Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis

Zhu, Kaiyi; Guo, Jia; Yu, Xiaoxue; Wang, Que; Yan, Chao; Qiu, Quan; Tang, Weiqing; Huang, Xiuqing; Mu, Hongna; Dou, Lin; Bian, Yunfei; Han, Qinghua; Shen, Tao; Li, Jian

doi:10.1155/2021/1815098

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…To further investigate our observations from studies in WT and Ad‐KO mice, we also used the cellular models of primary adult rat cardiomyocytes or H9c2 cells subjected to hypoxia. Previous studies have indicated that adiponectin reduced apoptosis induced by chronic intermittent hypoxia and inhibited hypoxia/reoxygenation‐induced necroptosis and intrinsic apoptosis via AdipoR1‐APPL1‐AMPK signaling in H9c2 cells 47,48 . We found that autophagy flux was enhanced following adiponectin treatment in normoxic or hypoxic conditions.…”

Section: Discussionmentioning

confidence: 50%

“…hypoxia inhibited hypoxia/reoxygenation-induced necroptosis and intrinsic apoptosis via APPL1-AMPK signaling in H9c2 cells. 47,48 We found that autophagy flux was enhanced following adiponectin treatment in normoxic or hypoxic conditions. Importantly, to verify the functional significance of adiponectin-stimulated autophagy, we generated an autophagy-deficient cell model using CRISPR to delete Atg7.…”

Section: Discussionmentioning

confidence: 87%

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Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux

Sung,

Tang,

Jahng

et al. 2024

Clinical Translational Sci

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Strategies to enhance autophagy flux have been suggested to improve outcomes in cardiac ischemic models. We explored the role of adiponectin in mediating cardiac autophagy under ischemic conditions induced by permanent coronary artery ligation. We studied the molecular mechanisms underlying adiponectin's cardio‐protective effects in adiponectin knockout (Ad‐KO) compared with wild‐type (WT) mice subjected to ischemia by coronary artery ligation and H9c2 cardiomyocyte cell line exposed to hypoxia. Systemic infusion of a cathepsin‐B activatable near‐infrared probe as a biomarker for autophagy and detection via noninvasive three‐dimensional fluorescence molecular tomography combined with computerized tomography to quantitate temporal changes, indicated increased activity in the myocardium of WT mice after myocardial infarction which was attenuated in Ad‐KO. Seven days of ischemia increased myocardial adiponectin accumulation and elevated ULK1/AMPK phosphorylation and autophagy assessed by Western blotting for LC3 and p62, an outcome not observed in Ad‐KO mice. Cell death, assessed by TUNEL analysis and the ratio of Bcl‐2:Bax, plus cardiac dysfunction, measured using echocardiography with strain analysis, were exacerbated in Ad‐KO mice. Using cellular models, we observed that adiponectin stimulated autophagy flux in isolated primary adult cardiomyocytes and increased basal and hypoxia‐induced autophagy in H9c2 cells. Real‐time temporal analysis of caspase‐3/7 activation and caspase‐3 Western blot indicated that adiponectin suppressed activation by hypoxia. Hypoxia‐induced mitochondrial reactive oxygen species production and cell death were also attenuated by adiponectin. Importantly, the ability of adiponectin to reduce caspase‐3/7 activation and cell death was not observed in autophagy‐deficient cells generated by CRISPR‐mediated deletion of Atg7. Collectively, our data indicate that adiponectin acts in an autophagy‐dependent manner to attenuate cardiomyocyte caspase‐3/7 activation and cell death in response to hypoxia in vitro and ischemia in mice.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 87%

Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux

Sung,

Tang,

Jahng

et al. 2024

Clinical Translational Sci

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“…Even though the causal relationship between necroptosis and inflammation is more complicated, the peaked expression of TNF-α and necroptotic proteins occurred simultaneously on day 14 after AD, suggesting that TNF-α might be an important trigger of AD necroptosis. The MAPK pathway, the downstream activation of oxidative stress, activated the inflammatory factor TNF-α, which is a key controller in the process of necroptosis via the modification of RIP1 and RIP3 ( 8 , 56 – 59 ). Herein, EGCG-NPs significantly decreased the expression of ERK1/2 and p-p38 in the epidermis, indicating that EGCG-NPs regulated necroptosis after AD by oxidative stress/MAPK/inflammation pathway.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative effects of epigallocatechin-3-gallate nanoparticles on 2,4-dinitrochlorobenzene induced atopic dermatitis: A potential mechanism of inflammation-related necroptosis

Han

Wang

et al. 2022

Front. Nutr.

