MOLECULES
·
2019
·Vol. 24
·期 3
·387
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IF 3.06
Zhiliang Yu,Yuyi Zhu,Jianv Fu,Juanping Qiu,Jianhua Yin
The commonly believed mechanism of colistin against Gram-negative bacteria is to cause cell membrane lysis, whereas the mechanism of colistin against Gram-positive bacteria is extremely fragmented. In this study, we found that colistin treatment onBacillus subtilisWB800,Paenibacillus polymyxaC12 andPaenibacillus polymyxaATCC842 enhances not only the activities of α-ketoglutaric dehydrogenase and malate dehydrogenase in tricarboxylic acid (TCA) cycle, but also the relative expression levels of their encoding genes. Additionally, the oxaloacetate concentration also increases. Interestingly, the analysis of the relative expression of genes specific for respiratory chain showed that colistin treatment stimulates the respiratory chain in Gram-positive bacteria. Accordingly, the NAD+/NADH ratio increases and the oxidative level is then boosted up. As a result, the intensive oxidative damages are induced in Gram-positive bacteria and cells are killed. Notably, both rotenone and oligomycin, respectively, inhibiting NADH dehydrogenase and phosphorylation on respiratory chain can downgrade oxidative stress formation, thus alleviating the colistin-induced killing of Gram-positive cells. Besides, thiourea-based scavenging for reactive oxygen species also rescues the colistin-subjected cells. These data collectively demonstrate that colistin stimulates both TCA cycle and respiratory chain in Gram-positive bacteria, leading to the enhancement of NADH metabolism and resulting in the generation of oxidative damages in Gram-positive cells. Our studies provide a better understanding of antibacterial mechanism of colistin against Gram-positive bacteria, which is important for knowledge on bacterial resistance to colistin happening via the inhibition of respiratory chain and manipulation of its production.Keywords:colistin;Gram-positive bacteria;oxidative stress;TCA cycle;respiratory chain
研究领域:
微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2025
·
IF 5.1
Zhongmiao Wang,Jie Hou,Jiang Xu,Kun Yang,Daohui Lin
Microorganisms are pivotal in decomposing persistent organic pollutants in the environment. However, the bioavailability of pollutants is often hindered by their strong adsorption to ubiquitous fine colloids. This study provides the first evidence that Rhodococcus biphenylivorans, a known intracellular oxidative degradation bacterium, can reductively degrade organochlorine pollutants adsorbed on biochar colloids (BCCs) extracellularly, besides the oxidative degradation of BCC-adsorbed pollutants intracellularly. Over a 30 day biodegradation period, the total biodegradation rates of adsorbed 2,4,4′-trichlorobiphenyl (PCB28, 10 mg L−1) on BCCs (1 g L−1) prepared at pyrolysis temperatures of 300, 500, and 700 °C were 59.4%, 34.8%, and 10.4%, respectively. The biodegradation products of adsorbed PCB28 on low-temperature BCCs were mainly chlorosubstituted-2-hydroxy-6-oxo-6-phenyl-2,4-hexadienoic acid-type products, while in the high-temperature BCC system, dichlorobiphenyl was the main product. Mechanistically, BCCs with low pyrolysis temperature could fragment during the degradation, facilitating the transport of adsorbed PCB28 into bacteria for the intracellular oxidative degradation; the interactions between bacterial cells and BCCs (especially with high pyrolysis temperature) could stimulate the respiratory chain electron efflux for the extracellular dechlorination degradation. These findings not only provide new insights into the modulatory influence of BCCs on microbial degradation of pollutants, but also enrich our knowledge on the environmental fate of colloid-adsorbed pollutants.
研究领域:
环境科学
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微生物学
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产品关联
DOI
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2020
·
IF 3.383
Fan Zhao,Luchen Sun,Nanfei Yang,Wei Zheng,Pingping Shen,Yahong Huang,Yan Lu
Extensive literature has demonstrated that acute myeloid leukaemia (AML) cells show enhanced mitochondrial biogenesis and increased reliance on oxidative phosphorylation (OXPHOS) compared with normal hematopoietic progenitors, and one hallmark of AML leukaemia blasts is myeloid differentiation blockade. However, relatively few reports have linked these processes. Recent studies have indicated that therapies that overcome differentiation arrest represent an effective treatment strategy. Here, we identified that the disruption of the mitochondrial mass and energy metabolism promotes leukaemia cellular myeloid differentiation. In this study, we showed that acute monocytic leukaemia (AML-M5) cells package mitochondria in microvesicles (MVs) when MVs shed from membranes. Additionally, during myeloid differentiation, we report for the first time that differentiated leukaemia cells release more MVs than undifferentiated leukaemia cells. Targeting the formation of MVs using a specific inhibitor (Y-27632) restrained myeloid differentiation, suggesting that the increased release level of MVs plays an important role in regulating myeloid differentiation. Furthermore, the intracellular mitochondria and ATP levels were decreased after leukaemia cells overcame the differentiation blockade. Moreover, rotenone , which is used to inhibit the respiratory chain and ATP production, had a strong effect on myeloid differentiation in monocytic leukaemia cells. Collectively, these studies uncovered the relationship between mitochondrial function and myeloid differentiation and may provide more insight into the diagnosis and treatment of AML.
