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NAD+ deficiency plays essential roles in the hyperuricemia of stroke-prone spontaneously hypertensive rat via xanthine dehydrogenase to xanthine oxidase conversion.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-12 DOI: 10.1016/j.bbrc.2024.151136
Sara Amelia Ferdaus, Hiroki Ohara, Hiroyuki Matsuo, Kohei Kawakami, Fumihiko Takeuchi, Koichi Fujikawa, Emi Kawakita, Norihiro Kato, Toru Nabika, Keizo Kanasaki
{"title":"NAD<sup>+</sup> deficiency plays essential roles in the hyperuricemia of stroke-prone spontaneously hypertensive rat via xanthine dehydrogenase to xanthine oxidase conversion.","authors":"Sara Amelia Ferdaus, Hiroki Ohara, Hiroyuki Matsuo, Kohei Kawakami, Fumihiko Takeuchi, Koichi Fujikawa, Emi Kawakita, Norihiro Kato, Toru Nabika, Keizo Kanasaki","doi":"10.1016/j.bbrc.2024.151136","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151136","url":null,"abstract":"<p><p>Inhibition of xanthine oxidoreductase (XOR) was shown to ameliorate the stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), suggesting hyperuricemia had a pathological role in this rat model. In this study, we thus aimed to explore mechanisms inducing hyperuricemia in SHRSP. XOR is known to have two forms, xanthine dehydrogenase (XDH) as the prototype and xanthine oxidase (XO) as the converted form through cleavage of a peptide bond or through formation of disulfide bonds in the enzyme. XO was shown to have a greater activity to produce UA and oxidative stress. We thus hypothesized that the excess conversion to XO caused the higher UA level in SHRSP. Male SHRSP at 10 weeks of age showed a higher serum level of UA and a higher activity of XO than those in Wistar-Kyoto rat. As the protein level of the total XOR did not differ between the two strains, the conversion to XO seemed responsible for the high UA level in SHRSP. Meanwhile, NAD<sup>+</sup> level in SHRSP was lower than that in WKY, suggesting that low NAD<sup>+</sup> promoted the conversion to XO in this strain. ß-nicotinamide mononucleotide (NMN) supplementation for 2 weeks increased NAD<sup>+</sup> level and reduced the serum UA level as well as the XO activity in SHRSP. These observations supported that a low NAD<sup>+</sup> accelerated the conversion of XDH to XO in SHRSP, which resulted in high UA. The current study suggested the potential significance of NMN supplementation in the treatment of hyperuricemia in humans.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151136"},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hormonal mechanisms in the paraventricular nuclei associated with hyperalgesia in Parkinson's disease model rats.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-12 DOI: 10.1016/j.bbrc.2024.151178
Shengsen Yang, Nayuka Usami, Shiou Ling Lu, Wakana Oda, Hiroharu Maegawa, Hitoshi Niwa, Chiho Kudo
{"title":"Hormonal mechanisms in the paraventricular nuclei associated with hyperalgesia in Parkinson's disease model rats.","authors":"Shengsen Yang, Nayuka Usami, Shiou Ling Lu, Wakana Oda, Hiroharu Maegawa, Hitoshi Niwa, Chiho Kudo","doi":"10.1016/j.bbrc.2024.151178","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151178","url":null,"abstract":"<p><p>Pain is a major non-motor symptom of Parkinson's disease (PD). The relationship between hyperalgesia and neuropeptides originating from paraventricular nucleus (PVN) in 6-hydroxydopamine (6-OHDA) rats has already been investigated for oxytocin (OXT), but not yet for arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). The present study aimed to investigate the alterations in these neuropeptides following nociceptive stimulation in PD model rats and to examine the mechanisms of hyperalgesia. Dopaminergic nigrostriatal lesions were induced by injecting 6-OHDA into the medial forebrain bundle. Subcutaneous formalin injection into the vibrissa pad was performed in rats as a nociceptive stimulus in the orofacial region. Dopamine depletion's effect on nociception was assessed by counting the p-ERK-immunoreactive (-IR) cells in the trigeminal spinal subnucleus caudalis (Vc). The PD model rats induced by 6-OHDA injection (6-OHDA rats) showed a significantly higher number of p-ERK-IR cells in the Vc than the sham rats, confirming hyperalgesia in 6-OHDA rats. Then, we investigated the immunohistochemical responses to OXT, AVP, and CRH cells in the PVN and examined the changes in blood levels of these neuropeptides. As a result, formalin injection increased neuronal activity and blood levels of OXT and CRH in sham rats, but these were suppressed in the 6-OHDA rats. Contrarily, neuronal activity and blood level of AVP were unaffected by nociceptive stimuli and were significantly lower in 6-OHDA rats than in sham rats. Our findings suggest that OXT and CRH suppression is linked to hyperalgesia in PD, whereas AVP does not directly influence the observed hyperalgesia.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151178"},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of osmotic pressure on membrane permeation through antimicrobial peptide-induced pores. 渗透压对抗菌肽诱导孔膜渗透的影响
