The Involvement of ERK1/2 and p38 MAPK in the Premature Senescence of Melanocytes Induced by H2O2 Through a p53-Independent p21 Pathway

2022 ◽  
Author(s):  
Xiaoyuan Hou ◽  
Jiaqi Shi ◽  
Li Sun ◽  
Lebin Song ◽  
Wene Zhao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Premature Senescence

Long-term exposure to TNF-α leads human skin fibroblasts to a p38 MAPK- and ROS-mediated premature senescence

2018 ◽  
Vol 19 (3-4) ◽  
pp. 237-249 ◽  
Author(s):  
Eleni Mavrogonatou ◽  
Angeliki Konstantinou ◽  
Dimitris Kletsas
Keyword(s):  
Human Skin ◽  
P38 Mapk ◽  
Skin Fibroblasts ◽  
Premature Senescence ◽  
Human Skin Fibroblasts ◽  
Tnf Α

scholarly journals The HBP1 Transcriptional Repressor Participates in RAS-Induced Premature Senescence

2006 ◽  
Vol 26 (22) ◽  
pp. 8252-8266 ◽  
Author(s):  
Xiaowei Zhang ◽  
Jiyoung Kim ◽  
Robin Ruthazer ◽  
Michael A. McDevitt ◽  
David E. Wazer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
P38 Mapk ◽  
Clinical Relevance ◽  
Transcriptional Repressor ◽  
Initial Step ◽  
Mapk Signaling ◽  
Premature Senescence ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Oncogenic Pathways

ABSTRACT Oncogene-mediated premature senescence has emerged as a potential tumor-suppressive mechanism in early cancer transitions. Previous work shows that RAS and p38 MAPK participate in premature senescence, but transcriptional effectors have not been identified. Here, we demonstrate that the HBP1 transcriptional repressor participates in RAS- and p38 MAPK-induced premature senescence. In cell lines, we had previously isolated HBP1 as a retinoblastoma (RB) target but have determined that it functions as a proliferation regulator by inhibiting oncogenic pathways as a transcriptional repressor. In primary cells, the results indicate that HBP1 is a necessary component of premature senescence by RAS and p38 MAPK. Similarly, a knockdown of WIP1 (a p38 MAPK phosphatase) induced premature senescence that also required HBP1. Furthermore, HBP1 requires regulation by RB, in which few transcriptional regulators for premature senescence have been shown. Together, the data suggest a model in which RAS and p38 MAPK signaling engage HBP1 and RB to trigger premature senescence. As an initial step toward clinical relevance, a bioinformatics approach shows that the relative expression levels of HBP1 and WIP1 correlated with decreased relapse-free survival in breast cancer patients. Together, these studies highlight p38 MAPK, HBP1, and RB as important components for a premature-senescence pathway with possible clinical relevance to breast cancer.

Role of p38 MAPK pathway in BMP4-mediated Smad-dependent premature senescence in lung cancer cells

2010 ◽  
Vol 433 (2) ◽  
pp. 333-343 ◽  
Author(s):  
Dongmei Su ◽  
Xiue Peng ◽  
Shan Zhu ◽  
Ying Huang ◽  
Zhixiong Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Biological Effects ◽  
Lung Cancer Cells ◽  
Signalling Pathways ◽  
Premature Senescence ◽  
P38 Mapk Pathway

BMP4 (bone morphogenetic protein 4) is a multifunctional cytokine known to exert its biological effects through a variety of signalling pathways. The diverse function of BMP4 appears to be due to multiple pathways activated by BMP4 itself. Our previous studies have demonstrated that BMP4 is able to drive lung cancer cells into a process of premature senescence; however, the signalling pathways, as well their interplays and roles associated with this process, are not well understood. To address these questions, in the present study we investigated the signalling and molecular mechanisms underlying the BMP4-induced senescence, and our data demonstrated that p38 MAPK (mitogen-activated protein kinase) and Smad pathways were necessary for this process. Meanwhile, the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which is required for senescence, was not activated by BMP4 in the lung cancer cell line NCI-H460. We also showed that the BMP4-responsive R-Smads (receptor-regulated Smads), i.e. Smad1 and Smad5, were necessary for the up-regulation of p16INK4a and p21WAF1/cip1 and for the induction of premature senescence. Furthermore, we found that activation of the p38 MAPK pathway by BMP4 was essential for the full activation of transcription potential of Smad1/5. Overall, the results of the present study implicate a complex co-operation between p38 MAPK and Smad pathways in BMP4-mediated premature senescence.

Hyperosmotischer Stress induziert Interleukin 8 via p38 MAPK, Src-Kinase und EGRF in humanen Atemwegszellen

Pneumologie ◽  
2012 ◽  
Vol 66 (S 01) ◽  
Author(s):  
SM Loitsch ◽  
A Langanke ◽  
TOF Wagner ◽  
TO Hirche
Keyword(s):  
P38 Mapk ◽  
Src Kinase ◽  
Interleukin 8

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

Role of the p38 MAPK Pathway in Induction of iNOS Expression in Human Leukocytes

2008 ◽  
Vol 56 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Ewa Jablonska ◽  
Wioletta Ratajczak ◽  
Jakub Jablonski
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Inos Expression ◽  
Human Leukocytes ◽  
P38 Mapk Pathway
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