研究领域:
血液学
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肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
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2022
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IF 4.755
Li Sheng,Wang Zhi,Yao Jing Wen,Jiao Hong Chao,Wang Xiao Juan,Lin Hai,Zhao Jing Peng
To uncover the molecular mechanism underlying glucocorticoid-induced loss of mitochondrial integrity in skeletal muscles, studies were performed to investigate whether the peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-mediated pathway was involved in this process. In an in vivo trial, 3 groups of 30-d-old Arbor Acres male broilers were randomly subjected to one of the following treatments for 7 days: corticosterone (CORT, 30 mg/kg diet), control (blank), and pair-feeding (restricted to the same feed intake as for the CORT treatment), each with 6 replicates of 15 birds. Mitochondrial abundance, morphology, and function were determined in the pectoralis major and biceps femoris muscles. In an in vitro trial, a primary culture of embryonic chick myotubes was incubated with a serum-free medium for 24 h in the presence or absence of CORT (0, 200, and 1,000 nM). Results showed that CORT destroyed mitochondrial ultrastructure (p < 0.01), and decreased the enzymatic activity and protein expression of respiratory chain complexes (p < 0.05), leading to an inferior coupling efficiency (p < 0.05). As reflected by a decline in mitochondrial density (p < 0.01) and mitochondrial DNA copy number (p < 0.05), CORT reduced mitochondrial contents. Among all three PGC-1 family members, only PGC-1β was down-regulated by CORT at the protein level (p < 0.05). Some aspects of these responses were tissue-specific and seemed to result from the depressed feed intake. Overall, CORT may impair mitochondrial biogenesis and oxidative phosphorylation in a PGC-1β-dependent manner in chicken muscles.
研究领域:
动物科学
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分子生物学
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内分泌学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2022
·
IF 6.212
Zizhen Zhao,Chen Fu,Yuping Zhang,Yingying Zhang,Xiaoxi Yang,Ailing Fu
The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo . The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
DOI
高影响因子
Journal of Integrative Neuroscience
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2025
·Vol. 24
·期 8
·40079
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IF 2.7
Jixin Chen,Guoyou Chen,Yueheng Wu,Shuai Liu,Yifan Ma,Maonan Liu,Wei Yu
Background and Purpose:Ciprofol, a novel intravenous anesthetic, has been shown to exert protective effects against ischemic stroke, a leading cause of death and disability; however, its molecular mechanisms remain unclear. This study aimed to explore the molecular mechanisms underlying the neuroprotective effects of ciprofol using metabolomics.Methods:This study used a middle cerebral artery occlusion (MCAO) rat model to simulate cerebral ischemia-reperfusion injury (CIRI). The rats were divided into ciprofol, MCAO, and sham groups. Histological and neurobehavioral testing methods were used to investigate the therapeutic effects of ciprofol in rats. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to screen for differential metabolites and related metabolic pathways in the serum and brain of the three groups. Spectrophotometry was used to detect in vitro mitochondrial respiratory chain complex I (MRCC-I) activity.Results:Neurological behavioral scores and cerebral infarct volumes of rats in the ciprofol group were significantly lower than those of rats in the MCAO group. Metabolomic analysis revealed 19 differential metabolites in serum samples and 31 differential metabolites in brain samples, including flavin mononucleotide (FMN). These metabolites were mainly enriched in the tricarboxylic acid cycle, respiratory electron transport chain, and amino acid and lipid metabolism. In vitro experiments demonstrated that ciprofol promoted the activity of MRCC-I during CIRI by increasing FMN levels.Conclusion:The mechanisms of action of ciprofol during treatment of cerebral ischemia involve the tricarboxylic acid cycle, respiratory electron transport chain, and amino acid and lipid metabolism and may directly affect MRCC-I activity by regulating FMN.
