scholarly journals Chronic intermittent hypoxia disturbs insulin secretion and causes pancreatic injury via the MAPK signaling pathway

2017 ◽  
Vol 95 (3) ◽  
pp. 415-420 ◽  
Author(s):  
Yeying Wang ◽  
Bing Hai ◽  
Xiaoqun Niu ◽  
Li Ai ◽  
Yu Cao ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Mapk Signaling ◽  
Pancreatic Tissue ◽  
Mapk Signaling Pathway ◽  
Chronic Intermittent Hypoxia ◽  
Dependent Manner

Obstructive sleep apnea (OSA) is a breathing disorder during sleep, with a most prominent character of chronic intermittent hypoxia (CIH), which induces the generation of reactive oxygen species (ROS) that damages multiple tissues and causes metabolic disorders. In this study, we established a rat model of varying OSA with different grades of CIH (12.5% O2, 10% O2, 7.5% O2, and 5% O2) for 12 weeks, and found that CIH stimulated insulin secretion, reduced the insulin:proinsulin ratio in pancreatic tissue, and caused pancreatic tissue lesions and cell apoptosis in a dose-dependent manner. Moreover, CIH promoted the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and activated mitogen-activated protein kinase (MAPK) family members, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and P38, depending on the O2 concentration. In summary, CIH disturbed insulin secretion, and caused inflammation, lesions, and cell apoptosis in pancreatic tissue via the MAPK signaling pathway, which may be of great significance for clinical treatment of OSA and type 2 diabetes mellitus (T2DM).

scholarly journals Chronic Intermittent Hypoxia Reduces the Effects of Glucosteroid in Asthma via Activating the p38 MAPK Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Liang ◽  
Xin Gu ◽  
Hai Ji Shen ◽  
Yu Heng Shi ◽  
Yao Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Intermittent Hypoxia ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Chronic Intermittent Hypoxia ◽  
Stress Injury ◽  
P38 Mapk Pathway

AimsObstructive sleep apnea (OSA) is a risk factor for steroid-resistant (SR) asthma. However, the underlying mechanism is not well defined. This study aimed to investigate how chronic intermittent hypoxia (CIH), the main pathophysiology of OSA, influenced the effects of glucocorticoids (GCs) on asthma.Main MethodsThe effects of dexamethasone (Dex) were determined using the ovalbumin (OVA)-challenged mouse model of asthma and transforming growth factor (TGF)-β treated airway smooth muscle cells (ASMCs), with or without CIH. The p38 MAPK signaling pathway activity was then detected in the mouse (n = 6) and ASMCs models (n = 6), which were both treated with the p38 MAPK inhibitor SB239063.Key FindingsUnder CIH, mouse pulmonary resistance value, inflammatory cells in bronchoalveolar lavage fluid (BALF), and inflammation scores increased in OVA-challenged combined with CIH exposure mice compared with OVA-challenged mice (p < 0.05). These indicators were similarly raised in the OVA + CIH + Dex group compared with the OVA + Dex group (P < 0.05). CIH exposure enhanced the activation of the p38 MAPK pathway, oxidative stress injury, and the expression of NF-κB both in lung tissue and ASMCs, which were reversed by treatment with Dex and SB239063. In the in vitro study, treatment with Dex and SB239063 decreased ASMCs proliferation induced by TGF-β combined with CIH and suppressed activation of the p38 MAPK pathway, oxidative stress injury, and NF-κB nuclear transcription (p < 0.05).SignificanceThese results indicated that CIH decreased GC sensitivity by activating the p38 MAPK signaling pathway.

scholarly journals Dietary nitrate supplementation prevents radiotherapy-induced xerostomia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaoyu Feng ◽  
Zhifang Wu ◽  
Junji Xu ◽  
Yipu Xu ◽  
Bin Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Parotid Gland ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Dependent Manner ◽  
Dietary Nitrate ◽  
Gland Tissue ◽  
Nitrate Supplementation

Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Here, we investigated the effect of dietary nitrate on the prevention and treatment of IR-induced parotid gland hypofunction in miniature pigs, and elucidated the underlying mechanism in human parotid gland cells (hPGCs). We found that nitrate administration prevented IR-induced parotid gland damage in a dose-dependent manner, by maintaining the function of irradiated parotid gland tissue. Nitrate could increase sialin expression, a nitrate transporter expressed in the parotid gland, making the nitrate-sialin feedback loop that facilitates nitrate influx into cells for maintaining cell proliferation and inhibiting apoptosis. Furthermore, nitrate enhanced cell proliferation via the epidermal growth factor receptor (EGFR)-protein kinase B (AKT)-mitogen-activated protein kinase (MAPK) signaling pathway in irradiated parotid gland tissue. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR–AKT-MAPK signaling pathway. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induce xerostomia.

scholarly journals Protective Effect of Penetratin Analogue-Tagged SOD1 on Cisplatin-Induced Nephrotoxicity through Inhibiting Oxidative Stress and JNK/p38 MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiao-lu Wang ◽  
Liang Wang ◽  
Fo-lan Lin ◽  
Si-si Li ◽  
Ting-xuan Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Membrane ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Tunel Assay ◽  
Mapk Signaling Pathway ◽  
Mapk Activation ◽  
Urea Nitrogen

Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.

scholarly journals Protective effects of alfalfa saponins on oxidative stress-induced apoptotic cells

2020 ◽  
Vol 11 (9) ◽  
pp. 8133-8140
Author(s):  
Yalei Cui ◽  
Boshuai Liu ◽  
Xiao Sun ◽  
Zidan Li ◽  
Yanyan Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Antioxidant System ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Apoptotic Cells ◽  
Protective Effects

Alfalfa saponins defend against oxidative stress by enhancing the antioxidant system and further inhibit cell apoptosis by activating the MAPK signaling pathway.

Astragaloside attenuates lipopolysaccharide‐induced cell apoptosis in human gingiva cells via MAPK signaling pathway

2019 ◽  
Vol 120 (8) ◽  
pp. 12273-12279 ◽  
Author(s):  
Xionghu Shen ◽  
Honghua Sun ◽  
Hai Cui ◽  
Yongmin Jin ◽  
Wenbo Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Human Gingiva
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