FUNGAL GENETICS AND BIOLOGY
·
2019
·
IF 3.314
Yinshan Zhang,Limin Wang,Shen Liang,Panpan Zhang,Ruijiao Kang,Mengjuan Zhang,Min Wang,Linlin Chen,Hongxia Yuan,Shengli Ding,Honglian Li
Histone deacetylases (HDACs) play essential roles in modulating chromatin structure to provide accessibility to gene regulators. Increasing evidence has linked HADCs to pathogenesis control in the filamentous plant fungi. However, its function remains unclear in Fusarium pseudograminearum, which has led to the emergence of the disease Fusarium crown rot in China. Here we identified the FpDEP1 gene, an orthologue of Saccharomyces cerevisiae DEP1 encoding a component of the Rpd3 histone deacetylase complex in F. pseudograminearum . The gene deletion mutant, ΔFpdep1, showed significantly retarded growth on PDA plates with reduced aerial hyphae formation. Pathogenicity tests displayed no typical leaf lesions and limited expansion capability of coleoptiles. Histopathological analysis indicated the ΔFpdep1 deletion mutant differentiated infectious hyphae and triggered massive reactive oxygen species (ROS) accumulation during the early infection stage, resulting in limited expansion to neighbor cells which was concurring with sensitivity to H 2 O 2 and SDS tests in vitro. FM4-64 staining revealed that the ΔFpdep1 deletion mutant was delayed in endocytosis. The FpDEP1-GFP transgene complemented the mutant phenotypes and the fusion protein co-localized with DAPI staining, indicating that the FpDEP1 gene product is localized to the nucleus in spores and mycelia. Immunoprecipitation coupled with LC-MS/MS and yeast two-hybrid screening identified the Rpd3L-like HDAC complex containing at least FpDep1, FpSds3, FpSin3, FpRpd3, FpRxt3, FpCti6, FpRho23, and FpUme6. These results suggest that FpDep1 is involved in a HDAC complex functioning on fungal development and pathogenesis in F. pseudograminearum .
研究领域:
真菌学
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分子生物学
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植物病理学
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DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2021
·Vol. 87
·期 8
·
IF 4.792
Chao-Fan Yin,Ying Xu,Shi-Kai Deng,Wen-Long Yue,Ning-Yi Zhou
As a water-soluble polymer, the widely used polyvinyl alcohol (PVA) is produced from hydrolysis of polyvinyl acetate. Microbial PVA carbon backbone cleavage via a two-step reaction of dehydrogenation and hydrolysis has been well studied. The content of the acetyl group is a pivotal factor affecting performance of PVA derivatives in industrial applications, and deacetylation is a nonnegligible part of PVA degradation. However, the genetics and biochemistry of its deacetylation remain largely elusive. Here, Comamonas sp. strain NyZ500 was isolated for its capability of growing on acetylated PVA from activated sludge. The spontaneous PVA utilization-deficient mutant strain NyZ501 was obtained when strain NyZ500 was cultured in rich media. Comparative analysis between the genomes of these two strains revealed a fragment (containing a putative hydrolase gene, dacApva) deletion in strain NyZ501, and in the dacApva-complemented strain NyZ501 the ability to grow on PVA was restored. DacApva, which shares 21% identity with xylan esterase AxeA1 from Prevotella ruminicola 23, is a unique deacetylase catalyzing the conversion of acetylated PVA and its derivatives to deacetylated counterparts. This indicates that strain NyZ500 utilizes acetylated PVA via acetate as a carbon source to grow. DacApva also possesses the ability to deacetylate acetylated xylan and the antibiotic intermediate 7-aminocephalosporanic acid (7ACA), but the enzymes responsible for the conversion of those two compounds have no activity against PVA derivatives. This study enhanced our understanding of the diversity of microbial degradation of PVA, and DacApva characterized here is also a potential biocatalyst for the eco-friendly biotransformation of PVA derivatives and other acetylated compounds.IMPORTANCE Water-soluble PVA, which possesses a very robust ability to accumulate in the environment, has a very grave environmental impact due to its widespread use in industrial and household applications. On the other hand, chemical transformation of PVA derivatives is currently being carried out under high-energy-consumption and high-pollution conditions using hazardous chemicals (such as NaOH and methanol) under high temperatures. The DacApva reported here performs PVA deacetylation under mild conditions, so it has great potential to be developed into an eco-friendly biocatalyst for biotransformation of PVA derivatives. DacApva also has deacetylation activity for compounds other than PVA derivatives, which facilitates its development into a broad-spectrum deacetylation biocatalyst for production of certain desired compounds.
