Seung-On Lee, Sang Hoon Joo, Jisu Park, Quan T Khong, Si Yeong Seo, Goo Yoon, Jin Woo Park, MinKyun Na, Jung-Hyun Shim
{"title":"Deoxybouvardin Glucoside Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells via Reactive Oxygen Species-Mediated Activation of JNK and p38 MAPK.","authors":"Seung-On Lee, Sang Hoon Joo, Jisu Park, Quan T Khong, Si Yeong Seo, Goo Yoon, Jin Woo Park, MinKyun Na, Jung-Hyun Shim","doi":"10.4014/jmb.2410.10008","DOIUrl":"10.4014/jmb.2410.10008","url":null,"abstract":"<p><p>The roots of <i>Rubia</i> spp. (Rubiaceae) have been employed to treat hematemesis, inflammatory disease, and tumor. Cyclohexapeptides derived from <i>Rubia</i> spp. have been reported to have antitumor potential; however, the mechanism of action for their antitumor activity remains unclear. We aimed to examine the antitumor effect of deoxybouvardin glucoside (DBG), a cyclohexapeptide from <i>Rubia</i> spp. on oxaliplatin (Ox)-resistant human HCT116 colorectal cancer (CRC) cells. Cell viability in the presence of DBG was monitored using an MTT viability assay, and flow cytometry was used to analyze changes in apoptosis, cell cycle, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) activity. The antiproliferative activity involved apoptosis and phosphorylation of JNK and p38 MAPK. Inhibition of JNK and p38 MAPK by specific inhibitors prevented DBG-induced apoptosis, underscoring the close involvement of these kinases. Further, DBG induced cell cycle arrest in CRC cells at the G2/M phase by regulating the p21, p27, cyclin B1, and cdc2 proteins. DBG-induced apoptosis was accompanied mitochondrial membrane depolarization, resulting in cytochrome c release into the cytoplasm and caspase activation. Remarkably, DBG induced apoptosis by generating high ROS levels. The mediation of apoptosis by increased ROS generation was confirmed by pretreatment with the ROS scavenger N-acetyl cysteine (NAC). Collectively, DBG exhibited anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting JNK and p38 MAPK, inducing cell cycle arrest, elevating cellular ROS levels, and disrupting MMP. This study suggests that DBG has the potential to be utilized as a therapeutic agent for treating Ox-resistant CRC.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"e2410008"},"PeriodicalIF":2.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye-Rin Ju, Su Been Im, Da Eun Jung, Min Jeong Son, Chan-Young Park, Min Ho Jeon, Ju Hee Hwang, Soo Jung Lee, Tae-Jip Kim
{"title":"Exo- and Endo-1,5-α-L-Arabinanases and Prebiotic Arabino-Oligosaccharides Production.","authors":"Ye-Rin Ju, Su Been Im, Da Eun Jung, Min Jeong Son, Chan-Young Park, Min Ho Jeon, Ju Hee Hwang, Soo Jung Lee, Tae-Jip Kim","doi":"10.4014/jmb.2412.12052","DOIUrl":"10.4014/jmb.2412.12052","url":null,"abstract":"<p><p>There is growing interest in pentose-based prebiotic oligosaccharides as alternatives to traditional hexose-based prebiotics. Among these, arabino-oligosaccharides (AOS), derived from the enzymatic hydrolysis of arabinan polymers, have gained significant attention. AOS can selectively stimulate the growth of beneficial gut bacteria, including <i>Bifidobacterium</i> and <i>Bacteroides</i> species, and contribute to health-benefit functions such as blood sugar control, positioning AOS as a promising synbiotic candidate. For the industrial production of AOS, the development of efficient enzymatic processes is essential, with exo- and endo-1,5-α-L-arabinanases (exo- and endo-ABNs) playing a crucial catalytic role. Most ABNs belong to the glycoside hydrolase (GH) family 43, characterized by a five-bladed β-propeller fold structure. These enzymes hydrolyze internal α-1,5-L-arabinofuranosidic linkages, producing AOS with varying degrees of polymerization. Some ABNs GH43 were known to exhibit exo-type hydrolytic modes of action, producing specific AOS products such as arabinotriose. Additionally, exo-ABNs from GH93, which feature a six-bladed β-propeller fold, exclusively release arabinobiose through their exo-type catalytic mechanism. This review represents the first comprehensive analysis of exo- and endo-ABNs, offering scientific insights into their biotechnological potential for AOS production. It systematically compares enzyme classification, structural differences, catalytic mechanisms, paving the way for innovative applications in health, food, and pharmaceutical industries.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"e2412052"},"PeriodicalIF":2.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Byeong Min Choi, Tae-Jin Park, HuSang Harry Lee, Hyehyun Hong, Won-Jae Chi, Seung-Young Kim
