scholarly journals Myt3 suppression sensitizes islet cells to high glucose-induced cell death via Bim induction

2016 ◽  
Vol 7 (5) ◽  
pp. e2233-e2233 ◽  
Author(s):  
B R Tennant ◽  
B Vanderkruk ◽  
J Dhillon ◽  
D Dai ◽  
C B Verchere ◽  
...  
Keyword(s):  
Cell Death ◽  
High Glucose ◽  
Islet Cells

scholarly journals Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress

Islets ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 57-64 ◽  
Author(s):  
You Jeong Kim ◽  
Su Min Park ◽  
Hye Sook Jung ◽  
Eun Ju Lee ◽  
Tae Kyoon Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
High Glucose ◽  
Ginsenoside Rg3 ◽  
Intermittent High Glucose

scholarly journals Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1865
Author(s):  
Andris Elksnis ◽  
Jing Cen ◽  
Per Wikström ◽  
Per-Ola Carlsson ◽  
Nils Welsh
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Insulin Release ◽  
Mitochondrial Function ◽  
High Glucose ◽  
Human Islet ◽  
Sodium Palmitate ◽  
Nadph Oxidase 4

Previous studies have reported beneficial effects of NADPH oxidase 4 (NOX4) inhibition on beta-cell survival in vitro and in vivo. The mechanisms by which NOX4 inhibition protects insulin producing cells are, however, not known. The aim of the present study was to investigate the effects of a pharmacological NOX4 inhibitor (GLX7013114) on human islet and EndoC-βH1 cell mitochondrial function, and to correlate such effects with survival in islets of different size, activity, and glucose-stimulated insulin release responsiveness. We found that maximal oxygen consumption rates, but not the rates of acidification and proton leak, were increased in islets after acute NOX4 inhibition. In EndoC-βH1 cells, NOX4 inhibition increased the mitochondrial membrane potential, as estimated by JC-1 fluorescence; mitochondrial reactive oxygen species (ROS) production, as estimated by MitoSOX fluorescence; and the ATP/ADP ratio, as assessed by a bioluminescent assay. Moreover, the insulin release from EndoC-βH1 cells at a high glucose concentration increased with NOX4 inhibition. These findings were paralleled by NOX4 inhibition-induced protection against human islet cell death when challenged with high glucose and sodium palmitate. The NOX4 inhibitor protected equally well islets of different size, activity, and glucose responsiveness. We conclude that pharmacological alleviation of NOX4-induced inhibition of beta-cell mitochondria leads to increased, and not decreased, mitochondrial ROS, and this was associated with protection against cell death occurring in different types of heterogeneous islets. Thus, NOX4 inhibition or modulation may be a therapeutic strategy in type 2 diabetes that targets all types of islets.

scholarly journals MicroRNA-21, induced by high glucose, modulates macrophage apoptosis via programmed cell death 4

2012 ◽  
Vol 12 (1) ◽  
pp. 463-469 ◽  
Author(s):  
YUAN-YUAN SHANG ◽  
NING-NING FANG ◽  
FENG WANG ◽  
HUI WANG ◽  
ZHI-HAO WANG ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
High Glucose ◽  
Macrophage Apoptosis ◽  
Programmed Cell Death 4

scholarly journals Distinct downstream signaling and the roles of VEGF and PlGF in high glucose-mediated injuries of human retinal endothelial cells in culture

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wanzhen Jiao ◽  
Jia-Fu Ji ◽  
Wenwen Xu ◽  
Wenjuan Bu ◽  
Yuanjie Zheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Growth Factor ◽  
High Glucose ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Blood Retinal Barrier ◽  
Western Blots ◽  
Retinal Endothelial Cells ◽  
Protein Levels