研究领域:
环境科学
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生物化学
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微生物学
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DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 39
·
IF 12.5
Yuyu Guo,Cunliang Li,Yao Liu,Hanyi Mao,Yin Zhang,Pascal Genschik,Lili Wang,Shunping Yan
Plants have evolved sophisticated mechanisms to balance growth and defense. The evolutionarily conserved polymerase-associated factor 1 complex (PAF1C) plays multiple roles in transcription. Here, we show that PAF1C regulates the growth-defense tradeoff by repressing defense genes expression in Arabidopsis . Loss of PAF1C leads to increased expression of defense genes, enhanced disease resistance, but compromised growth. Mechanistically, PAF1C binds to defense genes, where it interacts with histone deacetylases, such as HDA6, to promote histone deacetylation, thereby repressing defense genes expression. The plant immune hormone salicylic acid (SA) promotes the interaction between PAF1 and the SA receptor NPR1, which functions as an E3 ubiquitin ligase to mediate the polyubiquitination and degradation of PAF1. Genetically, loss of PAF1 suppresses the immune defects of the npr1 mutant, supporting the notion that PAF1 functions downstream of NPR1. Collectively, this study identifies the NPR1-PAF1C-HDA6 module that regulates the growth-defense tradeoff.
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DOI
PubMed
高影响因子
Frontiers in Physiology
·
2025
·
IF 3.4
Ziqin Wei,Hongfang Mu,Fangfang Qiu,Minghui Zhao,Xiaojing Zhang,Wenbin Li,Hai Jia,Rong Wang
Objective Previous research has demonstrated that the hypoxic environment at high altitudes significantly alters the pharmacokinetics of many drugs, reducing their efficacy and increasing adverse effects. A key factor in this altered drug metabolism is the inhibition of ATP-binding cassette subfamily B member 1 (ABCB1), an efflux transporter protein, in the liver tissues of plateau rats. Rat ABCB1, encoded by the ABCB1A and ABCB1B genes, has two isoforms functionally analogous to human ABCB1. Histone acetylation, an epigenetic mechanism, may regulate ABCB1 transcription in hypoxic conditions by modifying chromatin structure and interacting with signaling pathways. However, its role in ABCB1 transcriptional regulation under hypoxia remains unclear. Based on this, the present study employed the BRL cell line to establish a hypoxia model, aiming to investigate the histone acetylation-mediated regulatory mechanisms of ABCB1 expression under hypoxic conditions, with the ultimate goal of providing novel theoretical foundations for rational drug use in high-altitude regions. Methods Establishment of BRL hypoxia model: BRL cell viability was detected by CCK-8 assay, and HIF-1α expression was measured by RT-qPCR and Western blot. After treating the BRL hypoxia model with HDAC inhibitors, ABCB1 and HDAC5 expression were detected by RT-qPCR, Western blot, and immunofluorescence. Rhodamine 123 accumulation assay was performed to examine the effect of HDAC inhibitors on ABCB1 functional activity. HDAC5 was targeted by siRNA technology to detect ABCB1 and H3K9ac expression. CUT&Tag assay was used to measure H3K9ac levels at the ABCB1 promoter region. After SAHA treatment of the BRL hypoxia model, SP1 expression was detected by RT-qPCR and Western blot. Combined treatment with SAHA and siRNA targeting SP1 was performed to detect ABCB1 expression. Co-immunoprecipitation and fluorescence colocalization assays were conducted to examine interactions among SP1, HDAC5, and ABCB1. Results After hypoxic culture for different durations, cell viability