{"title":"Inhibition of Melanin Synthesis and Inflammation by Exosomes Derived from <i>Leuconostoc mesenteroides</i> DB-14 Isolated from <i>Camellia japonica</i> Flower.","authors":"Byeong Min Choi, Tae-Jin Park, HuSang Harry Lee, Hyehyun Hong, Won-Jae Chi, Seung-Young Kim","doi":"10.4014/jmb.2411.11080","DOIUrl":"10.4014/jmb.2411.11080","url":null,"abstract":"<p><p><i>Leuconostoc mesenteroides</i> is a lactic acid bacteria found in fermented products. In our previous study, <i>L. mesenteroides</i> was isolated from <i>Camellia japonica</i> flowers, and its acid tolerance and antibacterial properties were thoroughly investigated. This study focuses on the inhibition of melanin synthesis and inflammation of exosomes derived from <i>L. mesenteroides</i>. Moreover, <i>L. mesenteroides</i> exosomes (DB-14 exosome) exhibited significant inhibitory effects on inflammation and melanogenesis. At concentrations of 4.44 × 10<sup>8</sup>, 8.88 × 10<sup>8</sup>, and 1.78 × 10<sup>9</sup> particles/ml, the exosomes reduced nitric oxide and prostaglandin E2 activity while maintaining the growth of RAW 264.7 macrophages. In addition, proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha, were rarely expressed, and western blot revealed that <i>L. mesenteroides</i> DB-14 derived exosomes inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, the exosomes had no toxic effects on B16F10 melanoma cells at concentrations of 1.78 × 10<sup>9</sup>, 3.55 × 10<sup>9</sup>, and 7.10 × 10<sup>9</sup> particles/ml, and they suppressed melanogenesis by reducing tyrosinase activity. Furthermore, western blot analysis demonstrated that microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 were evidently reduced, ultimately repressing melanin production. Moreover, MITF expression was inhibited by reduced mitogen-activated protein kinase and protein kinase B phosphorylation levels. Overall, this study proves the efficacy of the novel DB-14 exosome as a strong lightening and anti-inflammatory agent.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"e2411080"},"PeriodicalIF":2.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Loss in Pluripotency Markers in Mesenchymal Stem Cells upon Infection with <i>Chlamydia trachomatis</i>.","authors":"Munir A Al-Zeer, Mohammad Abu Lubad","doi":"10.4014/jmb.2406.06023","DOIUrl":"10.4014/jmb.2406.06023","url":null,"abstract":"<p><p>The intracellular pathogen <i>Chlamydia trachomatis</i> can inflict substantial damage on the host. Notably, Chlamydia infection is acknowledged for its precise modulation of diverse host signaling pathways to ensure cell survival, a phenomenon intricately connected to genetic regulatory changes in host cells. To monitor shifts in gene regulation within Chlamydia-infected cells, we employed mesenchymal stem cells (MSCs) as a naïve, primary cell model. Utilizing biochemical methods and imaging, our study discloses that acute Chlamydia infection in human MSCs leads to the downregulation of transcription factors Oct4, Sox2, and Nanog, suggesting a loss of pluripotency markers. Conversely, pluripotency markers in MSCs were sustained through treatment with conditioned medium from infected MSCs. Additionally, there is an augmentation in alkaline phosphatase activity, along with elevated Sox9 and CD44 mRNA expression levels observed during acute infection. A comprehensive screening for specific cell markers using touchdown PCR indicates an upregulation of mRNA for the early chondrogenesis gene Sox9 and a decrease in mRNA for the MSC marker vimentin. Real-time PCR quantification further corroborates alterations in gene expression, encompassing increased Sox9 and CD44 mRNA levels, alongside heightened alkaline phosphatase activity. In summary, the infection of MSCs with <i>C. trachomatis</i> induces numerous genetic deregulations, implying a potential trend towards differentiation into chondrocytes. These findings collectively underscore a targeted impact of Chlamydia on the gene regulations of host cells, carrying significant implications for the final fate and differentiation of these cells.