signaling components
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Author(s):  
Chen-Yu Wang ◽  
Chien-Chung Yang ◽  
Li-Der Hsiao ◽  
Chuen-Mao Yang

AbstractExcessive production of reactive oxygen species (ROS) by NADPH oxidase (Nox) resulted in inflammation. The negative regulator of ROS (NRROS) dampens ROS generation during inflammatory responses. 15-Deoxy-∆12,14-prostaglandin J2 (15d-PGJ2) exhibits neuroprotective effects on central nervous system (CNS). However, whether 15d-PGJ2-induced NRROS expression was unknown in rat brain astrocytes (RBA-1). NRROS expression was determined by Western blot, RT/real-time PCR, and promoter activity assays. The signaling components were investigated using pharmacological inhibitors or specific siRNAs. The interaction between transcription factors and the NRROS promoter was investigated by chromatin immunoprecipitation assay. Upregulation of NRROS on the hydrogen peroxide (H2O2)-mediated ROS generation and interleukin 6 (IL-6) secretion was measured. 15d-PGJ2-induced NRROS expression was mediated through PI3K/Akt-dependent activation of Sp1 and FoxO1 and established the essential promoter regions. We demonstrated that 15d-PGJ2 activated PI3K/Akt and following by cooperation between phosphorylated nuclear FoxO1 and Sp1 to initiate the NRROS transcription. In addition, Nrf2 played a key role in NRROS expression induced by 15d-PGJ2 which was mediated through its phosphorylation. Finally, the NRROS stable clones attenuated the H2O2-induced ROS generation and expression of IL-6 through suppressing the Nox-2 activity. These results suggested that 15d-PGJ2-induced NRROS expression is mediated through a PI3K/Akt-dependent FoxO1 and Sp1 phosphorylation, and Nrf2 cascade, which suppresses ROS generation through attenuating the p47phox phosphorylation and gp91phox formation and IL-6 expression in RBA-1 cells. These results confirmed the mechanisms underlying 15d-PGJ2-induced NRROS expression which might be a potential strategy for prevention and management of brain inflammatory and neurodegenerative diseases.


2022 ◽  
Author(s):  
Deeksha Singh ◽  
Hiteshwari Singh ◽  
Nivedita Singh ◽  
Shambhavi Dwivedi ◽  
Prabodh Kumar Trivedi

Plants have evolved complex signaling networks to regulate their growth and development. Some of these signaling components also play a crucial role in secondary metabolite biosynthesis. Among the signaling components identified to date, ELONGATED HYPOCOTYL 5 (HY5), a bZIP family transcription factor is the most investigated and known as the center of transcriptional network hub. However, HY5 has not been characterized from plants known to synthesize important secondary metabolites. In this study, based on homology search and phylogenetic analysis, HY5 has been identified from Nicotiana tobaccum, and characterized for its role in secondary plant product biosynthesis and stress response through developing overexpressing lines and CRISPR/Cas9-based knockout mutant plants. NtHY5 was able to complement the Arabidopsis thaliana hy5 mutant at molecular, morphological and biochemical levels. Overexpression of NtHY5 in tobacco led to the up-regulation of the phenylpropanoid pathway genes and enhanced the flavonoid content, whereas mutant plants had the opposite effect. Electrophoretic Mobility Shift Assay (EMSA) suggested that NtHY5 interacts with the promoter of NtMYB12, a transcription factor known to regulate flavonoid biosynthesis. In addition, NtHY5 enhanced the abiotic stress tolerance as evident by the salt tolerance ability of HY5 overexpressing lines by diminishing the ROS accumulation after salt treatment. These data provide credible evidence about the potential role of NtHY5 in light-mediated flavonoid biosynthesis, plant growth and abiotic stress tolerance in tobacco. The photomorphogenic mutant, Nthy5, developed in this study, will help in elucidating the role of the HY5 in different biological processes in tobacco.