Abstract Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) plays a crucial role in breakdown of the blood-retinal barrier due to hyperpermeability in diabetic retinopathy (DR). However, the distinct signaling driven by VEGF and PlGF in the pathogenesis of DR remains unclear. In this study, we investigated VEGF- and PlGF- related signaling pathways and their roles in cultured human microvascular retinal endothelial cells (hRECs) under high glucose conditions (HG; 25 mM). Apoptotic cell death was evaluated, and FITC conjugated bovine serum albumin across monolayer hRECs served as an index of permeability. Western blots were used to assess the protein levels of VEGF and PlGF, as well as the phosphorylation of p38MAPK, STAT1 and Erk1/2. Knockdown of VEGF and PlGF was performed by using siRNA. Following HG treatment, increases of VEGF and PlGF as well as PKC activity were detected in hRECs. Increased phosphorylations of p38MAPKThr180/Thr182, STAT1Ser727, and Erk1/2Tyr202/Tyr185 as well as VEGFR1Tyr1213 and VEGFR2Tyr1175 were also detected in HG-treated hRECs. Inhibition of PKC activity by Go 6976 prevented HG-induced increases of phosphor-Erk1/2 and nitric oxide synthase (NOS1) expressions as well as hyperpermeability, whereas inhibition of p38MAPK pathway by SB203580 selectively suppressed activation of STAT1 and decreased apoptotic cell death under HG conditions. Moreover, VEGF knockdown predominantly inhibited activation of VEGFR2, and phosphorylation of p38MAPK and STAT1, as well as apoptotic cell death in HG-treated hRECs. Nevertheless, PlGF knockdown mainly suppressed phosphorylation of VEGFR1, PKC, and Erk1/2, as well as NOS1 expressions and hyperpermeability. Taken together, we provide evidence demonstrating that HG-induced elevation of PlGF is responsible for hyperpermeability mainly through increasing activation of PKC-Erk1/2-NOS axis via VEGFR1, while HG-induced elevation of VEGF is associated with induction of apoptotic cell death mainly through increasing activation of p38MAPK/STAT1 signaling via VEGFR2.

scholarly journals ZnCl2 sustains the adriamycin-induced cell death inhibited by high glucose

2016 ◽  
Vol 7 (6) ◽  
pp. e2280-e2280 ◽  
Author(s):  
A Garufi ◽  
D Trisciuoglio ◽  
M Cirone ◽  
G D'Orazi
Keyword(s):  
Cell Death ◽  
High Glucose

scholarly journals High glucose induces cell death of cultured human aortic smooth muscle cells through the formation of hydrogen peroxide

2001 ◽  
Vol 133 (7) ◽  
pp. 967-974 ◽  
Author(s):  
Concepción Peiró ◽  
Nuria Lafuente ◽  
Nuria Matesanz ◽  
Elena Cercas ◽  
José L Llergo ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

scholarly journals High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature

2016 ◽  
Vol 112 (3) ◽  
pp. 656-668 ◽  
Author(s):  
Fulong Wang ◽  
Jocelyn Jia ◽  
Nathaniel Lal ◽  
Dahai Zhang ◽  
Amy Pei-Ling Chiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
High Glucose ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neutralizing Antibody ◽  
Metabolic Adaptation ◽  
Rat Cardiomyocytes ◽  
Altered Expression ◽  
And Function

Aims The secretion of enzymatically active heparanase (HepA) has been implicated as an essential metabolic adaptation in the heart following diabetes. However, the regulation and function of the enzymatically inactive heparanase (HepL) remain poorly understood. We hypothesized that in response to high glucose (HG) and secretion of HepL from the endothelial cell (EC), HepL uptake and function can protect the cardiomyocyte by modifying its cell death signature. Methods and results HG promoted both HepL and HepA secretion from microvascular (rat heart micro vessel endothelial cells, RHMEC) and macrovascular (rat aortic endothelial cells, RAOEC) EC. However, only RAOEC were capable of HepL reuptake. This occurred through a low-density lipoprotein receptor-related protein 1 (LRP1) dependent mechanism, as LRP1 inhibition using small interfering RNA (siRNA), receptor-associated protein, or an LRP1 neutralizing antibody significantly reduced uptake. In cardiomyocytes, which have a negligible amount of heparanase gene expression, LRP1 also participated in the uptake of HepL. Exogenous addition of HepL to rat cardiomyocytes produced a dramatically altered expression of apoptosis-related genes, and protection against HG and H2O2 induced cell death. Cardiomyocytes from acutely diabetic rats demonstrated a robust increase in LRP1 expression and levels of heparanase, a pro-survival gene signature, and limited evidence of cell death, observations that were not apparent following chronic and progressive diabetes. Conclusion Our results highlight EC-to-cardiomyocyte transfer of heparanase to modulate the cardiomyocyte cell death signature. This mechanism was observed in the acutely diabetic heart, and its interruption following chronic diabetes may contribute towards the development of diabetic cardiomyopathy.

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