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2465-2473"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Triple-Branch Catalytic Assembly DNAzyme Motivated DNA Tweezer for Sensitive and Reliable <i>mecA</i> Gene Detection in <i>Staphylococcus aureus</i>.","authors":"Xiaoyang Li, Meiyan Xu, Fangmin Gan, Hui Zhao","doi":"10.4014/jmb.2409.09008","DOIUrl":"10.4014/jmb.2409.09008","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> (<i>S. aureus</i>, SA) is one of the most common bacteria in nosocomial infections. Sensitive and efficient analysis of methicillin-resistance of SA is crucial for improving the nursing performance of pneumonia. However, methicillin-resistance analysis with favorable sensitivity and specificity in an enzyme-free manner remains a huge challenge. This paper presents the development of a new fluorescent biosensor for detecting <i>mecA</i> gene using a triple-branch catalytic hairpin assembly (CHA) triggered DNAzyme switch-based DNA tweezer. The SA from the samples are immobilized on the plate's surface using the protein A antibody. The biosensor possesses several key features. Firstly, it utilizes dual signal amplification processes, specifically the triple-branch CHA and DNAzyme controlled DNA tweezer-based signal recycling, to enable <i>mecA</i> detection on the plate. This design enhances the method's sensitivity, resulting in a low limit of detection of 1.5 fM. Secondly, the biosensor does not rely on enzymes for <i>mecA</i> analysis, ensuring a high level of stability during target analysis. Lastly, the method demonstrates a remarkable selectivity by accurately distinguishing target sequences from non-target sequences. The proposed biosensor, which does not require enzymes and has a high level of sensitivity, offers a viable platform for the rapid and simple quantification of <i>mecA</i> in SA.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2450-2456"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Icariside II Preparation from Icariin Separated from <i>Epimedium</i> Herbal Extract Powder by a Special Icariin Glycosidase.","authors":"Xinyu Liu, Siyu Xu, Chunying Liu, Zhenghao Wang, Bo Wu, Meijuan Guo, Changkai Sun, Hongshan Yu","doi":"10.4014/jmb.2408.08046","DOIUrl":"10.4014/jmb.2408.08046","url":null,"abstract":"<p><p>In this study, icariside II was prepared from icariin by a special enzyme. The yield of the substrate icariin from a powdered extract of the popular herb <i>Epimedium</i> was 16.9%. The enzyme, which was produced from <i>Aspergillus</i> sp.y48 fermentation, hydrolyzes icariin to icariside II and was characterized. The molecular weight was 75 kDa, while the optimum temperature and pH were 45°C and 5.0. The purified enzyme hydrolyzed the 7-<i>O</i>-glucoside of icariin or epimedin A, B, and C to icariside II, or sagittatoside A, B, and C, respectively, and further hydrolyzed the terminal 3-<i>O</i>-xyloside of sagittatoside B to icariside II. The enzyme is a special icariin glycosidase that hydrolyzed icariin to icariside II at low cost. Based on the crude enzyme's reaction dynamics, the optimal conditions for icariside II preparation showed that 2% icariin reacted at 45°C for 6 to 9 h. Here, we obtained 13.3 g icariside II and 0.45 g of the by-product icaritin from 20 g icariin. The icariside II molar yield was 87.4%, the by-product icaritin yield was 4.1%, and the total molar yield was 91.5%. Therefore, icariside II was resoundingly prepared from an icariin glycosidase of an <i>Epimedium</i> extract using a non-GMO, crude enzyme from <i>Aspergillus</i> sp.y48. The obtained icariside II and the by-product icaritin can be directly applied in the production of cosmetics and pharmaceuticals.