MOLECULES
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2017
·Vol. 22
·期 5
·798
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IF 2.861
Jia Wang,Guangzhi Zeng,Xiaobing Huang,Zhe Wang,Ninghua Tan
Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, we screened 790 phytochemicals using the model organismCaenorhabditis elegansand found 10 active compounds, 3 of which were further evaluated for their inhibitory activities against egg hatching ofC. elegansand J2Meloidogyne incognita.Among them, 1,4-naphthoquinone (1,4-NQ) was the only compound that could kill more than 50% of targets at 50 μg/mL, prompting us to investigate how 1,4-NQ triggers nematode lethality. InC. elegans, we observed that 1,4-NQ could influence reactive oxygen production, superoxide dismutase activity, and the heat-shock transcription factor (HSF)-1 pathway, which indicated that 1,4-NQ stimulated significant oxidative stress. Furthermore, using quantitative RT-PCR and transgenetic nematodes, we revealed that 1,4-NQ lethality was related to the Insulin/IGF signaling (IIS) pathway, and the effect of 1,4-NQ on IIS pathway related genes indicated that 1,4-NQ could activate this pathway and suppress the expression of DAF-16 target genes. The triggering of oxidative stress and activation of the IIS pathway indicated that 1,4-NQ operates through the generation of oxygen radicals, which can be lethal toC. elegans, thus making it an interesting lead compound for the development of future nematocides.Keywords:plant-parasitic nematode;phytochemical;nematocidal;1,4-naphthoquinone;oxidative stress;insulin/IGF signaling pathway;Caenorhabditis elegans
研究领域:
植物科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 10
·4471-4483
·
IF 5.396
Siqi Jiang,Na Deng,Bisheng Zheng,Tong Li,Rui Hai Liu
The effects of Rhodiola extract (RE) on longevity and stress resistance in Caenorhabditis elegans (C. elegans), and the underlying molecular mechanisms were explored in the present study. Results showed that the lifespan of C. elegans was remarkably prolonged by 37.1% after treated with high-dose RE (480 μg mL−1). Intervention with RE alleviated aging-related declines in the C. elegans model, and enhanced the stress resistance against heat shock, ultraviolet radiation and paraquat. Moreover, RE reduced the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and catalase (CAT). RE also upregulated the gene expression of sod-3, gst-4, daf-16, skn-1 in C. elegans, downregulated the gene expression of daf-2 and age-1, and accelerated the translocation of DAF-16 and SKN-1 into the nucleus. Furthermore, the daf-16(mu86) and skn-1(zu169) mutants reversed the extension of lifespan triggered by RE, indicating that these genes were involved in RE-regulated longevity. These results demonstrated that RE could enhance lifespan extension, healthspan and stress resistance of C. elegans via insulin/IGF signaling and SKN-1 pathways. Therefore, the present findings suggested Rhodiola as a potential candidate to ameliorate the symptoms of aging.
研究领域:
老年学
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分子生物学
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药理学
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PubMed
高影响因子
Cell Discovery
·
2023
·Vol. 9
·期 1
·1-18
·
IF 33.5
Gao Xiu Kui,Sheng Zu Kang,Lu Ye Hong,Sun Yu Ting,Rao Xi Sheng,Shi Lin Jing,Cong Xiao Xia,Chen Xiao,Wu Hao Bo,Huang Man,Zheng Qiang,Guo Jian-sheng,Jiang Liang Jun,Zheng Li Ling,Zhou Yi Ting
The scaffold protein IRS-1 is an essential node in insulin/IGF signaling. It has long been recognized that the stability of IRS-1 is dependent on its endomembrane targeting. However, how IRS-1 targets the intracellular membrane, and what type of intracellular membrane is actually targeted, remains poorly understood. Here, we found that the phase separation-mediated IRS-1 puncta attached to endoplasmic reticulum (ER). VAPB, an ER-anchored protein that mediates tethers between ER and membranes of other organelles, was identified as a direct interacting partner of IRS-1. VAPB mainly binds active IRS-1 because IGF-1 enhanced the VAPB-IRS-1 association and replacing of the nine tyrosine residues of YXXM motifs disrupted the VAPB-IRS-1 association. We further delineated that the Y745 and Y746 residues in the FFAT-like motif of IRS-1 mediated the association with VAPB. Notably, VAPB targeted IRS-1 to the ER and subsequently maintained its stability. Consistently, ablation of VAPB in mice led to downregulation of IRS-1, suppression of insulin signaling, and glucose intolerance. The amyotrophic lateral sclerosis (ALS)-derived VAPB P56S mutant also impaired IRS-1 stability by interfering with the ER-tethering of IRS-1. Our findings thus revealed a previously unappreciated condensate-membrane contact (CMC), by which VAPB stabilizes the membraneless IRS-1 signalosome through targeting it to ER membrane.
研究领域:
细胞生物学
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分子生物学
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内分泌学
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神经退行性疾病
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PubMed
高影响因子
Comparative Biochemistry and Physiology D-Genomics & Proteomics
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2023
·
IF 3
Cheng Zhao,Sijin Wang,Yuxi Liu,Peng Chu,Bing Han,Xianhui Ning,Tao Wang,Shaowu Yin
Temperature is a critical factor that regulates the reproduction processes in teleost. However, the gonadal response mechanism to cold stress in fish remains largely unknown. In the present study, female zebrafish were exposed to different extents of low temperatures at 18 °C and 10 °C for 48 h. The ovarian histology was remarkably damaged after cold stress exposure. Integrated analysis of miRNA-mRNA was used to investigate the ovarian response to acute cold stress. A large number of mRNAs and miRNAs were altered by cold stress, which are involved in extensive biological processes . It is indicated that the signal transduction of MAPK and Calcium signaling pathway is highly engaged in zebrafish ovary to adapt to cold stress. The immune system was dysregulated by cold stress while the ovarian autophagy was activated. Remarkably increased gene number related to reproductive functions was identified in the cold stress at 10 °C compared to the control. The cold stress-induced dysregulated reproductive genes include star , hsd3b1 , hsd17b1 , inha , insl3 , amh , nanos1 and foxl2 . Combined with the dysregulated insulin, IGF and progesterone signaling, it is suggested that cold stress affects ovarian function in multiple aspects, including oocyte meiosis, folliculogenesis , final maturation and ovarian maintenance. On the other hand, the ovarian miRNA-mRNA regulatory network response to cold stress was also constructed. Overall, our result revealed the ovarian response to cold stress in zebrafish and provided insight into the fish adaptation mechanism to acute temperature change.
研究领域:
水生生物学
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生殖生物学
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分子生物学
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基因组学
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PubMed
高影响因子
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