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BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY · 2024 · IF 3.2

Enzymatic properties of ornithine decarboxylase from Clostridium aceticum DSM1496

Qian Tan,Linbo Gou,Tai-Ping Fan,Yujie Cai

Clostridium aceticum DSM1496 is an acid-resistant strain in which ornithine decarboxylase (ODC) plays a crucial role in acid resistance. In this study, we expressed ODC derived from C. aceticum DSM1496 in Escherichia coli BL21 (DE3) and thoroughly examined its enzymatic properties. The enzyme has a molecular weight of 55.27 kDa and uses pyridoxal-5′-phosphate (PLP) as a coenzyme with a K m = 0.31 mM. ODC exhibits optimal activity at pH 7.5, and it maintains high stability even at pH 4.5. The peak reaction temperature for ODC is 30°C. Besides, it can be influenced by certain metal ions such as Mn 2+ . Although l -ornithine serves as the preferred substrate for ODC, the enzyme also decarboxylates l -arginine and l -lysine simultaneously. The results indicate that ODC derived from C. aceticum DSM1496 exhibits the ability to produce putrescine, cadaverine, and agmatine through decarboxylation. These polyamines have the potential to neutralize acid in an acidic environment, facilitating the growth of microorganisms. These significant findings provide a strong basis for further investigation into the acid-resistant mechanisms contributed by ODC.

研究领域: 微生物学 · 生物化学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2025 ·Vol. 29 ·期 6 ·e70372 · IF 4.2

Elucidation of Dexmedetomidine-Induced Analgesic Tolerance Mechanisms in Neuropathic Pain With Modulation of SGK1, NR2A, and NR2B Expression via the Spinal SGK1/NF-κB Signalling Pathway

Wang Huikang,Cao Shiya,Pan Di,Faisal Ayub Kiani,Li Hao,Nan Sha,Lin Xuan,Mahmoud M. Abouelfetouh,Zulfiqar Ahmed,Ding Mingxing,Ding Yi

Neuropathic pain (NP), resulting from nerve damage, is difficult to manage and often requires long-term treatment. However, prolonged use of pain medications can lead to addiction and reduced effectiveness over time. Understanding drug tolerance is essential for developing improved pain management strategies. Dexmedetomidine (DEX) is effective in targeting the α2 -adrenergic receptor, providing relief from pain, especially NP. However, its extended use leads to tolerance and hinders its clinical utility. Herein, we investigated tolerance mechanisms and potential applications of this drug in managing NP. Adult C57BL/6 mice (male) were distributed into DEX Dosage Groups ( n = 48), DEX Tolerance Model Groups ( n = 32), SGK1 Inhibitor GSK650394 Groups ( n = 48), and NF - κB Inhibitor PDTC Groups ( n = 32) to explore dexmedetomidine's effects on NP and tolerance mechanisms. NP was established via selective ligation of the sciatic nerve branch (SNI), followed by administration of DEX. The results revealed a dose-dependent analgesic effect of DEX, with significant increases in pain thresholds observed compared to the sham group ( p < 0.05). Optimal efficacy was found at a dose of 30 μg/kg, indicating its potential as an effective treatment for NP ( p < 0.05). However, continuous administration of DEX over 13 days induced analgesic tolerance, evidenced by an initial increase in pain thresholds followed by a gradual decrease ( p < 0.05). Despite an initial efficacy in elevating pain thresholds, the analgesic effect of DEX diminished over time, returning to pre-dose levels after 5 days ( p < 0.05). Transcriptome sequencing of spinal cord samples from mice receiving multiple DEX injections revealed differential gene expression patterns, notably upregulation of SGK1 , NR2A , and NR2B subunits ( p < 0.05). Inhibiting SGK1 mitigated DEX-induced tolerance, suggesting its involvement in tolerance development ( p < 0.05). Moreover, NF - κB inhibition reversed DEX-induced tolerance and implicated the SGK1 - NF - κB pathway in the mediation of analgesic tolerance. To sum up, these findings revealed the molecular mechanism underlying DEX-induced analgesic tolerance in the NP model and offer potential avenues for future therapeutic interventions.