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2683-2692"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibitory Effects of Cryptotanshinone and Dihydrotanshinone I on Intracellular Trafficking of Viral Glycoproteins.","authors":"Makoto Muroi, Dong-Sun Lee","doi":"10.4014/jmb.2409.09050","DOIUrl":"10.4014/jmb.2409.09050","url":null,"abstract":"<p><p>Antiviral agents that target the viral envelope surface glycoproteins can disrupt the interactions between the viral glycoproteins and host cell receptors, thereby preventing viral entry into host cells. However, the mechanisms underlying glycoprotein processing and cellular trafficking have not been fully elucidated. In this study, we aimed to investigate the mechanism of action of cryptotanshinone (CTN) and dihydrotanshinone I (DTN) as inhibitors of viral glycoprotein trafficking, by assessing their inhibitory action on syncytium formation and cytopathic effects. CTN and DTN were isolated and characterized from <i>Salvia miltiorrhiza</i>; they effectively inhibited syncytium formation in Newcastle disease virus-infected baby hamster kidney cells. Both compounds inhibited the transport of viral G-proteins to the cell surface, resulting in intracellular accumulation. These results suggest that CTN and DTN are potential glycoprotein trafficking inhibitors that function at the Golgi apparatus. Overall, our results indicate that CTN and DTN suppress intracellular glycosylation by competing as inhibitors of glycosylation trafficking.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2457-2464"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yea-Lim Lee, Ji-Yun Lee, Joo-Woong Park, Jin Lee, Hyun-Hoo Lee, Dae-Hee Lee
{"title":"Protective Effects of <i>Codium fragile</i> Extract against Acetaminophen-Induced Liver Injury.","authors":"Yea-Lim Lee, Ji-Yun Lee, Joo-Woong Park, Jin Lee, Hyun-Hoo Lee, Dae-Hee Lee","doi":"10.4014/jmb.2409.09061","DOIUrl":"10.4014/jmb.2409.09061","url":null,"abstract":"<p><p>Acetaminophen (APAP) is a well-known analgesic used globally. Generally, APAP has been proven to be safe and effective at therapeutic doses; however, it can cause serious liver damage when administered at high levels. We prepared <i>Codium fragile</i> extract (CFE) using the seaweed <i>C. fragile</i> and confirmed that the CFE contains a substance called Loliolide with antioxidant activity. We performed the present study to determine whether CFE protects HEPG2 cells and BALB/c mice from oxidative stress-induced liver damage. We confirmed that CFE and Loliolide were non-cytotoxic and protected against liver damage by reducing the activities of ALT and AST, which were increased by APAP treatment, and that CFE reduced the mRNA expression of inflammatory cytokines TNF-α and IL-6 and inhibited the phosphorylation of ERK and p38 in HEPG2 cells as determined by RT-PCR and Western blot analyses. Furthermore, the TNF-α and IL-6 levels, which were increased after APAP treatment in BALB/c mice, decreased after CFE treatment. Therefore, we demonstrated that CFE exerts a protective effect against APAP-induced liver injury by suppressing the inflammatory response through anti-inflammatory activity. Our findings provide new perspectives for developing functional foods that utilize seaweeds to improve liver function.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2675-2862"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heesoon Park, Kiyoon Kim, Denver I Walitang, Riyaz Sayyed, Tongmin Sa
