Perilipin 5 ameliorates high-glucose-induced podocyte injury via Akt/GSK-3β/Nrf2-mediated suppression of apoptosis, oxidative stress, and inflammation

Feng, Jie; Xie, Liyi; Yu, Xiaoyang; Liu, Chao; Dong, Hongjuan; Lu, Wei; Kong, Ranran

doi:10.1016/j.bbrc.2021.01.069

Cited by 19 publications

(12 citation statements)

References 41 publications

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“…Nrf2 signaling protects podocytes from HG injury. [41][42][43] Intriguingly, USP15 has been shown to play a vital role in regulating Nrf2 activation. 36 USP15 enhances the stability and enzymatic activity of the Keap1-Cul3-E3 ligase complex and thereby accelerates the degradation of Nrf2.…”

Section: Discussionmentioning

confidence: 99%

Inhibition ofUSP15ameliorates high‐glucose‐induced oxidative stress and inflammatory injury in podocytes through regulation of theKeap1/Nrf2signaling

Chen

et al. 2021

Environmental Toxicology

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Ubiquitin-specific peptidase 15 (USP15) is implicated in the pathogenesis of numerous diseases. However, whether USP15 plays a role in diabetic nephropathy remains undetermined. This project was designed to determine the potential role of USP15 in mediating high glucose (HG)-induced podocyte injury, a key event in the pathogenesis of diabetic nephropathy. We found that USP15 levels were elevated in podocytes after HG stimulation. Inhibition of USP15 led to decreases in HG-evoked apoptosis, oxidative stress, and inflammation in podocytes. Further investigation showed that inhibition of USP15 enhanced the activation of NF-E2-related factor 2 (Nrf2) and expression of Nrf2 target genes in HG-simulated podocytes. Moreover, depletion of Kelch-like ECH-associated protein 1 (Keap1) diminished the regulatory effect of USP15 inhibition on Nrf2 activation. In addition, Nrf2 suppression reversed USP15-inhibition-induced protective effects in HG-injured podocytes. Taken together, these data indicate that USP15 inhibition protects podocytes from HGinduced injury by enhancing Nrf2 activation via Keap1.

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Section: Discussionmentioning

confidence: 99%

Inhibition ofUSP15ameliorates high‐glucose‐induced oxidative stress and inflammatory injury in podocytes through regulation of theKeap1/Nrf2signaling

Chen

et al. 2021

Environmental Toxicology

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“…8 In addition, Perilipin 5 also prevents apoptosis, oxidative stress and inflammation induced by high sugar in podocytes through this pathway. 9 In the current report, AS-IV has been reported to inhibit the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Akt/GSK3β signaling pathway. 10 However, whether the mechanism of AS-IV treatment of diabetes involves the Akt/GSK3β/Nrf2 Pathway is still unknown.…”

Section: Introductionmentioning

confidence: 78%

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

Lin¹,

Xu²,

Zheng³

et al. 2022

DMSO

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Background: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and antiapoptotic properties, and exerts anti-diabetic pharmacological effects. Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism. Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated. Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and upregulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZinduced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells. Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.

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“…Research shows that Plin5 ameliorates podocyte injury induced by high glucose by inhibiting Akt/GSK-3BETA/NRF2-mediated apoptotic oxidative stress and inflammation [ 252 ]. The result suggests that intervention of Plin5-related inflammatory and oxidative stress pathway may also reduce DC.…”

Section: Clinical Interventionmentioning

confidence: 99%

Plin5, a New Target in Diabetic Cardiomyopathy

Cui

Wang

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.

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Perilipin 5 ameliorates high-glucose-induced podocyte injury via Akt/GSK-3β/Nrf2-mediated suppression of apoptosis, oxidative stress, and inflammation

Cited by 19 publications

References 41 publications

Inhibition ofUSP15ameliorates high‐glucose‐induced oxidative stress and inflammatory injury in podocytes through regulation of theKeap1/Nrf2signaling

Inhibition ofUSP15ameliorates high‐glucose‐induced oxidative stress and inflammatory injury in podocytes through regulation of theKeap1/Nrf2signaling

Astragaloside IV Ameliorates Streptozotocin Induced Pancreatic β-Cell Apoptosis and Dysfunction Through SIRT1/P53 and Akt/GSK3β/Nrf2 Signaling Pathways

Plin5, a New Target in Diabetic Cardiomyopathy

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