Microtubule depolymerization in Caenorhabditis elegans touch receptor neurons reduces gene expression through a p38 MAPK pathway

The pituitary transcription factor Pit-1 regulates hormonal production from the anterior pituitary gland. However, the mechanisms by which Pit-1 gene expression is regulated in humans are poorly understood. Activin, a member of the TGFβ superfamily, acts as a negative regulator of cell growth and prolactin gene expression in lactotrope cells. In this study, we show that activin negatively regulates the human Pit-1 gene promoter. We defined a 117-bp element within the Pit-1 promoter that is sufficient to relay these inhibitory effects. We further investigated the signaling pathways that mediate activin-induced inhibition of Pit-1 gene promoter in pituitary lactotrope cells. We found that the activin effects on Pit-1 gene regulation are Smad independent and require the p38 MAPK pathway. Specifically, blocking p38 kinase activity reverses activin-mediated inhibition of the Pit-1 gene promoter. Together, our results highlight the p38 MAPK pathway as a key regulator of activin function in pituitary lactotrope cells and further emphasizes the critical role played by activin in regulating hormonal production in the pituitary gland.

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Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000494788 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1687-1697 ◽

Cited By ~ 10

Author(s):

Yichun Xu ◽

Hui Yao ◽

Qiyou Wang ◽

Wenbin Xu ◽

Kaihua Liu ◽

...

Keyword(s):

Gene Expression ◽

Oxidative Damage ◽

P38 Mapk ◽

Cell Apoptosis ◽

Caspase 3 ◽

Mapk Pathway ◽

Aquaporin 3 ◽

P38 Mapk Pathway ◽

Intracellular Ros ◽

Cellular Apoptosis

Background/Aims: Previous studies have shown that oxidative damage is a main contributor to disc nucleus pulposus (NP) cell apoptosis. Aquaporin-3 (AQP-3) facilitates reactive oxygen species (ROS) scavenging and thus alleviates oxidative injury in other cells. This study aims to investigate the role and mechanism of AQP-3 in regulating NP cell apoptosis under oxidative damage. Methods: Rat NP cells were treated with H2O2 for 48 hours, while control NP cells were free of H2O2. Recombinant AQP-3 lentiviral vectors were used to investigate the effect of enhanced AQP-3 expression levels in NP cells. NP cell apoptosis was assessed by flow cytometry, caspase-3 activity, gene expression of apoptosis-related molecules (Bax, Bcl-2 and caspase-3), and protein expression of cellular apoptosis markers (cleaved PARP and cleaved caspase-3). Additionally, intracellular ROS content and activity of the p38 MAPK pathway were evaluated. Results: Compared with the control NP cells, oxidative damage in the treatment cells significantly increased cell apoptosis ratios and caspase-3 activity, upregulated gene expression of Bax and caspase-3, downregulated gene expression of Bcl-2, and increased protein expression of cleaved PARP and cleaved caspase-3, as well as increased intracellular ROS content and activity of the p38 MAPK pathway. However, AQP-3 overexpression partly alleviated cell apoptosis, decreased intracellular ROS content, and inhibited the p38 MAPK pathway in NP cells under oxidative damage. Conclusion: Oxidative damage can significantly downregulate AQP-3 expression. Enhancing AQP-3 expression in NP cells partly attenuates cellular apoptosis through regulating the p38 MAPK pathway under oxidative damage.

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Mechanism of AP-1-mediated gene expression by select organochlorines through the p38 MAPK pathway

Carcinogenesis ◽

10.1093/carcin/bgh009 ◽

2003 ◽

Vol 25 (2) ◽

pp. 249-261 ◽

Cited By ~ 62

Author(s):

D. E. Frigo

Keyword(s):

Gene Expression ◽

P38 Mapk ◽

Mapk Pathway ◽

P38 Mapk Pathway

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IGLR-2, a Leucine-Rich Repeat Domain Containing Protein, Is Required for the Host Defense in Caenorhabditis elegans

Frontiers in Immunology ◽

10.3389/fimmu.2020.561337 ◽

2020 ◽

Vol 11 ◽

Author(s):

Cheng-Ju Kuo ◽

Ya-Chu Hsu ◽

Sin-Tian Wang ◽

Bang-Yu Liou ◽

Serene Boon-Yuean Lim ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

P38 Mapk ◽

Mapk Pathway ◽

Transmembrane Protein ◽

Host Susceptibility ◽

Leucine Rich Repeat ◽

C Elegans ◽

P38 Mapk Pathway ◽

Immune Pathway ◽

Pathogen Avoidance

Enterohemorrhagic Escherichia coli (EHEC), a human pathogen, also infects Caenorhabditis elegans. We demonstrated previously that C. elegans activates the p38 MAPK innate immune pathway to defend against EHEC infection. However, whether a C. elegans pattern recognition receptor (PRR) exists to regulate the immune pathway remains unknown. PRRs identified in other metazoans contain several conserved domains, including the leucine-rich repeat (LRR). By screening a focused RNAi library, we identified the IGLR-2, a transmembrane protein containing the LRR domain, as a potential immune regulator in C. elegans. Our data showed that iglr-2 regulates the host susceptibility to EHEC infection. Moreover, iglr-2 is required for pathogen avoidance to EHEC. The iglr-2 overexpressed strain, which was more resistant to EHEC originally, showed hypersusceptibility to EHEC upon knockdown of the p38 MAPK pathway. Together, our data suggested that iglr-2 plays an important role in C. elegans to defend EHEC by regulating pathogen-avoidance behavior and the p38 MAPK pathway.

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Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction

Nature Communications ◽

10.1038/s41467-020-18690-4 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Manish Chamoli ◽

Anita Goyala ◽

Syed Shamsh Tabrez ◽

Atif Ahmed Siddiqui ◽

Anupama Singh ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Life Span ◽

P38 Mapk ◽

Dietary Restriction ◽

Mapk Pathway ◽

Metabolic Reprogramming ◽

Metabolic State ◽

P38 Mapk Pathway

Abstract The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of “Xenobiotic Detoxification Program” (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.

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