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-12 DOI: 10.1016/j.bbrc.2024.151180
Marzuk Ahmed, Md Masum Billah, Masahito Yamazaki
{"title":"Effect of osmotic pressure on membrane permeation through antimicrobial peptide-induced pores.","authors":"Marzuk Ahmed, Md Masum Billah, Masahito Yamazaki","doi":"10.1016/j.bbrc.2024.151180","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151180","url":null,"abstract":"<p><p>Most antimicrobial peptides (AMPs) induce membrane damage such as pore formation in bacterial cells, resulting in rapid cell death. On the other hand, bacterial cells have a large intracellular turgor pressure, i.e., an osmotic pressure (Π) due to higher osmolarity inside bacterial cells, but the effects of Π on the membrane permeation of the internal contents of lipid vesicles and cells through AMP-induced pores are unknown. Here, we investigated the effect of Π on the membrane permeability of a water-soluble fluorescent probe, AlexaFluor 488 hydrazide (AF488), when passing through peptidyl-glycylleucine-carboxyamide (PGLa)- or magainin 2 (Mag)-induced nanopores in giant unilamellar vesicles (GUVs). For the interaction of PGLa with single GUVs under Π, the onset of pore formation was followed by a gradual increase in the membrane permeability coefficient, M<sub>P</sub>, until M<sub>P</sub> reached a steady value, P<sup>s</sup>. On the other hand, for the interaction of Mag with single GUVs under Π, the onset of pore formation was rapidly followed by a change of M<sub>P</sub> to P<sup>s</sup>. Small Π values enhanced the P<sup>s</sup> values of AF488 passing through the PGLa- or Mag-induced nanopores. The mechanisms underlying the increase of P<sup>s</sup> at small Π values were discussed. Based on these results and our previous results that the membrane tension (due to Π) enhances rate of AMP-induced pore formation, we consider the role of turgor pressure in AMP-induced damage in bacterial membranes and the efflux of internal contents.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151180"},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pre-ribosomal WDR74 module coordinates the early and late pre-rRNA processing stages for the NVL2-mediated regulation of 60S ribosome biogenesis.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-12 DOI: 10.1016/j.bbrc.2024.151175
Yuya Hirooka, Keiichi Izumikawa, Sotaro Miyao, Takayuki Ohga, Yuko Nobe, Masato Taoka, Masami Nagahama
{"title":"Pre-ribosomal WDR74 module coordinates the early and late pre-rRNA processing stages for the NVL2-mediated regulation of 60S ribosome biogenesis.","authors":"Yuya Hirooka, Keiichi Izumikawa, Sotaro Miyao, Takayuki Ohga, Yuko Nobe, Masato Taoka, Masami Nagahama","doi":"10.1016/j.bbrc.2024.151175","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151175","url":null,"abstract":"<p><p>WD repeat domain 74 (WDR74) is a nucleolar protein involved in the early stages of pre-60S maturation in the ribosome biogenesis pathway. In later stages, WDR74 interacts with MTR4, an RNA helicase that functions with the exosome nuclease complex, and is dissociated upon ATP hydrolysis by the chaperone-like nuclear VCP-like 2 (NVL2) AAA-ATPase. We previously reported that ATP hydrolysis-defective NVL2 causes aberrant accumulation of WDR74 on the MTR4-exosome complex at the nucleolar periphery and in the nucleoplasm and that this nuclear redistribution of WDR74 leads to the unusual cleavage of the early rRNA precursor within the internal transcribed spacer 1 sequence. However, the precise mechanisms underlying this NVL2-mediated regulation is largely obscure. In this study, co-immunoprecipitation combined with mass spectrometry revealed that WDR74 functions as part of a pre-ribosomal subcomplex, termed the WDR74 module, consisting of eukaryotic conserved WDR74, RPF1, MAK16, and RRP1. Each component of the WDR74 module was mutually essential for the interaction of other members with MTR4, and all components were required for the accurate cleavage of pre-rRNA during 60S ribosome biogenesis. Moreover, impaired release of WDR74 from the MTR4-exosome complex caused by NVL2 dysfunction prevented MTR4 from recruiting PICT1, an MTR4 adaptor protein required for the 3'-end maturation of 5.8S rRNA. Our results highlight the key role of the WDR74 module in coordinating the early pre-rRNA cleavage and late processing of pre-5.8S rRNAs.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151175"},"PeriodicalIF":2.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NSC-3852 synergistically enhances the cytotoxicity of olaparib in oral squamous cell carcinoma.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-11 DOI: 10.1016/j.bbrc.2024.151166
Yuka Sasaki, Takuma Inouchi, Chie Kise, Ryusuke Nakatsuka, Amane Inoue, Mitsuko Masutani, Tadashige Nozaki