研究领域:
麻醉药理学
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神经生物学
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代谢组学
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线粒体功能
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脑血管病
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分子药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2023
·
IF 5
Deng Hong,Du Zhengda,Lu Surui,Wang Zhaoyue,He Xiuping
Abstract Cat8 is a C6 zinc cluster transcription activator in yeast. It is generally recognized that the transcription of CAT8 is inhibited and that Cat8 is inactive in the presence of high concentrations of glucose. However, our recent study found that constitutively overexpressed Cat8 played a regulatory role in Saccharomyces cerevisiae in the presence of 20 g/L glucose . To explore the regulatory network of Cat8 at high glucose concentrations, CAT8 was both overexpressed and deleted in this study. Cell growth and glucose consumption in different media were significantly accelerated by the deletion of CAT8 , while the lag period was greatly shortened. RNA-seq and genetic modification showed that the deletion of CAT8 changed the type of energy metabolism in yeast cells. Many genes related to the mitochondrial respiratory chain were downregulated, resulting in a reduction in aerobic respiration and the tricarboxylic acid cycle. Meanwhile, both the energy supply of anaerobic ethanol fermentation and the Crabtree effect of S. cerevisiae were enhanced by the deletion of CAT8 . CAT8 knockout cells show a higher sugar uptake rate, a higher cell growth rate, and higher tolerance to glucose than the wild-type strain YS58. This study expands the understanding of the regulatory network of Cat8 and provides guidance for modulating yeast cell growth. Key points • The deletion of CAT8 promoted cell growth of S. cerevisiae. • Transcriptome analysis revealed the regulation network of Cat8 under 1% glucose condition. • CAT8 deletion increases the glucose tolerance of cells by enhancing the Crabtree effect.
研究领域:
分子生物学
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微生物学
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遗传学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2018
·Vol. 8
·期 1
·1-11
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IF 4.122
Li Huihui,Zhao Hongting,Hao Shuangying,Shang Longcheng,Wu Jing,Song Chuanhui,Meyron-Holtz Esther G.,Qiao Tong,Li Kuanyu
Iron is essential for growth and proliferation of mammalian cells. The maintenance of cellular iron homeostasis is regulated by iron regulatory proteins (IRPs) through binding to the cognate iron-responsive elements in target mRNAs and thereby regulating the expression of target genes. Irp1 or Irp2 -null mutation is known to reduce the cellular iron level by decreasing transferrin receptor 1 and increasing ferritin. Here, we report that Irp1 or Irp2 -null mutation also causes downregulation of frataxin and IscU, two of the core components in the iron-sulfur cluster biogenesis machinery. Interestingly, while the activities of some of iron-sulfur cluster-containing enzymes including mitochondrial aconitase and cytosolic xanthine oxidase were not affected by the mutations, the activities of respiratory chain complexes were drastically diminished resulting in mitochondrial dysfunction. Overexpression of human ISCU and frataxin in Irp1 or Irp2 -null cells was able to rescue the defects in iron-sulfur cluster biogenesis and mitochondrial quality. Our results strongly suggest that iron regulatory proteins regulate the part of iron sulfur cluster biogenesis tailored specifically for mitochondrial electron transport chain complexes.
研究领域:
分子生物学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
GeroScience
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2024
·
IF 5.3
Cao Haiming,Xie Qigen,Luo Peng,Chen Jiaqi,Xia Kai,Ma Lin,Chen Demeng,Deng Chunhua,Wan Zi
Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6 months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300 μM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72 h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5 mM NAC for 1 h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.
研究领域:
毒理学
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内分泌学
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生殖生物学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2021
·
IF 4.527
Hao Ma,Sue Yang,Meng li,Xiaoning Tang,Zhenhao Xia,Rong Dai
Effective and safe application of antibacterials has always been an important aspect for their usage. High-efficiency photocatalytic technology driven by visible light for antibacterial action constitutes a practical solution for antibacterial agents and will not harm the human body or the environment. While most studies on β-Bi 2 O 3 materials with good photocatalytic properties under visible light are conducted in the field of optoelectronics , their potential and mechanism as photocatalytic antibacterial agents have not yet been fully explored. Herein, we report the performance of sheet-like metastable β-Bi 2 O 3 material with rich oxygen vacancies and high electron-hole separation efficiency in antibacterial processes, as well as a preliminary exploration of its antibacterial mechanism. The results revealed that the antibacterial activity of the product against E. coli greatly improved in comparison with commercially available α-Bi 2 O 3 owing to its excellent structure and optical properties . In addition, gradient experiments and scavenger experiments have confirmed that the main antibacterial effect of β-Bi 2 O 3 originates from reactive oxygen species (ROS), and the superoxide radical, ·O 2 − , of generated ROS is the key reactive species in the antibacterial process. Through the detection of lipid peroxidation and bacterial respiratory-chain dehydrogenase activity, several pathways were identified for the excellent antibacterial activity of the product.