decreased while HIF-1α expression increased, indicating the successful establishment of the BRL hypoxia model. In the BRL hypoxia model, ABCB1 and SP1 expression decreased while HDAC5 expression increased. After SAHA treatment, ABCB1 and SP1 expression were upregulated while HDAC5 was downregulated. Rhodamine 123 accumulation assay showed that SAHA could enhance ABCB1 functional activity by inducing its expression. After HDAC5 was knocked down using siRNA, ABCB1 and H3K9ac expression increased, and ABCB1 functional activity was enhanced. CUT&Tag assay demonstrated that H3K9ac levels at the ABCB1B promoter region decreased in the BRL hypoxia model, while HDAC5 inhibition increased H3K9ac levels at this region. After SP1 was knocked down using siRNA, the inductive effect of SAHA on ABCB1 was blocked. Co-immunoprecipitation and fluorescence colocalization showed interactions among SP1, HDAC5, and ABCB1. Conclusion In BRL cells, HDAC5 may be recruited by SP1 to form a complex, reducing free HDAC5, increasing H3K9ac at the ABCB1B promoter, and activating ABCB1 transcription. In the BRL hypoxia model, disruption of the SP1-HDAC5 complex increased free HDAC5, lowered H3K9ac at the ABCB1B promoter, and suppressed ABCB1 transcription. These results suggest that HDAC inhibitors enhance ABCB1 expression in hypoxic environments, indicating that combining HDAC inhibitors with therapeutic agents could mitigate reduced drug efficacy and adverse effects caused by ABCB1 suppression.
研究领域:
药理学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-26
·
IF 6
Wei Xuehua,Xiong Xiangpeng,Wang Pingping,Zhang Shufang,Peng Dongxian
Background The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance.Methods High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues.Results High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein–protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC.Conclusion This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2025
·Vol. 22
·期 1
·1-19
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IF 10.1
Chi Zhexi,Lu Bo,Liu Rongjun,Pan Chen,Meng Bo,Xing Xiuzhong,Yuan Hui,Wu Xuewei,Chen Yushan,Ren Yuxuan,Wu Wenwei,Miao Mengmeng,Chen Junping,Chen Xiaowei
Neuropathic pain, a debilitating nerve injury-induced condition, remains a significant clinical challenge. This study evaluates the effect of histone deacetylase 6 (HDAC6) inhibition in a spared nerve injury (SNI) mouse model. Systemic administration of the selective HDAC6 inhibitor ACY-1215 (20 mg/kg/day, 14 days), alleviated SNI-induced pain in mice of both sexes. ACY-1215 increased acetylated signal transducer and activator of transcription 3 (Ac-STAT3) and reduced phosphorylated STAT3 (p-STAT3) in the lumbar spinal cord of SNI mice. HDAC6 and p-STAT3 were expressed in spinal dorsal horn neurons, and SNI-enhanced HDAC6/STAT3 interaction was reversed by ACY-1215. Neuronal STAT3 overexpression induced pain hypersensitivity and elevated p-STAT3, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), effects suppressed by ACY-1215. Cytokine profiling identified CC-chemokine ligand 7 (CCL7) as a key downstream effector of the HDAC6/STAT3 axis, with ACY-1215 attenuating SNI-induced CCL7 upregulation. HDAC6 knockdown in neurons reduced p-STAT3, while HDAC6 or STAT3 knockdown diminished CCL7 production. These findings demonstrate that ACY-1215 mitigates neuropathic pain by modulating STAT3 acetylation/phosphorylation and suppressing HDAC6/STAT3-driven CCL7 and cytokine release. This study underscores the role of the HDAC6/STAT3/CCL7 signaling axis in neuropathic pain and highlights the therapeutic potential of HDAC6 inhibitors for pain management.