CAS / MDL: 113775-47-6
研究领域: 药理学 · 疼痛管理 · 分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2020 · IF 4.872

Metabolomics reveals the “Invisible” detoxification mechanisms of Amaranthus hypochondriacus at three ages upon exposure to different levels of cadmium

Xie Mengdi,Dai Haibo,Liu Jiaxin,Xue Zhe,Chen Yi,Liang Xuan,Mou Haiyan,Sun Hui,Ao Tianqi,Li Yunzhen,Chen Wenqing

To decipher the Cd hyperaccumulation and tolerance mechanisms of plants and increase phytoremediation efficiency, in this study, the physiological effects induced by environmentally relevant concentrations (0, 25 and 200 mg/kg) of Cd were characterized in Amaranthus hypochondriacus (K472) at three growth stages using LC/MS-based metabolomics. Metabolomic analysis identified 31, 29 and 30 significantly differential metabolites (SDMs) in K472 exposed to Cd at the early, intermediate and late stages of vegetative growth, respectively. These SDMs are involved in nine metabolic pathways responsible for antioxidation, osmotic balance regulation, energy supplementation and the promotion of metabolites that participate in phytochelatin (PC) synthesis. K472 at the intermediate stage of vegetative growth had the strongest tolerance to Cd with the combined action of Ala, Asp and Glu metabolism, purine metabolism, Gly, Ser and Thr metabolism and Pro and Arg metabolism. Among these crucial metabolic biomarkers, purine metabolism could be the primary regulatory target for increasing the Cd absorption of K472 for the restoration of Cd-contaminated soil.

CAS / MDL: 7697-37-2
研究领域: 植物学 · 环境科学 · 代谢组学
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MicrobiologyOpen · 2017 ·Vol. 6 ·期 4 ·e00485 · IF 2.747

A proteomic-based investigation of potential copper-responsive biomarkers: Proteins, conceptual networks, and metabolic pathways featuring Penicillium janthinellum from a heavy metal-polluted ecological niche

Xin Feng,Jian Xu,Yu Liang,Guo-Li Chen,Xian-Wei Fan,You-Zhi Li

Graphical Our work not only provides the potential protein biomarkers indicating the Cu pollution, target metabolic steps for engineering the Cu-tolerant fungi during bioremediation, but also presents clues for insight into heavy metal tolerance mechanisms of other eukaryotes. Filamentous fungi-copper (Cu) interactions are very important in the formation of natural ecosystems and the bioremediation of heavy metal pollution. However, important issues at the proteome level remain unclear. We compared six proteomes from Cu-resistant wild-type (WT) Penicillium janthinellum strain GXCR and a Cu-sensitive mutant (EC-6) under 0, 0.5, and 3 mmol/L Cu treatments using iTRAQ. A total of 495 known proteins were identified, and the following conclusions were drawn from the results: Cu tolerance depends on ATP generation and supply, which is relevant to glycolysis pathway activity; oxidative phosphorylation, the TCA cycle, gluconeogenesis, fatty acid synthesis, and metabolism are also affected by Cu; high Cu sensitivity is primarily due to an ATP energy deficit; among ATP generation pathways, Cu-sensitive and Cu-insensitive metabolic steps exist; gluconeogenesis pathway is crucial to the survival of fungi in Cu-containing and sugar-scarce environments; fungi change their proteomes via two routes (from ATP, ATP-dependent RNA helicases (ADRHs), and ribosome biogenesis to proteasomes and from ATP, ADRHs to spliceosomes and/or stress-adapted RNA degradosomes) to cope with changes in Cu concentrations; and unique routes exist through which fungi respond to high environmental Cu. Further, a general diagram of Cu-responsive paths and a model theory of high Cu are proposed at the proteome level. Our work not only provides the potential protein biomarkers that indicate Cu pollution and targets metabolic steps for engineering Cu-tolerant fungi during bioremediation but also presents clues for further insight into the heavy metal tolerance mechanisms of other eukaryotes.

