Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets

Zheng, Pengfei; Xie, Zhonglin; Yuan, Yuan; Sui, Wen; Wang, Chao; Gao, Xing; Zhao, Yuliang; Zhang, Feng; Gu, Yu; Hu, Peizhen; Ye, Jing; Feng, Xing; Zhang, Lijun

doi:10.1038/srep42574

Cited by 65 publications

(75 citation statements)

References 32 publications

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“…The inconformity in changes of cardiac function may be due to differences in the severity of cardiac microvascular and myocardial damage. Consistent with our data, other studies have shown that Plin5 knockout is considered to have no effect on cardiac function in the physiological state [31,66], but aggravate cardiac dysfunction induced by old age or ischemic stimuli in mice [14]. Furthermore, we found that Plin5 deficiency increased apoptosis rate and decreased NO synthesis in CMECs under the condition of HG-HFFAs.…”

Section: Discussionsupporting

confidence: 92%

“…In line with our studies, many previous studies claimed that Plin5 knockout was able to increase the level of FFAs, enhance the β-oxidation of FFAs, and ultimately increase the production of ROS [14,31]. In myocardial ischemia-reperfusion injury, it has been reported that Plin5 ablation can increase the content of ROS and malondialdehyde (MDA), but reduce the level of superoxide dismutase (SOD) [31]. Therefore, these results suggest that ROS overload derived from FFAs β-oxidation contributes to CMECs injury induced by the disruption of Plin5 balance in T2DM-HFFA.…”

supporting

confidence: 91%

“…Moreover, NAC intervention reduced the content of ROS, partly reversed the CMECs injury induced by the deletion and phosphorylation of Plin5. In line with our studies, many previous studies claimed that Plin5 knockout was able to increase the level of FFAs, enhance the β-oxidation of FFAs, and ultimately increase the production of ROS [14,31]. In myocardial ischemia-reperfusion injury, it has been reported that Plin5 ablation can increase the content of ROS and malondialdehyde (MDA), but reduce the level of superoxide dismutase (SOD) [31].…”

supporting

confidence: 89%

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Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism Bidirectionally

Hou

Feng

et al. 2019

SSRN Journal

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Background. Hyper-free fatty acidemia (HFFA) impairs cardiac capillaries, as well as type 2 diabetes mellitus (T2DM). Perilipin 5 (Plin5) maintains metabolic balance of free fatty acids (FFAs) in high oxidative tissues via the states of nonphosphorylation and phosphorylation. However, when facing to T2DM-HFFA, Plin5's role in cardiac microvascular endothelial cells (CMECs) is not defined. Methods. In mice of WT or Plin5 -/-, T2DM models were rendered by high-fat diet combined with intraperitoneal injection of streptozocin. CMECs isolated from left ventricles were incubated with high glucose (HG) and high FFAs (HFFAs). Plin5 phosphorylation was stimulated by isoproterenol. Plin5 expression was knocked down by small interfering RNA (siRNA). We determined cardiac function by small animal ultrasound, apoptotic rate by flow cytometry, microvessel quantity by immunohistochemistry, microvascular integrity by scanning electron microscopy, intracellular FFAs by spectrophotometry, lipid droplets (LDs) by Nile red staining, mRNAs by quantitative real-time polymerase chain reaction, proteins by western blots, nitric oxide (NO) and reactive oxygen species (ROS) by fluorescent dye staining and enzyme-linked immunosorbent assay kits. Results. In CMECs, HFFAs aggravated cell injury induced by HG and activated Plin5 expression. In mice with T2DM-HFFA, Plin5 deficiency reduced number of cardiac capillaries, worsened structural incompleteness, and enhanced diastolic dysfunction. Moreover, in CMECs treated with HG-HFFAs, both ablation and phosphorylation of Plin5 reduced LDs content, increased intracellular FFAs, stimulated mitochondrial β-oxidation, added ROS generation, and reduced the expression and activity of endothelial nitric oxide synthase (eNOS), eventually leading to increased apoptotic rate and decreased NO content, all of which were reversed by N-acetyl-L-cysteine. Conclusion. Plin5 preserves lipid balance and cell survival in diabetic CMECs by regulating FFAs metabolism bidirectionally via the states of nonphosphorylation and phosphorylation.

