Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4/NF-κB/NLRP3 inflammasome pathway

Although the underlying mechanisms of diabetes-induced myocardial injury have not been fully illuminated, the inflammation reaction has been reported intently linked with diabetes. The nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, the key component of pyroptosis, is involved in inflammation reaction, which may be one of the important mechanisms in diabetes-induced myocardial injury. The purpose of this study was to investigate the changes of NLRP3 inflammasome and pyroptosis in high glucose-induced H9C2 cardiac cell injury and investigate whether overexpression of mitochondrial aldehyde dehydrogenase 2 (ALDH2) can reduce the occurrence of pyroptosis. The H9C2 cardiac cells were exposed to 35 mM glucose for 24 h to induce cytotoxicity. Mitochondrial ALDH2 overexpression cardiac cell line was constructed. The results showed in high glucose condition that ALDH2 overexpression significantly increased H9C2 cardiac cell viability, increased mitochondrial ALDH2 activity and protein expression, and reduced mitochondrial reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and lactate dehydrogenase (LDH) levels; meanwhile, the pyroptosis key components—NLRP3 inflammasome-related proteins, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cysteine-containing aspartate specific protease 1 (Caspase-1), and interleukin-18 (IL-18) protein expressions—were significantly decreased, and IL-18 and interleukin-1β (IL-1β) levels were also decreased. In high glucose-induced cardiac cell injury, ALDH2 overexpression may reduce ROS production, thereby inhibiting the activation of NLRP3 inflammation and cell pyroptosis. ALDH2 gene might play the potential role in the treatment of high glucose-induced H9C2 cardiac cell injury.

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Inhibitory effects and mechanism of 25-OH-PPD on glomerular mesangial cell proliferation induced by high glucose

Environmental Toxicology and Pharmacology ◽

10.1016/j.etap.2016.04.013 ◽

2016 ◽

Vol 44 ◽

pp. 93-98 ◽

Cited By ~ 4

Author(s):

Junxian Yu ◽

Chunna Liu ◽

Zhe Li ◽

Chao Zhang ◽

Zheng Wang ◽

...

Keyword(s):

Cell Proliferation ◽

High Glucose ◽

Mesangial Cell ◽

Inhibitory Effects ◽

Glomerular Mesangial Cell ◽

Mesangial Cell Proliferation

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Glomerular mesangial cell altered contractility in high glucose is Ca2+ independent

Diabetes ◽

10.2337/diabetes.44.7.759 ◽

1995 ◽

Vol 44 (7) ◽

pp. 759-766 ◽

Cited By ~ 7

Author(s):

R. D. Hurst ◽

Z. S. Stevanovic ◽

S. Munk ◽

B. Derylo ◽

X. Zhou ◽

...

Keyword(s):

High Glucose ◽

Mesangial Cell ◽

Glomerular Mesangial Cell

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Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes

Journal of Diabetes Research ◽

10.1155/2019/8151836 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Zhen Qiu ◽

Yuhong He ◽

Hao Ming ◽

Shaoqing Lei ◽

Yan Leng ◽

...

Keyword(s):

Cell Viability ◽

Nlrp3 Inflammasome ◽

High Glucose ◽

Cell Injury ◽

H9c2 Cell ◽

Ros Production ◽

H9c2 Cells ◽

Caspase 1 ◽

H9c2 Cardiomyocytes ◽

Hypoxia Reoxygenation

Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.

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