CAS / MDL: 7440-50-8 13721-39-6
研究领域: 环境生物学 · 蛋白质组学 · 微生物学
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2023 · IF 6

Potential mechanism of improved cryotolerance of Pediococcus pentosaceus YT2 by cold acclimation based on TMT quantitative proteomics analysis

Zheng Zhang,Qiyao Xu,Mengxing Gou,Chang Zhu,Wanchun Guo,Ruifeng Hu,Liyan Wang,Xuejun Liu

Lactic acid bacteria (LAB) are used in fermented foods to overcome the shortcomings of traditional fermentation methods, such as long cycles and poor safety. However, the application of LAB in low-temperature foods is limited by their growth temperature. This study aimed to quantitatively compare the proteins of the YT2 strain acclimated at 37, 28, 20, 15, 8, and 4 °C (YT-4) and that grown at 37 °C (YT-37) using tandem mass tag (TMT) proteomics and bioinformatics analysis to elucidate the potential mechanism of cryotolerance of P. pentosaceus YT2. Altogether, 1416 quantitative proteins were identified, of which 747 were differentially abundant between the YT-4 and YT-37 strains. Functional enrichment analysis showed that the upregulated proteins were mainly involved in nucleotide transport, metabolism, translation, ribosomal structure and biogenesis, transcription, replication, recombination, and repair, while the downregulated proteins were involved in lipid, amino, and carbohydrate transport and metabolism. These results were validated for eight upregulated and five downregulated proteins using parallel reaction monitoring (PRM). Our study analyzed the potential mechanism underlying the improved cryotolerance of P. pentosaceus YT2 at 4 °C, which may enable the utilization of LAB in low-temperature applications.

CAS / MDL: 144-48-9
研究领域: 微生物学 · 食品科学 · 蛋白质组学
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BIORESOURCE TECHNOLOGY · 2021 · IF 9.642

Enhanced removal efficiency of sulfamethoxazole by acclimated microalgae: Tolerant mechanism, and transformation products and pathways

Yibo Zhang,Jing Wan,Zhang Li,Zhenbing Wu,Chenyuan Dang,Jie Fu

This study utilized sulfamethoxazole (SMX) acclimatization to enhance the tolerance and biodegradation capacity of Chlorella vulgaris . Compared to wild C. vulgaris , the growth inhibition and oxidative damage induced by SMX evidently decreased in acclimated C. vulgaris , and meanwhile photosynthetic and antioxidant activities were significantly promoted. The physiological analyses with the aid of principal component analysis revealed the increase of catalase and glutathione reductase activities was the critical tolerant mechanism of acclimated C. vulgaris . As the consequence, the acclimated C. vulgaris exhibited enhanced efficiency and (pseudo-first-order) kinetic rate for removal of SMX. The distribution analysis of residual SMX demonstrated the biodegradation was the major removal mechanism of SMX by C. vulgaris , while bioadsorption and bioaccumulation made pimping contributions. During the degradation process of SMX, nine transformation products (TPs) were identified. Based on the identified TPs, a possible transformation pathway was proposed.

CAS / MDL: 64-18-6
研究领域: 环境科学 · 微生物学 · 生物技术
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Environmental Science-Processes & Impacts · 2023 · IF 5.5

Toxicity and tolerance mechanism of binary zinc oxide nanoparticles and tetrabromobisphenol A regulated by humic acid in Chlorella vulgaris