2022 ◽  
Vol 12 ◽  
Author(s):  
Victor P. Bulgakov ◽  
Olga G. Koren

It is generally accepted that plants use the complex signaling system regulated by light and abscisic acid (ABA) signaling components to optimize growth and development in different situations. The role of ABA–light interactions is evident in the coupling of stress defense reactions with seed germination and root development, maintaining of stem cell identity and stem cell specification, stem elongation and leaf development, flowering and fruit formation, senescence, and shade avoidance. All these processes are regulated jointly by the ABA–light signaling system. Although a lot of work has been devoted to ABA–light signal interactions, there is still no systematic description of central signaling components and protein modules, which jointly regulate plant development. New data have emerged to promote understanding of how ABA and light signals are integrated at the molecular level, representing an extensively growing area of research. This work is intended to fill existing gaps by using literature data combined with bioinformatics analysis.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Majid Gholipour ◽  
Soheyla Mazaheri

Background: Muscle loss occurs in some conditions such as aging, sarcopenia, and cancer. The interaction between protein synthesis and degradation signaling components induced by high-intensity interval training (HIIT) is not well studied. Objectives: The purpose of the present study was to simultaneously examine the effect of eight-week HIIT on the gene expression of both signaling components. Methods: Sixteen male Wistar rats were randomly assigned to HIIT and non-exercise control groups. The HIIT group ran on a treadmill, five days/week for eight weeks, with 0º slope, including five interval sets of high and low intensity. Forty-eight hours after the last exercise session, dissected soleus muscles were stored at -80°C for later analyses. Results: The gene expression of Akt1, mTORC1, and S6K1 were increased in the HIIT group compared with the control group (All P ≤ 0.031) concomitant with the suppression of eIF4EBP1. The results of the S6K1 and eIF4EBP1 mRNA were also confirmed by the Western blotting. According to the inhibitory effect of Akt1, the gene expressions of FoxO3a and, consequently, MuRF1 and LC3A were significantly inhibited (All P ≤ 0.003). Western blot analysis did not confirm the LC3A protein expression, which may underline the role of LC3A in autophagy to promote cell survival. Conclusions: The intensities and durations of the exercise training protocol are sufficient to increase protein synthesis signaling components and especially inhibit the atrophy-related gene expression, which may lead to attenuating muscle loss and increasing muscle mass. Accordingly, it may be considered for rehabilitation and/or prevention of some conditions such as sarcopenia and cachexia.


Author(s):  
Yifang Yan ◽  
Qiang Wang

One of the most significant events during early embryonic development is the establishment of a basic embryonic body plan, which is defined by anteroposterior, dorsoventral (DV), and left-right axes. It is well-known that the morphogen gradient created by BMP signaling activity is crucial for DV axis patterning across a diverse set of vertebrates. The regulation of BMP signaling during DV patterning has been strongly conserved across evolution. This is a remarkable regulatory and evolutionary feat, as the BMP gradient has been maintained despite the tremendous variation in embryonic size and shape across species. Interestingly, the embryonic DV axis exhibits robust stability, even in face of variations in BMP signaling. Multiple lines of genetic, molecular, and embryological evidence have suggested that numerous BMP signaling components and their attendant regulators act in concert to shape the developing DV axis. In this review, we summarize the current knowledge of the function and regulation of BMP signaling in DV patterning. Throughout, we focus specifically on popular model animals, such as Xenopus and zebrafish, highlighting the similarities and differences of the regulatory networks between species. We also review recent advances regarding the molecular nature of DV patterning, including the initiation of the DV axis, the formation of the BMP gradient, and the regulatory molecular mechanisms behind BMP signaling during the establishment of the DV axis. Collectively, this review will help clarify our current understanding of the molecular nature of DV axis formation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Huiying Xu ◽  
Peirui Chen ◽  
Yi Tao

Based on how plants respond to shade, we typically classify them into two groups: shade avoiding and shade tolerance plants. Under vegetative shade, the shade avoiding species induce a series of shade avoidance responses (SARs) to outgrow their competitors, while the shade tolerance species induce shade tolerance responses (STRs) to increase their survival rates under dense canopy. The molecular mechanism underlying the SARs has been extensively studied using the shade avoiding model plant Arabidopsis thaliana, while little is known about STRs. In Aarabidopsis, there is a PHYA-mediated negative feedback regulation that suppresses exaggerated SARs. Recent studies revealed that in shade tolerance Cardamine hirsuta plants, a hyperactive PHYA was responsible for suppressing shade-induced elongation growth. We propose that similar signaling components may be used by shade avoiding and shade tolerance plants, and different phenotypic outputs may result from differential regulation or altered dynamic properties of these signaling components. In this review, we summarized the role of PHYA and its downstream components in shade responses, which may provide insights into understanding how both types of plants respond to shade.