{"title":"NSC-3852 synergistically enhances the cytotoxicity of olaparib in oral squamous cell carcinoma.","authors":"Yuka Sasaki, Takuma Inouchi, Chie Kise, Ryusuke Nakatsuka, Amane Inoue, Mitsuko Masutani, Tadashige Nozaki","doi":"10.1016/j.bbrc.2024.151166","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151166","url":null,"abstract":"<p><p>The PARP inhibitor olaparib is an anti-cancer agent based on synthetic lethality that targets poly (ADP-ribose) polymerases. It is used as a therapeutic agent for breast, ovarian, pancreatic, and prostate cancers carrying BRCA1/2 mutations that cause deficiency in homologous recombination. In recent years, acquired resistance to PARP inhibitors has become a clinical problem in PARP inhibitor-treated patients. Meanwhile, the development of molecular targeted drugs for highly malignant oral cancers has not progressed, and effective treatment strategies are needed. In this study, we identified the histone deacetylase inhibitor NSC-3852 as a compound that synergistically enhances the effects of olaparib in oral squamous cell carcinoma cell lines. N-Acetyl-l-cysteine treatment partially recovered cell survival after co-treatment with olaparib and NSC-3852. Moreover, the combination of olaparib and NSC-3852 rapidly upregulated γH2AX at 2 h after treatment, and induced S-phase arrest and apoptosis at 24 h after treatment, suggesting that this combination induced apoptosis through accumulation of massive DNA damage. Taken together, these findings demonstrate that NSC-3852 is a sensitizer of olaparib and suggest that the combination of NSC-3852 and olaparib may be a useful therapeutic strategy for homologous recombination-proficient cancers, including cancers with acquired resistance to olaparib and high-grade oral squamous cell carcinoma.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151166"},"PeriodicalIF":2.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Isoquercitrin improves diabetes nephropathy by inhibiting the sodium-glucose co-transporter-2 pathway.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-06 DOI: 10.1016/j.bbrc.2024.151142
Wenjie Zhang, Yongxiang Zhang, Wenshan Lv, Zili Kong, Fang Wang, Yangang Wang
{"title":"Isoquercitrin improves diabetes nephropathy by inhibiting the sodium-glucose co-transporter-2 pathway.","authors":"Wenjie Zhang, Yongxiang Zhang, Wenshan Lv, Zili Kong, Fang Wang, Yangang Wang","doi":"10.1016/j.bbrc.2024.151142","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151142","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is one of the most severe kidney complications and the primary contributor to end-stage renal disease on a global scale. It exacerbates the morbidity, mortality, and financial burden for individuals with diabetes. Isoquercitrin, a natural compound found in various plants, has demonstrated potential as an antidiabetic agent. However, it remains uncertain whether isoquercitrin exerts a protective effect on DN. Therefore, the objective of this study was to explore whether isoquercitrin confers a protective effect on DN and its potential mechanism. In vivo, a mouse model of DN induced by streptozotocin was established in the study. The hypoglycemic effect of isoquercitrin was assessed by measuring fasting blood glucose levels, insulin tolerance tests, and glucose tolerance test in animals. Urinary albumin creatinine ratio, serum lipid levels, and pathological changes in renal tissues were measured to evaluate the protective effect of isoquercitrin against DN. The expression of Sodium glucose co-transporter-2(SGLT2) was analyzed using real-time quantitative PCR and immunohistochemistry. The studies suggest that isoquercitrin significantly reduces fasting blood glucose levels, enhances the body's capacity to regulate blood glucose and insulin resistance, and facilitates renal pathology and renal function. Simultaneously, it can lower blood lipids (total cholesterol and triglyceride) and improve the risk factors of DN. Meanwhile, isoquercitrin suppressed the expression of SGLT2 in renal tissues of DN mouse models. In vitro, real-time quantitative PCR and Western blot were used to detect the expression of SGLT2 in the human renal tubular epithelial (HK-2) cells. The effects of isoquercitrin on the survival rate and glucose uptake capacity of HK-2 cells were determined by Cell-Counting-Kit-8 and glucose uptake methods. The results demonstrate that isoquercitrin suppressed the up-regulation of SGLT2 mRNA and protein in high-glucose-induced HK-2 cells. Additionally, isoquercitrin inhibited glucose uptake in HK-2 cells and mitigated high-sugar-induced damage. Thus, this study has concluded that isoquercitrin exhibits hypoglycemic and renal protective effects by inhibiting the SGLT2 pathway, indicating its potential as a promising anti-DN drug deserving further clinical investigation.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151142"},"PeriodicalIF":2.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of synthetic polymer hydrogel-based generation of leukemia stem cells.
