Oxidative stress and phthalate-induced down-regulation of steroidogenesis in MA-10 Leydig cells

Introduction: Shear stress forces play an integral role in dictating the endothelial cell (EC) response to changes in blood flow, pro-inflammatory response and hence development of atherosclerosis. Previously, our group has identified EC microRNA-155 (miR-155) as one of the key signature dysregulated miRNAs in areas of chronic low magnitude oscillatory shear stress (OSS) in vasculature and OSS models of in-vitro. Hypothesis: we hypothesized that acute induction of OSS mediates EC oxidative stress, inflammation and dysfunction, via dysregulation of EC miR-155. Methods: 12-week old C57B/6J mice were subjected to abdominal aortic coarctation (AAC), a unique model of acute induction of OSS, for 3 days and downstream segments of acute OSS were compared to upstream unidirectional shear stress (USS) segments of the thoracic aorta. Results: Acute OSS resulted in down regulation of EC miR-155 expression and inverse upregulation of EC RhoA and Myosin light chain kinase (MYLK), known targets of miR-155-mediated EC cytoskeleton organization, in OSS segments compared with USS. This was associated with impaired EC dependent relaxation, differential contractile response to phenylephrine, and loss of EC barrier function as evaluated by extravasation of Evans-blue dye assay. In parallel, En-face immunohistochemical staining also showed increased expression of EC nitric oxide synthase (eNOS) along with increased levels of reactive oxygen species (ROS) and nitrotyrosine (NY) formation in OSS segments compared with USS. Conclusions: Together, our studies shed light on the early changes in EC response to acute induction of OSS and resulting down-regulation of EC mir-155, including; oxidative/inflammatory stress, EC dysfunction, loss of barrier function and cytoskeletal changes. Despite the early upregulation of eNOS, it could also potentially synergize with the activation of the RhoA-MYLK pathway in EC oxidative (ROS/NY)/inflammatory stress and associated EC dysfunction. Further studies are in progress to dissect the interplay between these different pathways and their causal relationships as downstream targets of EC miR-155.

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Vulnerability of neurons with mitochondrial dysfunction to oxidative stress is associated with down-regulation of thioredoxin

Neurochemistry International ◽

10.1016/j.neuint.2006.09.007 ◽

2007 ◽

Vol 50 (2) ◽

pp. 379-385 ◽

Cited By ~ 22

Author(s):

Jing Gao ◽

Zeng-Rong Zhu ◽

Hong-Qun Ding ◽

Zhongming Qian ◽

Li Zhu ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Down Regulation

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Fermentation of Panax notoginseng root extract polysaccharides attenuates oxidative stress and promotes type I procollagen synthesis in human dermal fibroblast cells

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03197-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shiquan You ◽

Xiuqin Shi ◽

Dan Yu ◽

Dan Zhao ◽

Quan An ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Oxidative Damage ◽

Signaling Pathway ◽

Dermal Fibroblast ◽

Panax Notoginseng ◽

Human Dermal Fibroblast ◽

Down Regulation ◽

Smad Signaling ◽

Smad Signaling Pathway

Abstract Background Panax notoginseng is one of the most valuable traditional Chinese medicines. Polysaccharides in P. notoginseng has been shown to significantly reduce the incidence of human diseases. However the application of fermentation technology in Panax notoginseng is not common, and the mechanism of action of P. notoginseng polysaccharides produced by fermentation is still unclear. The specific biological mechanisms of fermented P. notoginseng polysaccharides (FPNP) suppresses H2O2-induced apoptosis in human dermal fibroblast (HDF) and the underlying mechanism are not well understood. Methods In this study, the effects of water extracted and fermentation on concentration of polysaccharides in P. notoginseng extracts were analyzed. After the H2O2-induced HDF model of oxidative damage was established, and then discussed by the expression of cell markers, including ROS, MDA, SOD, CAT, GSH-Px and MMP-1, COL-I, ELN, which were detected by related ELISA kits. The expression of TGF-β/Smad pathway markers were tested by qRT-PCR to determine whether FPNP exerted antioxidant activity through TGF-β signaling in HDF cells. Results The polysaccharide content of Panax notoginseng increased after Saccharomyces cerevisiae CGMCC 17452 fermentation. In the FPNP treatment group, ROS and MDA contents were decreased, reversed the down-regulation of the antioxidant activity and expression of antioxidant enzyme (CAT, GSH-Px and SOD) induced by H2O2. Furthermore, the up-regulation in expression of TGF-β, Smad2/3 and the down-regulation in the expression of Smad7 in FPNP treated groups revealed that FPNP can inhibit H2O2-induced collagen and elastin injury by activating TGF-β/Smad signaling pathway. Conclusion It was shown that FPNP could inhibit the damage of collagen and elastin induced by H2O2 by activating the TGF-β/Smad signaling pathway, thereby protecting against the oxidative damage induced by hydrogen peroxide. FPNP may be an effective attenuating healing agent that protects the skin from oxidative stress and wrinkles.

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