2021 ◽  
Vol 9 ◽  
Author(s):  
Haibao Zhang ◽  
Shan Xu ◽  
Dalin He ◽  
Xinyang Wang ◽  
Guodong Zhu

Objectives: Sonic hedgehog (SHH) signaling is important in bladder development. Mice with defective hedgehog signaling develop bladder anomalies. Clinically, urinary tract malformations are reported in human fetuses and infants with mutations of SHH and related signaling pathway genes. Information on the expression of SHH and associated signaling genes in normal human bladder development is fragmentary. This study determined the temporal and spatial expression patterns of SHH signaling pathway components in human fetal bladders by immunohistochemistry (IHC).Material and Methods: Twenty-four bladder specimens from 16 male and 8 female human fetuses aged 12- to 36-week (wk) were obtained from the First Affiliated Hospital of Xi'an Jiaotong University. The tissue slides were processed for IHC staining with SHH, Patched1 (PTC-1), Patched2 (PTC-2), Smoothened (SMO), GLI1 and proliferating cell nuclear antigen (PCNA). The expression levels of each gene were analyzed by semi-quantitative histological scoring system.Results: High intensity of SHH and SMO expression was detected in developing bladder urothelial cells, with no staining in lamina propria (LP), but with minimal expression of SMO in differentiating smooth muscle (SM) layers. The spatial distribution pattern of PTC1 and GLI1 was more complex with minimal expression in the LP layer, moderate expression in the SM layer, and high expression in the urothelium. PTC2 expression was mainly localized in the urothelium and LP, but no expression in the SM layer. All of the SHH signaling components were detected in fetal bladder tissues throughout the development, with expression peaks at 12- and 23-wk, coinciding with high cell proliferation as indicated by PCNA staining in the cell nuclei of urothelium and SM.Conclusions: The autocrine SHH signaling in the developing urothelium, and paracrine SHH signaling in the developing smooth muscle layer, mediated by SMO, PTC-1 and GLI1 were demonstrated during human bladder development. Expression of SHH signaling components peaked at 12-and 23-wk. The first expression peak at 12-wk may relate to urothelium growth, SM induction, and dilation of the bladder cavity. The second expression peaked at 23-wk may relate to urothelium and SM layer differentiation.


2021 ◽  
Author(s):  
Yiping Wang ◽  
Yingying Wu ◽  
Huan Zhong ◽  
Shuai Chen ◽  
Kam‐Bo Wong ◽  
...  
Keyword(s):  

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1609
Author(s):  
Hannah L. Norris ◽  
Rohitashw Kumar ◽  
Mira Edgerton

Candida albicans is maintained as a commensal by immune mechanisms at the oral epithelia. Oral antifungal peptide Histatin 5 (Hst 5) may function in innate immunity, but the specific role Hst 5 plays in C. albicans commensalism is unclear. Since Zn-binding potentiates the candidacidal activity of Hst 5, we hypothesized that Hst 5+Zn would elicit a unique fungal stress response to shape interactions between C. albicans and oral epithelial cells (OECs). We found that Hst 5+Zn but not Hst 5 alone resulted in the activation of cell wall integrity (CWI) signaling, and deletion mutants were then used to determine that CWI-mediated chitin synthesis was protective against killing. Using flow cytometry, we confirmed that Hst 5+Zn-treated cells had significantly elevated levels of cell-wall chitin, mannan and β-1,3 glucan compared to Hst 5-treated cells. We then tested the activation of host signaling components involved in C. albicans cell-wall recognition. The immunoblot assay of C. albicans-exposed oral epithelial cells showed increased activation of EphA2 and NF-κB but not EGFR. Interestingly, C. albicans treated with Hst 5+Zn induced the global suppression of pro-inflammatory cytokine release from OECs, but an increase in negative regulator IL-10. Hst 5+Zn-treated cells were more adherent but ultimately less invasive to OECs than control cells, thus indicating lowered virulence. Therefore, Hst 5+Zn-treated C. albicans cells are discerned by epithelial monolayers, but are less virulent and promote anti-inflammatory signaling, suggesting that Hst 5+Zn in combination could play a role in regulating commensalism of oral C. albicans through cell wall reorganization.


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