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-12-06 DOI: 10.1016/j.bbrc.2024.151149
Saori Sawai, Yoshitaka Oda, Yusuke Saito, Takeru Kuwabara, Lei Wang, Zen-Ichi Tanei, Shinsuke Hirabayashi, Masumi Tsuda, Jian Ping Gong, Atsushi Manabe, Shinya Tanaka
{"title":"Analysis of synthetic polymer hydrogel-based generation of leukemia stem cells.","authors":"Saori Sawai, Yoshitaka Oda, Yusuke Saito, Takeru Kuwabara, Lei Wang, Zen-Ichi Tanei, Shinsuke Hirabayashi, Masumi Tsuda, Jian Ping Gong, Atsushi Manabe, Shinya Tanaka","doi":"10.1016/j.bbrc.2024.151149","DOIUrl":"https://doi.org/10.1016/j.bbrc.2024.151149","url":null,"abstract":"<p><p>Leukemia stem cells (LSCs), capable of simultaneous self-renewal and differentiation, are resistant to chemotherapy and the cause of relapse in refractory cases of leukemia. As a method to rapidly generate LSCs has not been established, research on LSCs as therapeutic targets has been hampered. Here, we demonstrate that K562 leukemia cells acquired LSC properties with increase in stemness markers such as CD34, Oct3/4, and Nanog and metabolic alterations towards OXPHOS by culturing cells on synthetic polymer hydrogels. In this hydrogel-generated LSCs, single-cell RNA sequencing identified the increase in expression levels of AKR1B1 and TSPYL5, which play an essential role for stemness generation. Decrease in expression of CD34, Oct3/4, and Nanog were observed in K562 cells with knockdown of AKR1B1 and TSPYL5. These results indicate that cell culturing on synthetic polymer hydrogels can be a useful system to generate LSCs and AKR1B1 and TSPYL5 may become therapeutic targets for LSCs.</p>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"744 ","pages":"151149"},"PeriodicalIF":2.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
StCPP3 interacts with type III secretion protein HrpB7 and negatively regulates plant resistance against Ralstonia solanacearum
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-11-30 DOI: 10.1016/j.bbrc.2024.151105
Yiqian Chen , Lixiang Cheng , Xiaoying Guan, Yi Liang, Yanjiao Xue, Wenyan Zhao, Ziyue Zhang, Xiaoyan Chang, Liqin Liang, Gang Gao
{"title":"StCPP3 interacts with type III secretion protein HrpB7 and negatively regulates plant resistance against Ralstonia solanacearum","authors":"Yiqian Chen ,&nbsp;Lixiang Cheng ,&nbsp;Xiaoying Guan,&nbsp;Yi Liang,&nbsp;Yanjiao Xue,&nbsp;Wenyan Zhao,&nbsp;Ziyue Zhang,&nbsp;Xiaoyan Chang,&nbsp;Liqin Liang,&nbsp;Gang Gao","doi":"10.1016/j.bbrc.2024.151105","DOIUrl":"10.1016/j.bbrc.2024.151105","url":null,"abstract":"<div><div>Cysteine-rich polycomb-like proteins (CPP) are crucial in regulating plant stress responses while the underlying functions of CPP involving plant- <em>Ralstonia solanacaearum</em> interaction remain unknown. Here, we showed the expression patterns of a potato <em>CPP</em> gene (<em>StCPP3)</em> under phytohormone treatments, biotic and abiotic stressed and its role in resistance against of <em>R</em>. <em>solanacaearum</em> infection by loss- and gain-of-function approaches. <em>StCPP3</em> expression were up-regulated with methyl jasmonate (MeJA) and abscisic acid (ABA) while down-regulated under salicylic acid (SA), brassinosteroids (BR), high salt or low temperature treatment. Silencing the homolog gene (<em>NbCPP3</em>) in <em>Nicotiana benthamiana</em> enhanced resistance to <em>R</em>. <em>solanacaearum</em>. Over-expressing <em>StCPP3</em> in Arabidopsis increased susceptibility and decreased activity of some defense-related enzymes, suggesting its role in suppressing hypersensitive cell death and reducing <em>PR1</em> gene expression. In addition, we found that <em>StCPP3</em> could interact with Type III secretion protein HrpB7 from <em>R. solanacaearum</em>. These results provide new insight into the mechanism of <em>CPP</em>'s involvement in plant-pathogen interactions.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"Article 151105"},"PeriodicalIF":2.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing Regulatory T cell function by mevalonate pathway inhibition prevents liver fibrosis