Yi Liu,Mengen Kang,Yuzhu Weng,Yuanyuan Ding,Xue Bai

Recent studies have reported that nanoparticles (NPs) released into the aquatic environment may interact with persistent organic pollutants such as brominated flame retardants, whereas the environmental processes and toxicological impacts induced by such binary NPs require further specification. This study investigated the ultrastructural damage of Chlorella vulgaris triggered by exposure to zinc oxide (ZnO) NPs, tetrabromobisphenol A (TBBPA), ZnO–TBBPA, and ZnO–TBBPA–humic acid (HA), clarified the uptake and distribution of ZnO NPs in cells, and explored the physiological toxicity and tolerance mechanism. The results demonstrated that ZnO NPs induced irregular morphology in algal cells, and the disruption of the cellular ultrastructure by binary ZnO–TBBPA was also extremely severe due to the excessive uptake of ZnO NPs, which resulted in strong oxidative stress responses. In particular, the accumulation of reactive oxygen species further exacerbated the reduction of total chlorophyll content and algal density. Moreover, the cluster heat map and correlation analysis revealed that superoxide dismutase activity played a critical role in alleviating lipid peroxidation damage and enhancing the tolerance of algal cells to the stress of binary ZnO NPs. More notably, the existence of HA intensified the dispersion stability of NP suspensions and significantly mitigated the synergistic toxicity of binary ZnO–TBBPA. This study provides new insights into the environmental behavior and biological impacts of binary NPs in the natural environment.

CAS / MDL: 79-94-7 7647-01-0
研究领域: 环境科学 · 毒理学 · 植物学
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Foods · 2024 ·Vol. 13 ·期 21 ·3405 · IF 4.7

Elucidating Bile Acid Tolerance in Saccharomyces cerevisiae: Effects on Sterol Biosynthesis and Transport Protein Expression

Miao Zheng,Qi Su,Haoqing Wu,Chenggang Cai,Le Thanh Ninh,Haiying Cai

The tolerance of Saccharomyces cerevisiae to high concentrations of bile acids is intricately linked to its potential as a probiotic. While the survival of yeast under high concentrations of bile acids has been demonstrated, the specific mechanisms of tolerance remain inadequately elucidated. This study aims to elucidate the tolerance mechanisms of S. cerevisiae CEN.PK2-1C under conditions of elevated bile acid concentrations. Through growth curve analyses and scanning electron microscopy (SEM), we examined the impact of high bile acid concentrations on yeast growth and cellular morphology. Additionally, transcriptomic sequencing and molecular docking analyses were employed to explore differentially expressed genes under high bile acid conditions, with particular emphasis on ATP-binding cassette (ABC) transporters and steroid hormone biosynthesis. Our findings indicate that high concentrations of bile acids induce significant alterations in the sterol synthesis pathway and transporter protein expression in S. cerevisiae . These alterations primarily function to regulate sterol synthesis pathways to maintain cellular structure and sustain growth, while enhanced expression of transport proteins improves tolerance to elevated bile acid levels. This study elucidates the tolerance mechanisms of S. cerevisiae under high bile acid conditions and provides a theoretical foundation for optimizing fermentation processes and process control.

研究领域: 微生物学 · 分子生物学 · 生物技术
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Metabolites · 2024 ·Vol. 14 ·期 8 ·449 · IF 3.4

Tolerance Mechanisms and Removal Efficiency of Chlorella pyrenoidosa in Treating 3-Fluorophenol Pollution

Min Li,Zhenfang Shang,Yonglan Ma,Huijun Zhao,Zhijing Ni,Zhaojun Wei,Xiu Zhang

This study investigates the growth tolerance mechanisms ofChlorella pyrenoidosato 3-fluorophenol and its removal efficiency by algal cells. Our results indicate thatC. pyrenoidosacan tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed by promotion of growth. InC. pyrenoidosacells, the activities of superoxide dismutase (SOD) and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were higher than or comparable to the control group. Metabolic analysis revealed that the 3-fluorophenol treatment activated pathways, such as glycerol phospholipid metabolism, autophagy, glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, and phenylpropanoid biosynthesis, contributed to the stabilization of cell membrane structures and enhanced cell repair capacity. After 240 h of treatment, over 50% of 3-fluorophenol was removed by algal cells, primarily through adsorption. Thus,C. pyrenoidosashows potential as an effective biosorbent for the bioremediation of 3-fluorophenol.

CAS / MDL: 372-20-3
研究领域: 环境科学 · 生物技术 · 微生物学 · 生物化学
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