Up-regulating Lipin1 Attenuates High Glucose-Induced Apoptosis in RSC96 cells Through Regulating Mitochondrial Dynamics

2021 ◽  
Author(s):  
Wenjia SUN ◽  
Xianghua ZHUANG ◽  
Shuyan YU ◽  
Wei Liu ◽  
Min XU ◽  
...  
Keyword(s):  
Cell Viability ◽  
Schwann Cells ◽  
High Glucose ◽  
Mitochondrial Dynamics ◽  
Treatment Strategies ◽  
Public Health Problem ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Glucose Stimulation ◽  
Related Proteins

Abstract Diabetic peripheral neuropathy, one of the major complications resulting from diabetes, affects diabetic patients with high morbidity and mortality. It has emerged as a severe public health problem. However, its underlying pathogenesis and effective treatment strategies have not been fully studied. In the present study, we explored the role of lipin1 on mitochondrial function of Schwann cells under diabetic conditions. With high glucose stimulation or lipin1 down-regulation, the cell viability of Schwann cells was inhibited,accompanied with mitochondrial dysfunction and morphological abnormality. Besides, we found that high glucose stimulation or lipin1 silencing also disturbed the balance of mitochondrial dynamics, presented as increased levels of mitochondrial fission-related proteins (including DRP1 and FIS1) and decreased levels of mitochondrial fusion-related proteins (including MFN1 and OPA1). Furthermore, we demonstrated that up-regulating lipin1 ameliorated high glucose-induced disorder of mitochondrial dynamics and functions, and ultimately improved cell viability. Our results suggest that lipin1 may play a protective role on high glucose-stimulated Schwann cells through regulating the balance of mitochondrial dynamics.

scholarly journals NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaotian Zhang ◽  
Jiezhi Dai ◽  
Li Li ◽  
Hua Chen ◽  
Yimin Chai
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Chronic Wound ◽  
Diabetic Patients ◽  
Glucose Stimulation ◽  
M1 Macrophage ◽  
Novel Target ◽  
Diabetic Wounds ◽  
Nlrp3 Expression ◽  
Wound Tissue

Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1β expression. Results. The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P<0.05). High glucose induced a significant increase in NLRP3 inflammasome and IL-1β expression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1β. Conclusion. The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound.

miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling

2022 ◽  
pp. 1-13
Author(s):  
Hong Zheng ◽  
Jian Huang ◽  
Ming Zhang ◽  
Hu-Juan Zhao ◽  
Pang Chen ◽  
...  
Keyword(s):  
Cell Viability ◽  
High Glucose ◽  
Cell Damage ◽  
Malonic Dialdehyde ◽  
Spermatogenic Cell ◽  
Luciferase Reporter ◽  
Spermatogenic Cells ◽  
Testicular Damage ◽  
Hexosamine Biosynthetic Pathway ◽  
Related Proteins

<b><i>Introduction:</i></b> Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. <b><i>Methods:</i></b> GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. Cell apoptosis was determined using flow cytometry assay. Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). <b><i>Results:</i></b> miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. miR-27b-3p directly bound to Gfpt1 and negatively regulated its expression. <b><i>Conclusion:</i></b> miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage.

scholarly journals Aloperine attenuates high glucose-induced oxidative injury in Schwann cells via activation of NRF2/HO-1 pathway

2020 ◽  
Vol 19 (6) ◽  
pp. 1147-1152
Author(s):  
Yiran Chen ◽  
Tieming Ma ◽  
Zhimin Wang ◽  
Lianqun Jia ◽  
Xiaoqing Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Schwann Cells ◽  
High Glucose ◽  
Cell Injury ◽  
Annexin V ◽  
Oxidative Injury ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Oxygen Species ◽  
Potent Drug

Purpose: To determine the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the action of aloperine on Schwann cell injury caused by high glucose (HG).Methods: Cell viability was determined using MTT assay while the release of lactate dehydrogenase (LDH) was determined by biochemical assay. Apoptosis was assessed using flow cytometry, while the levels of malondialdehyde (MDA) were determined by Annexin V-FIT staining. Glutathione Stransferase (GST), glutathione peroxidase (GPX), and reactive oxygen species (ROS) were determined using enzyme-linked immunosorbent assay.Results: Treatment with HG suppressed RSC96 cell viability and increased LDH release, while aloperine reversed these results (p < 0.05). Apoptosis of RSC96 cells was induced by HG stimulation, but was abolished by aloperine. The levels of ROS, MDA, and GST were enhanced in cells followingtreatment with HG, but was reversed by aloperine (p < 0.05). The decreased level of GPX caused by HG in RSC96 cells was elevated by aloperine. Moreover, aloperine upregulated NRF2 and HO-1 in RSC96 cells treated with HG (p < 0.05).Conclusion: Aloperine attenuates HG-induced oxidative injury in Schwann cells via activation of NRF2/HO-1 pathway, suggesting its potential as a potent drug for the management of diabetic peripheral neuropathy. Keywords: Aloperine, Schwann cells, High glucose, Oxidative stress, NRF2, HO-1

scholarly journals Deteksi Dini Penyakit Arteri Perifer pada Pasien Diabetes Melitus di Kota Mataram

2020 ◽  
Vol 2 (3) ◽  
pp. 256-262
Author(s):  
Yanna Indrayana ◽  
Herpan Syafii Harahap ◽  
Ilsa Hunaifi
Keyword(s):  
Diabetes Mellitus ◽  
Early Detection ◽  
Peripheral Artery Disease ◽  
Blood Glucose Control ◽  
Public Health Problem ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Major Public Health Problem ◽  
Peripheral Artery ◽  
Artery Disease

