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

2021 ◽  
Vol 544 ◽  
pp. 22-30
Author(s):  
Jie Feng ◽  
Liyi Xie ◽  
Xiaoyang Yu ◽  
Chao Liu ◽  
Hongjuan Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Podocyte Injury ◽  
Perilipin 5 ◽  
Gsk 3Β

scholarly journals Superoxide Destabilization of β-Catenin Augments Apoptosis of High-Glucose-Stressed Mesangial Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2934-2942 ◽  
Author(s):  
Chun-Liang Lin ◽  
Jeng-Yi Wang ◽  
Jih-Yang Ko ◽  
Kameswaran Surendran ◽  
Yu-Ting Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Renal Tissue ◽  
Dominant Negative ◽  
Gsk 3Β

Intense mesangial cell apoptosis contributes to the pathogenesis of diabetic nephropathy. Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/β-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/β-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3β) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. Inactivation of Ras and Racl also reversed Wnt/β-catenin expression and survival of mesangial cells. Stabilization of β-catenin by the transfection of stable β-catenin (Δ45) and kinase-inactive GSK-3β attenuated high-glucose-mediated mesangial cell apoptosis. Exogenous superoxide dismutase administration attenuated urinary protein secretion in diabetic rats and abrogated diabetes-mediated reactive oxygen radical synthesis in renal glomeruli. Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/β-catenin expression in renal glomeruli. Taken together, high glucose induced oxidative stress and apoptosis in mesangial cells. The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3β and inhibiting Wnt5a/β-catenin signaling. Controlling oxidative stress and Wnt/β-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose.

miR‐15b‐5p ameliorated high glucose‐induced podocyte injury through repressing apoptosis, oxidative stress, and inflammatory responses by targeting Sema3A

2019 ◽  
Vol 234 (11) ◽  
pp. 20869-20878 ◽  
Author(s):  
Yanqin Fu ◽  
Chongxian Wang ◽  
Dongming Zhang ◽  
Xiaojing Chu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Podocyte Injury

scholarly journals MiR-203-3p inhibits the oxidative stress, inflammatory responses and apoptosis of mice podocytes induced by high glucose through regulating Sema3A expression

2020 ◽  
Vol 15 (1) ◽  
pp. 939-950
Author(s):  
Jingfu Chen ◽  
Qing Xu ◽  
Wei Zhang ◽  
YuLan Zhen ◽  
Fei Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Renal Injury ◽  
Inflammatory Responses ◽  
Cell Model ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Podocyte Injury

AbstractDiabetic nephropathy (DN) is the most serious long-term microvascular complication of diabetes, which mainly causes podocyte injury. Many studies have shown that microRNAs play a vital role in the development of DN. Studies have shown that miR-203-3p is involved in mesangial cell proliferation and apoptosis of DN mice. Therefore, we speculated that miR-203-3p might be related to the development of DN, but our study does not provide any evidence. In animal experiments, diabetic mice (db/db) were transfected with iR-203-3p overexpression lentiviral vectors (LV-miR-203-3p) and their control (LV-miR-con), with normal mice (db/m) being used as the control. High glucose (HG)-induced podocytes were used to construct a DN cell model in vitro. The expression levels of miR-203-3p, Semaphorin 3A (Sema3A) and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction. Also, serum creatinine and blood urea nitrogen levels were used to evaluate the degree of renal injury in DN mice. Sema3A and apoptosis-related protein levels were assessed by the western blot analysis. Enzyme-linked immunosorbent assay was used to determine the different oxidative stress-related indicators and inflammatory cytokines. Flow cytometry and caspase-3 activity detection were used to analyze the degree of podocyte apoptosis. Our results suggested that the expression of miR-203-3p was lower in DN mice and in HG-induced podocytes. Overexpression of miR-203-3p reduced the body weight, blood glucose and renal injury of DN mice in vivo, as well as relieve the oxidative stress, inflammatory response and apoptosis of HG-induced podocytes in vitro. Functionally, Sema3A was a target of miR-203-3p, and Sema3A overexpression reversed the inhibitory effect of miR-203-3p on HG-induced podocyte injury. Our findings revealed that miR-203-3p alleviated the podocyte injury induced by HG via regulating Sema3A expression, suggesting that miR-203-3p might be a new therapeutic target to improve the progression of DN.

scholarly journals Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

2021 ◽  
Author(s):  
Zhao Chen ◽  
Lifang Tian ◽  
Li Wang ◽  
Xiaotao Ma ◽  
Fuqian Lei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
High Glucose ◽  
Glycogen Synthase ◽  
Related Factor ◽  
Protective Effects ◽  
Gsk 3Β ◽  
Induced Apoptosis

Abstract Hyperglycemia-induced oxidative stress of podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported as a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. The aims of this work were to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress and inflammatory response in podocytes in vitro. Herein, our results showed a marked increase in TRIM32 expression in HG-exposed podocytes. Loss-of-function experiments showed that the knockdown of TRIM32 improved the viability of HG-stimulated podocytes, and suppressed HG-induced apoptosis, oxidative stress and inflammatory response in podocytes. Further investigation revealed that the inhibition of TRIM32 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) axis in podocytes following HG exposure. However, the suppression of Akt abrogated the TRIM32-knockdown-mediated activation of Nrf2 in HG-exposed podocytes. In addition, the knockdown of Nrf2 markedly abolished the TRIM32-inhibition-induced protective effects in HG-exposed podocytes. In summary, the results of this work show that the inhibition of TRIM32 protects podocytes from HG-induced injury by potentiating Nrf2 signaling via the modulation of Akt/GSK-3β signaling. This study indicates a potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.

scholarly journals High glucose-induced ubiquitylation of G6PD leads to the injury of podocyte

2018 ◽  
Author(s):  
Meng Wang ◽  
Ji Hu ◽  
Linling Yan ◽  
Yeping Yang ◽  
Min He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
High Glucose ◽  
Mrna Level ◽  
Diabetic Patients ◽  
Podocyte Injury ◽  
Von Hippel Lindau ◽  
Ros Accumulation ◽  
Lysine Residues ◽  
Glucose 6 Phosphate Dehydrogenase

AbstractOxidative stress contributes substantially to podocyte injury in diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase is critical in maintaining NADPH, an important cofactor for antioxidant system. Here, we hypothesized that high glucose induces ubiquitylation and degradation of G6PD, which injures podocytes by reactive oxygen species (ROS) accumulation. We found that both G6PD protein expression and G6PD activity was decreased in kidneys of both diabetic patients and diabetic rodents. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD induced podocyte apoptosis. In G6PD deficient mice, podocyte apoptosis was also largely increased. High glucose had no effect on G6PD mRNA level but it caused decreased G6PD protein expression, which was mediated by the ubiquitin proteasome pathway. Furthermore, von Hippel−Lindau (VHL), an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on lysine residues 366/403. Our data suggest that high glucose induces ubiquitylation of G6PD by VHL, which leads to ROS accumulation and podocyte injury.

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