研究领域:
材料科学
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纳米技术
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光催化
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抗菌技术
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
Computational and Structural Biotechnology Journal
·
2024
·
IF 4.4
Jian Wang,Meina Zhang,Chao Li,Mengyuan Liu,Yixin Qi,Xiaolin Xie,Changlin Zhou,Lingman Ma
Antimicrobial peptides are promising therapeutic agents for treating drug-resistant bacterial disease due to their broad-spectrum antimicrobial activity and decreased susceptibility to evolutionary resistance. In this study, three novel cathelicidin antimicrobial peptides were identified from Thamnophis sirtalis , Balaenoptera musculus , and Lipotes vexillifer by protein database mining and sequence alignment and were subsequently named TS-CATH, BM-CATH, and LV-CATH, respectively. All three peptides exhibited satisfactory antibacterial activity and broad antibacterial spectra against clinically isolated E. coli , P. aeruginosa , K. pneumoniae , and A. baumannii in vitro . Among them, TS-CATH displayed the best antimicrobial/bactericidal activity, with a rapid elimination efficiency against the tested drug-resistant gram-negative bacteria within 20 minutes, and exhibited the lowest cytotoxicity toward mammalian cells. Furthermore, TS-CATH effectively enhanced the survival rate of mice with ceftazidime-resistant E. coli bacteremia and promoted wound healing in meropenem-resistant P. aeruginosa infection. These results were achieved through the eradication of bacterial growth in target organs and wounds, further inhibiting the systemic dissemination of bacteria and the inflammatory response. TS-CATH exhibited direct antimicrobial activity by damaging the inner and outer membranes, resulting in leakage of the bacterial contents at super-MICs. Moreover, TS-CATH disrupted the bacterial respiratory chain, which inhibited ATP synthesis and induced ROS formation, significantly contributing to its antibacterial efficacy at sub-MICs. Overall, TS-CATH has potential for use as an antibacterial agent.
研究领域:
微生物学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2019
·
IF 5.714
Bingnan He,Xia Wang,Jianbo Zhu,Baida Kong,Lai Wei,Yuanxiang Jin,Zhengwei Fu
The immunotoxicity of synthetic pyrethroid (SPs) has garnered much attention, and our previous research demonstrated that β-CYP causes immunotoxicity and oxidative stress in macrophages. Nevertheless, the underlying mechanism remains largely unknown. In this study, the murine macrophage RAW 264.7 cells and murine peritoneal macrophages (PMs) were exposed to β-CYP. The results showed that β-CYP elevated intracellular ROS levels in both RAW 264.7 cells and PMs. Exposure to β-CYP also caused mitochondrial dysfunction with reduced mitochondrial membrane potential (MMP), intracellular ATP level and mitochondrial DNA (mtDNA) content in the two cell types. In addition, exposure of RAW 264.7 cells to β-CYP for 12 h and 24 h enhanced autophagy, with elevated Beclin1, Rab7, Lamp1 and LC3-II expression levels, while 48 h of exposure attenuated autophagy. In contrast, exposure of PMs to β-CYP for 12 h promoted autophagy, whereas exposure for 24 h and 48 h impaired autophagy. Cotreatment with an antioxidant, N-acetyl-L-cysteine (NAC), partially blocked the reduced MMP, intracellular ATP level and autophagy disturbance. Moreover, cotreatment with an autophagy agonist, rapamycin (RAPA), partially blocked mitochondrial dysfunction and oxidative stress in the two cell types, whereas cotreatment with an autophagy inhibitor, 3-methyladenine (3-MA), augmented the abovementioned toxic effects. Furthermore, mitochondrial ROS levels in both RAW 264.7 cells and PMs were elevated by exposure to β-CYP, and molecular docking showed that β-CYP docked with mouse respiratory chain complex I by binding to the ND2, ND4, and ND5 subunits of the protein complex. Taken together, the data obtained in the present study demonstrate that oxidative stress partially mediates mitochondrial dysfunction and autophagy disturbance upon exposure to β-CYP in macrophages, and autophagy plays a protective role against the toxic effects.
研究领域:
免疫毒理学
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细胞生物学
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毒理学
✓ 已验证
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）