Sea cucumber, Stichopus japonicus ethyl acetate fraction modulates the lipopolysaccharide induced iNOS and COX-2 via MAPK signaling pathway in murine macrophages

This study aimed to investigate the high glucose damage on human retinal pigment epithelial (RPE) cells, the role of p38 MAPK signaling pathway and how dimethyl fumarate can regulate that. We carried out in vitro studies on ARPE-19 cells exposed to physiological and high glucose (HG) conditions, to evaluate the effects of DMF on cell viability, apoptosis, and expression of inflammatory and angiogenic biomarkers such as COX-2, iNOS, IL-1β, and VEGF. Our data have demonstrated that DMF treatment attenuated HG-induced apoptosis, as confirmed by reduction of BAX/Bcl-2 ratio. Furthermore, in RPE cells exposed to HG we observed a significant increase of iNOS, COX-2, and IL-1β expression, that was reverted by DMF treatment. Moreover, DMF reduced the VEGF levels elicited by HG, inhibiting p38 MAPK signaling pathway. The present study demonstrated that DMF provides a remarkable protection against high glucose-induced damage in RPE cells through p38 MAPK inhibition and the subsequent down-regulation of VEGF levels, suggesting that DMF is a small molecule that represents a good candidate for diabetic retinopathy treatment and warrants further in vivo and clinical evaluation.

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MAPK: A Key Player in the Development and Progression of Stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200613223018 ◽

2020 ◽

Vol 19 (4) ◽

pp. 248-256

Author(s):

Yangmin Zheng ◽

Ziping Han ◽

Haiping Zhao ◽

Yumin Luo

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Complex Disease ◽

Therapeutic Targets ◽

Cell Types ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Effective Prevention ◽

Prevention And Treatment ◽

Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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