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-11-29 DOI: 10.1016/j.bbrc.2024.151094
An-Na Bae , Hajin Lee , Huiseong Yang , Sulagna Mukherjee , Seung-Soon Im , Jae-Ho Lee , Jong Ho Park
{"title":"Enhancing Regulatory T cell function by mevalonate pathway inhibition prevents liver fibrosis","authors":"An-Na Bae ,&nbsp;Hajin Lee ,&nbsp;Huiseong Yang ,&nbsp;Sulagna Mukherjee ,&nbsp;Seung-Soon Im ,&nbsp;Jae-Ho Lee ,&nbsp;Jong Ho Park","doi":"10.1016/j.bbrc.2024.151094","DOIUrl":"10.1016/j.bbrc.2024.151094","url":null,"abstract":"<div><div>Liver fibrosis is a well-established risk factor for liver cancer development. Despite extensive mechanistic studies on liver fibrosis, the role of the immune cell network in fibrotic disease remains poorly understood. In this study, we demonstrate that regulatory T cells (Tregs) are involved in preventing liver fibrosis by regulating the mevalonate pathway. Blocking the mevalonate pathway increased the granzyme B secretion from Tregs, while restoring the pathway reduced it. Statin treatment, which inhibits the mevalonate pathway, alleviated liver fibrosis progression and enhanced the immunosuppressive function of Tregs <em>in vivo</em>. Mechanistically, mevalonate products, including geranylgeranyl pyrophosphate, inhibited the phosphorylation and activation of LKB1, that is a key regulator of Treg homeostasis. Furthermore, these products disrupted the interaction between LKB1 and cAMP-dependent protein kinase (PKA), leading to further reduction of LKB1 phosphorylation. These findings suggest that targeting LKB1 in Tregs through statin treatment prevents the progression of liver fibrosis, offering a promising and safe therapeutic strategy for liver disease and liver cancer.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"742 ","pages":"Article 151094"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptional and post-transcriptional regulation of whiB6 by a response regulator PhoP and a small noncoding RNA MTS1338 in Mycobacterium tuberculosis
IF 2.5 3区 生物学
Biochemical and biophysical research communications Pub Date : 2024-11-29 DOI: 10.1016/j.bbrc.2024.151093
Krishan Kumar, Tanmay Dutta
{"title":"Transcriptional and post-transcriptional regulation of whiB6 by a response regulator PhoP and a small noncoding RNA MTS1338 in Mycobacterium tuberculosis","authors":"Krishan Kumar,&nbsp;Tanmay Dutta","doi":"10.1016/j.bbrc.2024.151093","DOIUrl":"10.1016/j.bbrc.2024.151093","url":null,"abstract":"<div><div>WhiB6 in pathogenic mycobacteria is highly upregulated during NO stress, hypoxia, and macrophage infection. Its expression primarily results from transcriptional control by a two-component response regulator PhoP in response to the various stresses exerted on mycobacterial cells inside phagosomes. Herein, we investigated the transcriptional and posttranscriptional regulatory mechanism of <em>whiB6</em> expression. We found that PhoP binds to the PhoP-signature sequences located upstream to the core promoter region of <em>whiB6</em> gene and controls its expression at the transcriptional level. Phosphorylation of PhoP is obligatory for binding to <em>whiB6</em> promoter. A dormancy regulatory factor DosR, although doesn't bind to <em>whiB6</em> gene, can bind to the PhoP-bound <em>whiB6</em> gene implicating its potential role in <em>whiB6</em> expression. A virulence-associated sRNA MTS1338 directly binds to the coding region of <em>whiB6</em> gene presumably protecting it from cellular ribonucleases. Induction of MTS1338 in response to low pH and oxidative stress increases <em>whiB6</em> accumulation likely through the stabilization of <em>whiB6</em> transcript at the posttranscriptional level. This study substantially increases our knowledge of the regulation of <em>whiB6</em> expression in <em>M. tuberculosis</em>.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"741 ","pages":"Article 151093"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142744272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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