Zinc rescues obesity-induced cardiac hypertrophy via
 stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/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.

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Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2013.02.027 ◽

2013 ◽

Vol 60 ◽

pp. 168-176 ◽

Cited By ~ 58

Author(s):

Xiaoming Li ◽

Xiaoli Wang ◽

Cuiyan Han ◽

Xiaoli Wang ◽

Guihua Xing ◽

...

Keyword(s):

Oxidative Stress ◽

P38 Mapk ◽

Hepatic Stellate Cells ◽

Mapk Pathway ◽

Stellate Cells ◽

Astragaloside Iv ◽

Collagen Production ◽

P38 Mapk Pathway ◽

Activated Hepatic Stellate Cells

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Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/8715185 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 14

Author(s):

Xuezhong Gong ◽

Yiru Duan ◽

Junli Zheng ◽

Yiquan Wang ◽

Guohua Wang ◽

...

Keyword(s):

Oxidative Stress ◽

P38 Mapk ◽

Mapk Pathway ◽

Contrast Induced Nephropathy ◽

Tubular Cells ◽

Renal Tubular Cells ◽

P38 Mapk Pathway ◽

Thioredoxin 1 ◽

Renal Tubular

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI) due to apoptosis induced in renal tubular cells. Our previous study demonstrated the novel N-acetylcysteine amide (NACA); the amide form of N-acetyl cysteine (NAC) prevented renal tubular cells from contrast-induced apoptosis through inhibiting p38 MAPK pathway in vitro. In the present study, we aimed to compare the efficacies of NACA and NAC in preventing CIN in a well-established rat model and investigate whether thioredoxin-1 (Trx1) and apoptosis signal-regulating kinase 1 (ASK1) act as the potential activator for p38 MAPK. NACA significantly attenuated elevations of serum creatinine, blood urea nitrogen, and biomarkers of AKI. At equimolar concentration, NACA was more effective than NAC in reducing histological changes of renal tubular injuries. NACA attenuated activation of p38 MAPK signal, reduced oxidative stress, and diminished apoptosis. Furthermore, we demonstrated that contrast exposure resulted in Trx1 downregulation and increased ASK1/p38 MAPK phosphorylation, which could be reversed by NACA and NAC. To our knowledge, this is the first report that Trx1 and ASK1 are involved in CIN. Our study highlights a renal protective role of NACA against CIN through modulating Trx1 and ASK1/p38 MAPK pathway to result in the inhibition of apoptosis among renal cells.

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