研究领域:
神经科学
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药理学
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DOI
PubMed
高影响因子
npj Precision Oncology
·
2025
·Vol. 9
·期 1
·1-13
·
IF 8
Wang Zexuan,Guo Yaoyu,Hu Kefei,He Tingjiang,Qin Tong,Zhang Ludan,Xu Fang,Xu Yuanzhi,Cheng Mingjiao,Zhang Jintao,Zhao Qianwei
Phosphoglycerate mutase 2 (PGAM2) is a crucial glycolytic enzyme. Recently, we have found that both the protein and acetylation levels of PGAM2 are down-regulated in hepatocellular carcinoma (HCC) tissues. However, the functional significance of PGAM2 in HCC progression remains poorly characterized. In this study, we demonstrated that PGAM2 functioned as a tumor suppressor in HCC progression, and knockdown of PGAM2 promoted proliferation of HCC cells and tumor growth both in vitro and in vivo. Moreover, we identified lysine 100 (K100) in PGAM2 as the predominant deacetylation site of sirtuin-2 (SIRT2), and that deacetylation of K100 destabilized PGAM2 by promoting its ubiquitination and degradation. Importantly, we discovered that PGAM2 suppressed aerobic glycolysis through an enzymatic activity-independent mechanism in HCC cells. Mechanistic investigations revealed that PGAM2 knockdown upregulated lactate dehydrogenase A (LDHA) expression via activation of the signal transducer and activator of transcription 3 (STAT3). Furthermore, we found that knockdown of PGAM2 sensitized HCC cells to sorafenib treatment. In conclusion, these findings elucidate the tumor-suppressive role of PGAM2 in HCC progression and its post-translational regulation through SIRT2-mediated deacetylation, which provide novel biomarkers and therapeutic targets for HCC treatment.
研究领域:
肿瘤学
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分子生物学
·
代谢研究
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Donghao Gan,Yi Ran,Hong Pan,Qinnan Yan,Wenjing Zhang,Bo Zhou,Pengzhi Xu,Rongdong Liao,Haipeng Xue,Will Jiang,Tailin He,Qingyun Jia,Lei Qin,Francis Y Lee,Di Chen,Chuanju Liu,Guozhi Xiao
The mechanosensitive Piezo1 channel protein plays a pivotal role in promoting bone formation and repair; however, its underlying molecular mechanism(s) are poorly defined. Here this study shows that Sirt1 positively regulates Piezo1 expression and activity to promote osteogenesis and bone repair in mice. This study finds that Piezo1 is up-regulated in the cartilage callus during bone repair. Deleting Piezo1 in chondrocytes largely impairs endochondral ossification and mechanically induced osteogenesis and delays fracture healing in mice, while Yoda1 activation of Piezo1 exerts opposite effects. Sirt1 overexpression or activation dramatically increases Piezo1 protein expression in a dose-dependent manner. Sirt1 binds to Piezo1 protein and deacetylates and activates Piezo1 and Ca 2+ influx in chondrocytes. Piezo1 loss in chondrocytes abolishes the ability of Sirt1 activator SRT2104 to accelerate bone repair. Resveratrol (RSV), a natural Sirt1 activator, also potently activates Piezo1 and enhances bone repair. A yeast microcapsule-based oral formulation of RSV (YC-RSV) is developed to improve drug bioavailability and therapeutic efficacy, which highly and selectively targets to the inflammatory fracture site. Thus, it demonstrates that Sirt1 is a novel and potent activator of Piezo1 to promote bone formation and repair, supporting the potential clinical application of Sirt1 activators in promoting bone formation and repair.
研究领域:
分子生物学
·
骨骼生物学
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再生医学
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信号转导
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 3
·717
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IF 3.267
Na Zhao,Feifei Yang,Lina Han,Yuhua Qu,Di Ge,Hua Zhang
Histone deacetylases (HDACs) have been proved to be promising targets for the treatment of cancer, and five histone deacetylase inhibitors (HDACis) have been approved on the market for the treatment of different lymphomas. In our previous work, we designed a series of novel coumarin-containing hydroxamate HDACis, among which compounds6and7displayed promising activities against tumor growth. Based on a molecular docking study, we further developed 26 additional analogues with the aim to improve activity of designed compounds. Several of these new derivatives not only showed excellent HDAC1 inhibitory effects, but also displayed significant growth inhibitory activities against four human cancer cell lines. Representative compounds,13aand13c, showed potent anti-proliferative activities against solid tumor cell lines with IC50values of 0.36–2.91 µM and low cytotoxicity against Beas-2B and L-02 normal cells. Immunoblot analysis revealed that13aand13cdose-dependently increased the acetylation of histone H3 and H4. Importantly, the two compounds displayed much better anti-metastatic effects than SAHA against the MDA-MB-231 cell line. Moreover,13aand13carrested MDA-MB-231 cells at G2/M phase and induced MDA-MB-231 cell apoptosis. Finally, the molecular docking study rationalized the high potency of compound13c.Keywords:coumarin;anti-tumor;HDAC inhibitors;structural modification;anti-proliferative