{"title":"Shifts in Soil Bacterial Community Composition of Jujube Orchard Influenced by Organic Fertilizer Amendment.","authors":"Heesoon Park, Kiyoon Kim, Denver I Walitang, Riyaz Sayyed, Tongmin Sa","doi":"10.4014/jmb.2406.06037","DOIUrl":"10.4014/jmb.2406.06037","url":null,"abstract":"<p><p>Organic fertilizer application in agricultural land is known to improve soil microbial processes, fertility, and yield. In particular, the changes in soil chemical composition due to multi-year application of organic fertilizers are thought to alter the microbial community. Here, the effects of organic fertilization with oil-cake amendments (OC) on soil bacterial diversity, community profile, and enzyme activity were evaluated and compared to those amended with chemical fertilizer (NPK). Diversity indices show that the application of organic fertilizer potentially increases microbial diversity as well as the number of different microbial groups. The ordination plot distinguished and clustered both treatments, showing the differential effects of soil chemical factors on the microbial communities in each treatment. Proteobacteria, Verrucomicrobia, and Bacteriodetes were significantly more abundant in OC-amended soil than in the NPK soil, indicating alterations in community structure, composition, and diversity, concurrent to the changes in the pH, Ca, and Mg contents of the soil. These shifts in bacterial community structure and composition, partially explained by differences in soil chemical factors, could be observed from the phylum to the genus level in NPK- and OC-amended soils. The OC soil contained a significantly higher abundance of predicted genes corresponding to enzymes related to biogeochemical cycling, decomposition, and plant growth promotion. Collectively, these results support the use of an unconventional organic fertilizer positively altering bacterial populations in jujube orchards. The application of an unconventional organic fertilizer improved microbial diversity and enhanced ecosystem functions related to biogeochemical cycles, mineralization, and plant growth promotion.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"34 12","pages":"2539-2546"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seo Young Park, Yu-Jin Jeong, Kyung-Soo Lee, Jun-Young Park, Jongsun Park, Vernon L Tesh, Moo-Seung Lee
{"title":"Shiga Toxins Produced by Enterohaemorrhagic <i>Escherichia coli</i> Induce Inflammation in Toxin-Sensitive Cells through the p38 MAPK/MK2/Tristetraprolin Signaling Pathway.","authors":"Seo Young Park, Yu-Jin Jeong, Kyung-Soo Lee, Jun-Young Park, Jongsun Park, Vernon L Tesh, Moo-Seung Lee","doi":"10.4014/jmb.2410.10016","DOIUrl":"10.4014/jmb.2410.10016","url":null,"abstract":"<p><p>Shiga toxins (Stxs), produced by <i>Shigella dysenteriae</i> serotype 1 and certain <i>Escherichia coli</i> pathotypes, cause hemorrhagic colitis, which can progress to hemolytic uremic syndrome (HUS) and central nervous system (CNS) pathology. The underlying mechanisms of toxin-induced inflammation remain unclear. The p38 mitogen-activated protein kinase (MAPK) and its downstream target, MAPKAPK2 (MK2), play key roles in various cellular responses. We identified Tristetraprolin (TTP) as a novel substrate of MK2 in Stx-intoxicated cells. Western blot analysis showed that Stxs induce phosphorylation of MK2 (Thr334) and TTP in globotriaosylceramide (Gb<sub>3</sub>)-positive cells, including D-THP-1 macrophage-like cells and HK-2 renal epithelial cells, but not in Gb<sub>3</sub>-negative T84 colon carcinoma cells. After treatment with wild-type Stx, the activity of phosphorylated MK2 and TTP persists for up to 8 h, while Stx2a<sup>mut</sup>, which lacks N-glycosidase activity, causes transient MK2/TTP phosphorylation. This suggests that Stxs selectively mediate MK2 and TTP activation in a Gb<sub>3</sub>-dependent manner. Knockdown of TTP in Stx2a-treated D-THP-1 cells upregulates proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8, MCP-1, and MIP-1α. The MK2 inhibitor PF-3644022 significantly reduces TTP phosphorylation and blocks the production of IL-6, IL-8, MCP-1, and MIP-1α in Stx2a-stimulated HK-2 cells. In conclusion, the MK2-TTP signaling pathway regulates the inflammatory response induced by Stxs in toxin-sensitive cells.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"2439-2449"},"PeriodicalIF":2.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}