• Toxicological Research
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• v.28 no.1
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• pp.19-24
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• 2012

In the present study, toxicity of silver nanoparticles (AgNPs) was investigated in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway responsible for regulating oxidative stress, such as mitogen-activated protein kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed in AgNPs exposed C.elegans, suggesting oxidative stress as an important mechanism in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK signaling pathways increased by AgNPs exposure in less than 2-fold compared to the control in wildtype C.elegans, however, those were increased dramatically in sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk-2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on the expression of oxidative stress response genes suggest that sod-3 gene expression appears to be dependent on p38 MAPK activation. The high expressions of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be interpreted as compensatory mechanisms in the absence of important stress response genes. Overall results suggest that MAPK-based integrated stress signaling network seems to be involved in defense to AgNPs exposure in C.elegans.

• Journal of Plant Biotechnology
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• v.49 no.4
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• pp.300-306
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• 2022

The mitogen-activated protein kinase (MAPK) signaling cascade is essential for a wide range of cellular responses in plants, including defense responses, responses to abiotic stress, hormone signaling, and developmental processes. Recent investigations have shown that the stress, ethylene, and MAPK signaling pathways negatively affect the formation of nitrogen-fixing nodules by directly modulating the symbiotic signaling components. However, the molecular mechanisms underlying the defense responses mediated by MAPK signaling in the organogenesis of nitrogen-fixing nodules remain unclear. In the present study, I demonstrate that the Medicago truncatula mitogen-activated protein kinase kinase 5 (MtMKK5)-Medicago truncatula mitogen-activated protein kinase 3/6 (MtMPK3/6) signaling module, expressed specifically in the symbiotic nodules, promotes defense signaling, but not ethylene signaling pathways, thereby inhibiting nodule development in M. truncatula. U0126 treatment resulted in increased cell division in the nodule meristem zone due to the inhibition of MAPK signaling. The phosphorylated TEY motif in the activation domain of MtMPK3/6 was the target domain associated with specific interactions with MtMKK5. I have confirmed the physical interactions between M. truncatula nodule inception (MtNIN) and MtMPK3/6. In the presence of high expression levels of the defense-related genes FRK1 and WRKY29, MtMKK5a overexpression significantly enhanced the defense responses of Arabidopsis against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Overall, my data show that the negative regulation of symbiotic nitrogen-fixing nodule organogenesis by defense signaling pathways is mediated by the MtMKK5-MtMPK3/6 module.

• Molecules and Cells
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• v.40 no.10
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• pp.697-705
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• 2017

The maintenance of inorganic phosphate (Pi) homeostasis is essential for plant growth and yield. Plants have evolved strategies to cope with Pi starvation at the transcriptional, post-transcriptional, and post-translational levels, which maximizes its availability. Many transcription factors, miRNAs, and transporters participate in the Pi starvation signaling pathway where their activities are modulated by sugar and phytohormone signaling. Environmental stresses significantly affect the uptake and utilization of nutrients by plants, but their effects on the Pi starvation response remain unclear. Recently, we reported that Pi starvation signaling is affected by abiotic stresses such as salt, abscisic acid, and drought. In this review, we identified transcription factors, such as MYB, WRKY, and zinc finger transcription factors with functions in Pi starvation and other environmental stress signaling. In silico analysis of the promoter regions of Pi starvation-responsive genes, including phosphate transporters, microRNAs, and phosphate starvation-induced genes, suggest that their expression may be regulated by other environmental stresses, such as hormones, drought, cold, heat, and pathogens as well as by Pi starvation. Thus, we suggest the possibility of cross-talk between Pi starvation signaling and other environmental stress signaling pathways.

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.3
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• pp.212-221
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• 2019

Sestrin-2 (SESN2) as a stress-metabolic protein is known for its anti-oxidative effects as a downstream factor of PERK pathways in mammalian cells. However, the expression patterns of SESN2 in conjunction with the UPR signaling against to ER stress on porcine oocyte maturation in vitro, have not been reported. Therefore, we confirmed the expression pattern of SESN2 protein, for which to examine the relationship between PERK signaling and SESN2 in porcine oocyte during IVM. We investigated the SESN2 expression patterns using Western blot analysis in denuded oocytes (DOs), cumulus cells (CCs), and cumulus-oocyte complexes (COCs) at 22 and 44 h of IVM. As expected, the SESN2 protein level significantly increased (p < 0.01) in porcine COCs during 44 h of IVM. We investigated the meiotic maturation after applying ER stress inhibitor in various concentration (50, 100 and 200 μM) of tauroursodeoxycholic acid (TUDCA). We confirmed significant increase (p < 0.05) of meiotic maturation rate in TUDCA 200 μM treated COCs for 44 h of IVM. Finally, we confirmed the protein level of SESN2 and meiotic maturation via regulating ER-stress by only tunicamycin (Tm), only TUDCA, and Tm + TUDCA treatment in porcine COCs. As a result, treatment of the TUDCA following Tm pre-treatment reduced SESN2 protein level in porcine COCs. In addition, SESN2 protein level significantly reduced in only TUDCA treated porcine COCs. Our results suggest that the SESN2 expression is related to the stress mediator response to ER stress through the PERK signaling pathways in porcine oocyte maturation.