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Atopic dermatitis (AD) is a common autoimmune and chronic inflammatory cutaneous disease with a relapsing-remitting course. Necroptosis is a regulated necrotic cell death mediated by receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed lineage kinase domain-like pseudokinase (MLKL), which is activated by tumor necrosis factor-α (TNF-α). However, the mechanism and the role of necroptosis have not been delineated in AD progression. (-)-Epigallocatechin-3-gallate (EGCG), the main biological activity of tea catechin, is well known for its beneficial effects in the treatment of skin diseases. Here, PEG-PLGA-EGCG nanoparticles (EGCG-NPs) were formulated to investigate the bioavailability of EGCG to rescue cellular injury following the inhibition of necroptosis after AD. 2,4-dinitrochlorobenzene (DNCB) was used to establish AD mouse models. As expected, topically applied EGCG-NPs elicited a significant amelioration of AD symptoms in skin lesions, including reductions in the ear and skin thickness, dermatitis score, and scratching behavior, which was accompanied by redox homeostasis restored early in the experiment. In addition, EGCG-NPs significantly decreased the expression of inflammatory cytokines like TNF-α, interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-17A (IL-17A) in a time-dependent manner than those of in AD group. As a result, the overexpression of RIP1, RIP3, and MLKL in the entire epidermis layers was dramatically blocked by EGCG-NPs, as well as the expression ofphosphorylated p38 (p-p38), extracellular signal-regulated kinase 1 (ERK1), and extracellular signal-regulated kinase 2 (ERK2). These findings promote that EGCG-NPs formulation represents a promising drug-delivery strategy for the treatment of AD by maintaining the balance of Th1/Th2 inflammation response and targeting necroptosis.

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“…Adiponectin (APN) is a fat factor secreted by the adipose tissue, which contributes to maintaining cardiovascular health [70]. APN has been reported to improve cardiomyopathy [71,72]. Further analysis showed that H 2 S therapy restored HFDinhibited APN levels and suppressed HG-induced cardiac ER stress.…”

Section: Hydrogen Sulfide Improves Diabetic Cardiomyopathy By Regulat...mentioning

confidence: 99%

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases

Zhao

Liu

Yang

et al. 2022

IJMS

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Endoplasmic reticulum (ER) plays important roles in protein synthesis, protein folding and modification, lipid biosynthesis, calcium storage, and detoxification. ER homeostasis is destroyed by physiological and pharmacological stressors, resulting in the accumulation of misfolded proteins, which causes ER stress. More and more studies have shown that ER stress contributes to the pathogenesis of many diseases, such as diabetes, inflammation, neurodegenerative diseases, cancer, and autoimmune diseases. As a toxic gas, H2S has, in recent years, been considered the third most important gas signal molecule after NO and CO. H2S has been found to have many important physiological functions and to play an important role in many pathological and physiological processes. Recent evidence shows that H2S improves the body’s defenses to many diseases, including diabetes, by regulating ER stress, but its mechanism has not yet been fully understood. We therefore reviewed recent studies of the role of H2S in improving diabetes-related diseases by regulating ER stress and carefully analyzed its mechanism in order to provide a theoretical reference for future research.

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Polypeptide Globular Adiponectin Ameliorates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Inhibiting Both Apoptosis and Necroptosis

Cited by 9 publications

References 36 publications

Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux

Ischemia‐induced cardiac dysfunction is exacerbated in adiponectin‐knockout mice due to impaired autophagy flux

Ameliorative effects of epigallocatechin-3-gallate nanoparticles on 2,4-dinitrochlorobenzene induced atopic dermatitis: A potential mechanism of inflammation-related necroptosis

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases

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