PPAR<i>γ</i> Attenuates Interleukin‐1<i>β</i>‐Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes

Ni, Su; Liu, Dong; Wei, Hui; Miao, Kaisong; Chen, Zhuang

doi:10.1155/2021/5551338

Cited by 26 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This cannot attribute to the inhibition of mitochondria by DPI, for RBCs lack mitochondria. It is hard to explain based on the present data, but it is a common result that DPI cannot inhibit ROS levels to the control group level in many other studies [ 35 , 36 ].…”

Section: Resultscontrasting

confidence: 54%

Xanthohumol Induces ROS through NADPH Oxidase, Causes Cell Cycle Arrest and Apoptosis

Wang

Zhao

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are either toxic in excess or essential for redox signalling at the physiological level, which is closely related to the site of generation. Xanthohumol (XN) is an important natural product of hops (Humulus lupulus L.) and was reported to induce ROS in mitochondria. While in the present study, our data indicate that NADPH oxidase (NOX) is another site. In human acute myeloid leukemia HL-60 cells, we first identified that cell proliferation was inhibited by XN without affecting viability, and this could be alleviated by the antioxidant N-acetyl-L-cysteine (NAC); cell cycles were blocked at G1 phase, apoptosis was induced in a dose-dependent manner, and malondialdehyde (MDA) content was upregulated. XN-induced ROS generation was detected by flow cytometry, which can be inhibited by diphenyleneiodonium chloride (DPI, a NOX inhibitor), while not by NG-methyl-L-arginine acetate (L-NMMA, a nitric oxide synthase inhibitor). The involvement of NOX in XN-induced ROS generation was further evaluated: immunofluorescence assay indicated subunits assembled in the membrane, and gp91phox knockdown with siRNA decreased XN-induced ROS. Human red blood cells (with NOX, without mitochondria) were further selected as a cell model, and the XN-induced ROS and DPI inhibiting effects were found again. In conclusion, our results indicate that XN exhibits antiproliferation effects through ROS-related mechanisms, and NOX is a source of XN-induced ROS. As NOX-sourced ROS are critical for phagocytosis, our findings may contribute to the anti-infection and anti-inflammatory effect of XN.

show abstract

Section: Resultscontrasting

confidence: 54%

Xanthohumol Induces ROS through NADPH Oxidase, Causes Cell Cycle Arrest and Apoptosis

Wang

Zhao

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…As a nuclear receptor transcription factor, PPAR γ is involved in the regulation of ROS by regulating redox and biosynthetic processes in mitochondria [ 54 , 55 ]. Activation of PPAR γ inhibited oxidative stress and also negatively regulated the expression of AP-1, NF- κ B, and other inflammatory response genes [ 56 ]. In the present study, PPAR γ was found through the intersection of prediction target genes of vitexin and inflammatory disease-related genes.…”

Section: Discussionmentioning

confidence: 99%

Vitexin Mitigates Staphylococcus aureus-Induced Mastitis via Regulation of ROS/ER Stress/NF-κB/MAPK Pathway

Chen

Yang

Huang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Mastitis, caused by a variety of pathogenic microorganisms, seriously threatens the safety and economic benefits of the dairy industry. Vitexin, a flavone glucoside found in many plant species, has been widely reported to have antioxidant, anti-inflammatory, antiviral, anticancer, neuroprotective, and cardioprotective effects. However, few studies have explored the effect of vitexin on mastitis. This study is aimed at exploring whether the antioxidant and anti-inflammatory functions of vitexin can improve Staphylococcus aureus-induced mastitis and its possible molecular mechanism. The expression profiles of S. aureus-infected bovine mammary epithelial cells and gland tissues from the GEO data set (GSE94056 and GSE139612) were analyzed and found that DEGs were mainly involved in immune signaling pathways, apoptosis, and ER stress through GO and KEGG enrichment. Vitexin blocked the production of ROS and increased the activity of antioxidant enzymes (SOD, GSH-PX, and CAT) via activation of PPARγ in vivo and in vitro. In addition, vitexin reduced the production of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and inhibited apoptosis in MAC-T cells and mouse mammary tissues infected with Staphylococcus aureus. Moreover, vitexin decreased the expression of PDI, Ero1-Lα, p-IRE1α, PERK, p-eIF2α, and CHOP protein but increased BiP in both mammary gland cells and tissues challenged by S. aureus. Western blot results also found that the phosphorylation levels of JNK, ERK, p38, and p65 were reduced in vitexin-treated tissues and cells. Vitexin inhibited the production of ROS through promoting PPARγ, increased the activity of antioxidant enzymes, and reduced inflammatory cytokines and apoptosis by alleviating ER stress and inactivation MAPKs and NF-κB signaling pathway. Vitexin maybe have great potential to be a preventive and therapeutic agent for mastitis.

show abstract

“…NOX4 forms a heterodimer with p22phox without a cytosolic subunit. Several studies have consistently reported the critical roles of NOX2 and NOX4 in OA [ 30 ]. NOX2 is weakly expressed in normal chondrocytes but increases in OA and IL-1β-treated chondrocytes [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NADPH Oxidases Prevents the Development of Osteoarthritis

Han

Park

et al. 2022

Antioxidants

View full text Add to dashboard Cite

Increased oxidative stress in osteoarthritis (OA) cartilage mediates catabolic signal transduction leading to extracellular matrix degradation and chondrocyte apoptosis. This study aimed to explore the contribution of NADPH oxidase (NOX), a major source of cellular reactive oxygen species (ROS), to the catabolic process of chondrocytes and to OA. The inhibition of NOX isoforms with a pan-NOX inhibitor, APX-115, significantly decreased IL-1β-induced ROS production in primary chondrocytes and, most potently, suppressed the expression of oxidative stress marker genes and catabolic proteases compared with the inhibition of other ROS sources. Catabolic stimuli by IL-1β treatment and in post-traumatic OA conditions upregulated the expression of NOX2 and NOX4 in chondrocytes. In the post-traumatic OA model, the pharmacologic inhibition of NOX protected mice against OA by modulating the oxidative stress and the expression of MMP-13 and Adamts5 in chondrocytes. Mechanistically, NOX inhibition suppresses Rac1, p38, and JNK MAPK signaling consistently and restores oxidative phosphorylation in IL-1β-treated chondrocytes. In conclusion, NOX inhibition prevented the development of OA by attenuating the catabolic signaling and restoring the mitochondrial metabolism and can thus be a promising class of drug for OA.

show abstract

PPARγ Attenuates Interleukin‐1β‐Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes

Cited by 26 publications

References 41 publications

Xanthohumol Induces ROS through NADPH Oxidase, Causes Cell Cycle Arrest and Apoptosis

Xanthohumol Induces ROS through NADPH Oxidase, Causes Cell Cycle Arrest and Apoptosis

Vitexin Mitigates Staphylococcus aureus-Induced Mastitis via Regulation of ROS/ER Stress/NF-κB/MAPK Pathway

Inhibition of NADPH Oxidases Prevents the Development of Osteoarthritis

Contact Info

Product

Resources

About