• Molecules and Cells
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• v.40 no.1
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• pp.17-23
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• 2017

Mitogen-activated protein kinase (MAPK) signaling cascades play critical roles in various cellular events in plants, including stress responses, innate immunity, hormone signaling, and cell specificity. MAPK-mediated stress signaling is also known to negatively regulate nitrogen-fixing symbiotic interactions, but the molecular mechanism of the MAPK signaling cascades underlying the symbiotic nodule development remains largely unknown. We show that the MtMKK5-MtMPK3/6 signaling module negatively regulates the early symbiotic nodule formation, probably upstream of ERN1 (ERF Required for Nodulation 1) and NSP1 (Nod factor Signaling Pathway 1) in Medicago truncatula. The overexpression of MtMKK5 stimulated stress and defense signaling pathways but also reduced nodule formation in M. truncatula roots. Conversely, a MAPK specific inhibitor, U0126, enhanced nodule formation and the expression of an early nodulation marker gene, MtNIN. We found that MtMKK5 directly activates MtMPK3/6 by phosphorylating the TEY motif within the activation loop and that the MtMPK3/6 proteins physically interact with the early nodulation-related transcription factors ERN1 and NSP1. These data suggest that the stress signaling-mediated MtMKK5/MtMPK3/6 module suppresses symbiotic nodule development via the action of early nodulation transcription factors.

• Journal of Microbiology and Biotechnology
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• v.34 no.5
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• pp.1059-1072
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• 2024

Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Salvia miltiorrhiza Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.

• BMB Reports
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• v.35 no.1
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• pp.24-27
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• 2002

Apoptotic cell death is an active process mediated by various signaling pathways, which include the caspase cascade and the stress-activated protein kinase pathways. The caspase cascade is activated by two distinct routes: one from cell surface and the other from mitochondria. Activation of the route from cell surface requires the cellular components that include membrane receptors, adaptor proteins such as TRADD and FADD, and caspase-8, while activation of the other from mitochondria requires Apaf-1, caspase-9, and cytosolic cytochrome c. On the other hand, persistent stimulation of the stress-activated protein kinase pathway is also shown to mediate apoptosis in many cell types. Gene-targeting studies with jnk- or jip-null mice, in particular, strongly suggest that this signaling pathway plays a pivotal role in the cellular machinery for apoptosis.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.33-39
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• 2016

Oxidative stress activates several intracellular signaling cascades that may have deleterious effects on neuronal cell survival. Thus, controlling oxidative stress has been suggested as an important strategy for prevention and/or treatment of neurodegenerative diseases. In this study, we found that ginsenoside Rh1 inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. Rh1 increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1, superoxide dismutase-2, and catalase, that are under the control of Nrf2/ARE signaling pathways. Further mechanistic studies showed that Rh1 increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to the antioxidant response element (ARE), and increased the ARE-mediated transcription activities in rat primary astrocytes. Analysis of signaling pathways revealed that MAP kinases are important in HO-1 expression, and act by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by Rh1 may provide preventive therapeutic potential for various neurodegenerative diseases that are associated with oxidative stress.

• BMB Reports
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• v.40 no.1
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• pp.1-6
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• 2007

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogenactivated protein kinase (MAPK) kinase kinase that activates JNK and p38 kinases. ASK1 is activated by various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx which are thought to be responsible for the pathogenesis or exacerbations of various human diseases. Recent studies revealed the involvement of ASK1 in ROS- or ER stressrelated diseases, suggesting that ASK1 may be a potential therapeutic target of various human diseases. In this review, we focus on the current findings for the relationship between pathogenesis and ASK1-MAPK pathways.

• Biomedical Science Letters
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• v.25 no.3
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• pp.211-217
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• 2019

Research has established a strong connection between a diet rich in antioxidants and a decreased incidence of cardiovascular disease and cancer. These diets prominently feature fruits and vegetables containing high amounts of vitamins A, B, C and E, carotenoids, and minerals. Different processing conditions for these foods can alter their nutrient complement and potency. This study compared the antioxidant properties of a range of processed fruits and vegetables to see which yielded the highest level of antioxidant activity. We used an acetaminophen-induced oxidative stress mouse model to evaluate the antioxidant effects of extracts of processed apple, pear, carrot, cabbage, broccoli, and radish. Our results showed that the administration of these fruits decreased the expression of oxidative stress indicators such as ALT, AST, catalase, superoxide dismutase, GPx, and 8-OHdG. They also significantly protected mice livers from APAP-induced damage, as shown by histological evaluation. Our results have demonstrated the positive effects of processed fruits and vegetables in a mouse model of oxidative stress.