研究领域:
肿瘤学
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药物化学
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癌症研究
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
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IF 9.8
Ting Zhuo,Jun-ru Qi,Jin-song Liao,Hui-ying Wei,Rong Xiao
Konjac glucomannan (KGM) is a natural functional polysaccharide, and deacetylation (removing acetyl groups) impacts its physicochemical and gel properties. In order to study KGM's gel properties and explore new deacetylation modifiers, three deacetylated konjac glucomannan (DKGM) with different deacetylation degrees (DD, 17.51 %, 35.41 %, and 54.52 %) were prepared using L-arginine. Results showed that L-arginine deacetylated and retained the main structure and high molecular weight of KGM. Solubility decreased from 85.38 % to 81.17 %, transparency decreased from 38.52 % to 35.73 %, water absorbing and swelling slowed down, and molecular morphology changed from chain structures to micelle-like aggregates after deacetylation. Dynamic viscoelastic analysis showed that deacetylation facilitated the formation of the entangled network structure of KGM. The strength of konjac glucomannan and κ-carrageenan mixed gels increased after deacetylation, and this enhancement was mainly through hydrogen bonds and hydrophobic interactions. These findings will provide theoretical guidance for the application of KGM.
研究领域:
食品科学
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高分子化学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
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IF 3.7
Zhenyin Huang,Hanyu Dong,Yingjie Qiu,Aiping Chang,Hu Zhu
Sphingan WL gum (WL) is an extracellular polysaccharide with a carboxyl group produced by Sphingomonas sp. WG. Recently, we have successfully obtained deacetylated WL (DWL) with good water solubility by alkaline treatment. In this study, a DWL-based microgel (named DWLM) with semi-interpenetrating network structure was constructed for the first time and used to deliver the oral drug ciprofloxacin hydrochloride (CIP). DLS results suggested that DWLM had a dual response to pH and temperature. The in vitro cumulative drug release curves showed that the amount of CIP released from the microgel was higher at pH 6.8 than that at pH 3.0. Biocompatibility assessments using HEK293T showed that cell viability was 75.9 ± 1.7% at the DWLM-CIP concentration of 4 mg/mL. While, the cell viability of CIP at the same concentration was only 54.9 ± 1.0%, indicating that DWLM-CIP has good biocompatibility. Antimicrobial performance tests revealed that DWLM-CIP at a concentration of 1 mg/mL could effectively inhibit the growth of Escherichia coli for up to 4 days. When the concentration of DWLM-CIP reached 4 mg/mL, the growth of Staphylococcus aureus was effectively suppressed for up to 3 days, demonstrating the long-lasting antimicrobial efficacy of DWLM-CIP. All of these results indicate that DWL-based microgels have great potential as oral drug delivery carriers.
研究领域:
生物材料学
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药剂学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
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IF 3.909
Yan Hu,Jing Tian,Jian Zou,Xiaoqing Yuan,Jing Li,Hongshan Liang,Fuchao Zhan,Bin Li
The main aim of the current study was to research the effect of the degree of konjac deacetylation on the rheological and textural properties of konjac glucomannan (KGM) and κ-carrageenan blends. A series of deacetylated konjac glucomannan (Da-KGM) with different degrees of deacetylation (0, 20.35%, 35.62%, 57.19%, and 74.01%) was prepared by a heterogeneous deacetylation method. The rheological and textural properties of mixed sols and gels of Da-KGM with different degrees of deacetylation and κ-carrageenan were determined. The results showed that the viscosities of mixed sols of Da-KGM and κ-carrageenan decreased with increasing degree of deacetylation. The partial removal of acetyl groups from konjac glucomannan could significantly improve the hardness and springiness of mixed gels of KGM and κ-carrageenan. Meanwhile, decreasing the acetyl content could decrease the syneresis of mixed gels. By regulating the deacetylation degree of konjac, gels with high gel strength could be prepared, which provides a new idea for the production of high-strength gelatin food.
研究领域:
食品科学
·
高分子化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）