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Section: Discussionsupporting

confidence: 92%

supporting

confidence: 91%

supporting

confidence: 89%

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Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism Bidirectionally

Hou

Feng

et al. 2019

SSRN Journal

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“…Zheng et al studied myocardium from PLIN5-deicient mice and found that the ROS production and malondialdehyde levels, a marker for oxidative stress, were signiicantly increased [96]. In this model, the phosphorylation of PI3K and Akt, which was induced by ischemia/reperfusion injury, was greatly reduced by PLIN5 deletion in the myocardium.…”

Section: Oxidative Stress Theorymentioning

confidence: 99%

Role of Lipid Droplet Proteins in the Development of NAFLD and Hepatic Insulin Resistance

Minehira¹,

Gual²

2018

Non-Alcoholic Fatty Liver Disease - Molecular Bases, Prevention and Treatment

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NAFLD is diagnosed, when the liver fat exceeds more than 5% of liver weight. Inside of hepatocytes, these fats are stored in cytosolic lipid droplets. The lipid droplets can be formed from a bud, vesicles of the lipid bilayer, which lines at a vicinity of the endoplasmic reticulum (ER). On the surface of droplets, there are several structural/ functional proteins such as lipid droplet proteins, lipogenic enzymes, and lipases. Interestingly, the lipid droplet proteins seem to have great impact on a development of NAFLD. Some proteins can interact with transcriptional factors such as SREBP1c and PPAR-alpha/gamma, and some proteins strongly impact a mitochondrial structure. As a result, the lipid droplet proteins highly inluence lipid handling and faty acid oxidation in hepatocytes. This chapter will elucidate our recent understanding of the role of each lipid droplet protein in faty liver formation and in hepatic insulin resistance. Existing information on genetically modiied animals as well as on human NAFLD was reviewed on Perilipin families, CIDE proteins, Seipin, and PNPLAs. Finally, the chapter will discuss how the lipid droplet proteins could potentially lead/protect from hepatic insulin resistance via abnormal accumulation of ceramides and diacylglycerols, autophagy, ER stress, and oxidative stress.

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“…Among these, Perilipin 5 (Plin5) is mainly expressed in tissues with very active lipid catabolism, including heart, brown adipose tissue, skeletal muscle, and liver and promotes LD accumulation but inhibits lipolysis by interacting with lipases such as ATGL, Abhd5 and CGI-58 (16)(17)(18)(19)(20). By modulating lipid homeostasis, Plin5 plays a role in ameliorating oxidative stress-induced damage in heart, skeletal muscle, hepatic stellate cells and aortic valve tissues (21)(22)(23)(24)(25). However, the regulation of Plin5 in FFA-induced oxidative stress and oxidant damage in pancreatic β-cells, to our knowledge, is not established until now.…”

Section: Introductionmentioning

confidence: 99%

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

et al. 2020

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Oxidative stress induced by free fatty acid overload in pancreatic β-cells is a potential contributory factor to dysfunction of insulin secretion and apoptotic cell death. Perilipin 5 (Plin5) has been reported to ameliorate oxidative stress-mediated damage in non-insulin-secreting tissues. We tested the hypothesis that Plin5 plays a similar role in pancreatic β-cells, which are extremely sensitive to oxidative stress. Here, our in vitro data showed that Plin5-mediated alleviation of palmitate-triggered apoptosis involves the mitochondrial pathway. And the protective role of Plin5 on β-cells was partially dependent on its modulation in oxidative stress. Upregulation of Plin5 in INS-1 cells decreased reactive oxygen species production, enhanced cellular glutathione levels, and induced expression of antioxidant enzymes glutamate-cysteine ligase catalytic subunit and heme oxygenase-1. However, knocking out of Plin5 abolished all of these beneficial effects. Furthermore, by using the O 2− scavenger MnTMPyP, we verified that altering Plin5 expression impacted lipotoxic cell death partially via modulating oxidative stress. Mechanistic experiments revealed that Plin5 induced Nrf2-ARE system, a master regulator in the cellular adaptive response to oxidative stress, by activating PI3K/Akt and ERK signal pathways, contributing to the increase of antioxidant defense and consequently improving β-cell function and survival in the presence of lipotoxic oxidative stress. Overall, our findings indicate that Plin5 abrogates oxidative damage in INS-1 β-cells during lipotoxic stress partially through the enhancement of antioxidant defense involving the PI3K/Akt and ERK mediated Nrf2-ARE system.

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Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets

Cited by 65 publications

References 32 publications

Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism Bidirectionally

Plin5/p-Plin5 Guards Diabetic CMECs by Regulating FFAs Metabolism Bidirectionally

Role of Lipid Droplet Proteins in the Development of NAFLD and Hepatic Insulin Resistance

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

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