi cantly improved cardiac function, diminished myocardial speci c enzymes release and decreased erythrocyte aggregation index. As a result, the pretreatment regulated abnormal hemorheology, attenuated myocardial histological changes and structural abnormalities, reduced the mRNA expression levels of cardiac in ammatory markers. Ginsenoside Rc also resulted in up-regulating SIRT1, Bcl-2 and Procaspase-3 expressions and down-regulating Bax expression. Conclusion:The current study suggests that ginsenoside Rc alleviates acute cold exposure induced myocardial injury in rats by inhibiting cardiomyocyte apoptosis via SIRT1 and reducing in ammatory response.Panax ginseng C. A. Meyer (P. ginseng) is an herbal plant that has been used as a traditional medicine in Asian countries for thousands of years. Ginsenosides are the principle active constituent found in P. ginseng and exhibit anti-oxidative, anti-in ammatory and anti-cancer activities (5-7). Ginsenoside Rc is one of protopanaxadiol type ginsenosides that has been studied for various biological activities (8-10) (Fig. 1). It is reported that ginsenoside Rc can suppress oxidative stress by in uencing FoxO1 activity via Akt pathway in human embryo kidney 293T cells (10).The mammalian sirtuins are a highly conserved family of NAD + -dependent enzymes that regulate cellular stress resistance, energy metabolism, genomic stability and tumorigenesis (11). Silent information regulator 1 (SIRT1) is one of the s...

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Impaired Protein Quality Control During Left Ventricular Remodeling in Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor

Cited by 15 publications

References 42 publications

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Cilostazol alleviate nicotine induced cardiomyocytes hypertrophy through modulation of autophagy by CTSB/ROS/p38MAPK/JNK feedback loop

Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

Protective effects of ginsenoside Rc against acute cold exposure‐induced myocardial injury in rats

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