Diabetes mellitus is currently becoming a major public health problem in the world. The prevalence of diabetes mellitus globally in 2019 is estimated at 9.3% and will increase to 10.9% in 2040. Peripheral artery disease is one of the important complications of diabetes mellitus. Patients with diabetes mellitus accompanied by peripheral artery disease have high morbidity and. Therefore, early detection of peripheral artery disease in diabetic patients is important. This event is carried out with the aim of early detection of peripheral artery disease in diabetes mellitus sufferers in Mataram. A total of 183 diabetes mellitus patients at the Siti Hajar Hospital, Mataram, were participated in this event, with an average age of 57 years and 67.8% of them were women. Most of the patients (75.4%) had poor blood glucose control. Of these, 26.8% of patients had peripheral artery disease. Patients and/or caregivers showed high enthusiasm during the education regarding the detection results of the peripheral artery disease. This event was very useful in increasing the knowledge of diabetic patients, especially in terms of blood sugar control, prevention, and management of peripheral artery disease.

scholarly journals Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 198 ◽  
Author(s):  
Yee Lian Tiong ◽  
Khuen Yen Ng ◽  
Rhun Yian Koh ◽  
Gnanajothy Ponnudurai ◽  
Soi Moi Chye
Keyword(s):  
Oxidative Stress ◽  
Schwann Cells ◽  
High Glucose ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Ros Generation ◽  
Diabetic Patients ◽  
Glucose Treatment ◽  
Induced Apoptosis

Neuropathy is a complication that affects more than 50% of long-standing diabetic patients. One of the causes of diabetes neuropathy (DN) is the apoptosis of Schwann cells due to prolonged exposure to high glucose and build-up of oxidative stress. Melatonin is a hormone that has a known antioxidant property. In this study, we investigated the protective effect of melatonin on high glucose-induced Schwann cells’ apoptosis. Our results revealed that high glucose promoted apoptosis via mitochondrial-related oxidative stress and downregulated Bcl-2 family proteins in Schwann cells. In this signalling pathway, Bcl-2, Bcl-XL and Mcl-1 proteins were down-regulated while p-BAD and Puma proteins were up-regulated by high glucose treatment. Besides, we also proved that high glucose promoted apoptosis in Schwann cells through decreasing the p-NF-κB in the NF-κB signalling pathway. Key regulators of mTOR signalling pathway such as p-mTOR, Rictor and Raptor were also down-regulated after high glucose treatment. Additionally, high glucose treatment also decreased the Wnt signalling pathway downstream proteins (Wnt 5a/b, p-Lrp6 and Axin). Our results showed that melatonin treatment significantly inhibited high glucose-induced ROS generation, restored mitochondrial membrane potential and inhibited high glucose-induced apoptosis in Schwann cells. Furthermore, melatonin reversed the alterations of protein expression caused by high glucose treatment. Our results concluded that melatonin alleviates high glucose-induced apoptosis in Schwann cells through mitigating mitochondrial-related oxidative stress and the alterations of Bcl-2, NF-κB, mTOR and Wnt signalling pathways.

scholarly journals The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Zhen Zhang ◽  
Jing Li ◽  
Lei Yang ◽  
Rongping Chen ◽  
Rui Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
High Glucose ◽  
Pancreatic Beta Cells ◽  
Strong Predictor ◽  
Phase Cell ◽  
Antiproliferative Effects ◽  
Intermittent High Glucose ◽  
Normal Glucose ◽  
Related Proteins

Objectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms.Methods. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined.Results. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly.Conclusions. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.

scholarly journals Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xinhui Liu ◽  
Shiying Huang ◽  
Fochang Wang ◽  
Lin Zheng ◽  
Jiandong Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Mitochondrial Dynamics ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Public Health Problem ◽  
High Morbidity ◽  
Tubular Atrophy ◽  
Periodic Acid Schiff

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson’s trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

High-glucose stimulation of 64,000-Mr islet cell autoantigen expression

Diabetes ◽  
1989 ◽  
Vol 38 (10) ◽  
pp. 1326-1328 ◽  
Author(s):  
O. Kampe ◽  
A. Andersson ◽  
E. Bjork ◽  
A. Hallberg ◽  
F. A. Karlsson
Keyword(s):  
High Glucose ◽  
Islet Cell ◽  
Glucose Stimulation ◽  
Stimulation Of

High Glucose Affects the Cytotoxic Potential of Rapamycin, Metformin and Hydrogen Peroxide in Cultured Human Mesenchymal Stem Cells

2019 ◽  
Vol 19 (9) ◽  
pp. 688-698 ◽  
Author(s):  
Azam Roohi ◽  
Mahin Nikougoftar ◽  
Hamed Montazeri ◽  
Shadisadat Navabi ◽  
Fazel Shokri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
High Glucose ◽  
Cell Cycle Distribution ◽  
Efficient Treatment ◽  
Chronic Hyperglycemia ◽  
Placental Mesenchymal Stem Cells

Background: Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. Methods: Placental mesenchymal stem cells were treated with various concentrations of glucose, metformin, rapamycin, and hydrogen peroxide to monitor their viability and cell cycle distribution. Cellular viability was examined via the MTT assay. Cell cycle distribution was studied by propidium iodide staining and apoptosis was determined using Annexin Vpropidium iodide staining and flow cytometry. Involvement of potential signaling pathways was evaluated by Western blotting for activation of Akt, P70S6K, and AMPK. Results: The results indicated that high glucose augmented cell viability and reduced metformin toxic potential. However, the hydrogen peroxide and rapamycin toxicities were exacerbated. Conclusion: Our findings suggest that high glucose concentration has a major effect on placental mesenchymal stem cell viability in the presence of rapamycin, metformin and hydrogen peroxide in culture.

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