MID-1
目录号 : GC61516
MID-1 is a disruptor of MG53-IRS-1 (Mitsugumin 53-insulin receptor substrate-1) interaction, which can disrupts molecular association of MG53 with IRS-1 and abolishes MG53-induced IRS-1 ubiquitination and degradation in skeletal muscle, leading to elevated IRS-1 expression level and increased insulin signaling and glucose uptake.
Cas No.:312608-54-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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MID-1 is a disruptor of MG53-IRS-1 (Mitsugumin 53-insulin receptor substrate-1) interaction, which can disrupts molecular association of MG53 with IRS-1 and abolishes MG53-induced IRS-1 ubiquitination and degradation in skeletal muscle, leading to elevated IRS-1 expression level and increased insulin signaling and glucose uptake.
[1] Lee H, et al. J Biol Chem. 2016 Dec 23;291(52):26627-26635.
| Cas No. | 312608-54-1 | SDF | |
| Canonical SMILES | O=C(NC1=NC=C([N+]([O-])=O)S1)C2=CC=C(OCC)C=C2 | ||
| 分子式 | C12H11N3O4S | 分子量 | 293.3 |
| 溶解度 | DMSO: 31.25 mg/mL (106.55 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4095 mL | 17.0474 mL | 34.0948 mL |
| 5 mM | 0.6819 mL | 3.4095 mL | 6.819 mL |
| 10 mM | 0.3409 mL | 1.7047 mL | 3.4095 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Calcineurin responsive zinc-finger-1 binds to a unique promoter sequence to upregulate neuronal calcium sensor-1, whose interaction with MID-1 increases tolerance to calcium stress in Neurospora crassa
Mol Microbiol 2019 Jun;111(6):1510-1528.PMID:30825330DOI:10.1111/mmi.14234.
We studied the molecular mechanism of neuronal calcium sensor-1 (NCS-1) signaling pathway for tolerance to Ca2+ stress in Neurospora crassa. Increasing concentration of Ca2+ increased the expression of ncs-1; however, the calcineurin inhibitor FK506 severely reduced ncs-1 mRNA transcript levels. Chromatin immunoprecipitation (ChIP) studies revealed that the transcription factor calcineurin responsive zinc finger-1 (CRZ-1) binds to the ncs-1 promoter, and CRZ-1 binding upregulated ncs-1 expression under high Ca2+ concentrations. These results suggested the regulation of NCS-1 function through calcineurin- CRZ-1 signaling pathway. Furthermore, the electrophoretic mobility shift assay (EMSA) revealed that the CRZ-1 binds specifically to an 8 bp sequence 5'-CCTTCACA-3' in the ncs-1 promoter 216 bp upstream of the ATG start codon. We also showed that NCS-1 binds to the Ca2+ permeable channel MID-1 for tolerance to Ca2+ stress. Therefore, CRZ-1 binds to a unique sequence in the ncs-1 promoter, causing upregulation of NCS-1 that binds to MID-1 for tolerance to Ca2+ stress.
Phenotype of a mechanosensitive channel mutant, MID-1, in a filamentous fungus, Neurospora crassa
Eukaryot Cell 2008 Apr;7(4):647-55.PMID:18296620DOI:10.1128/EC.00411-07.
In the yeast Saccharomyces cerevisiae, the MID1 (mating-induced death) gene encodes a stretch-activated channel which is required for successful mating; the mutant phenotype is rescued by elevated extracellular calcium. Homologs of the MID1 gene are found in fungi that are morphologically complex compared to yeast, both Basidiomycetes and Ascomycetes. We explored the phenotype of a MID-1 knockout mutant in the filamentous ascomycete Neurospora crassa. The mutant exhibits lower growth vigor than the wild type (which is not rescued by replete calcium) and mates successfully. Thus, the role of the MID-1 protein differs from that of the homologous gene product in yeast. Hyphal cytology, growth on diverse carbon sources, turgor regulation, and circadian rhythms of the MID-1 mutant are all similar to those of the wild type. However, basal turgor is lower than wild type, as is the activity of the plasma membrane H(+)-ATPase (measured by cyanide [CN(-)]-induced depolarization of the energy-dependent component of the membrane potential). In addition, the mutant is unable to grow at low extracellular Ca(2+) levels or when cytoplasmic Ca(2+) is elevated with the Ca(2+) ionophore A23187. We conclude that the MID-1 protein plays a role in regulation of ion transport via Ca(2+) homeostasis and signaling. In the absence of normal ion transport activity, the mutant exhibits poorer growth.
A Way Forward Beyond Karl Popper's and Donald T. Campbell's Dead-End Evolutionary Epistemologies
Am J Psychol 2016;129(4):461-477.PMID:29558053DOI:10.5406/amerjpsyc.129.4.0461.
Theories of natural thought processes have traditionally served as foundations for philosophies of science. The source of all knowledge is passively received observations; these are combined to produce certain knowledge. After David Hume showed that this was not possible, deductivist alternatives, that is, theories that find a source of knowledge in ideas not derived from observations, from Immanuel Kant to William Whewell in the MID-1 9th century, were introduced. In response, traditional associationist and inductivist views were refurbished; a deductivist alternative was developed by the W6rzburg School. Much later Karl Popper in philosophy and Donald T. Campbell in psychology integrated this view with evolutionary theory. Campbell wanted thereby to find a justificationist view, which would reduce philosophy of science to cognitive psychology; Popper rejected both justificationism and the reduction of philosophy of science to psychology. Campbell thought all rational processes were innate psychological processes; Popper thought psychological processes were used to develop various rational processes. Campbell could not show that all rational thought was reducible to innate psychological processes, nor how some justification of scientific theories was possible. Popper could not show how evolutionary theory contributed to our knowledge of psychological thought processes. Both failed to observe that cognitive processes are social; people have learned how to think by learning how to interact in social groups seeking understanding. When innate thought processes are studied as social characteristics, evolutionary theory can contribute to both cognitive psychology and the theory of rationality, as both Popper and Campbell wanted it to do.
Phosphorylation and microtubule association of the Opitz syndrome protein MID-1 is regulated by protein phosphatase 2A via binding to the regulatory subunit alpha 4
Proc Natl Acad Sci U S A 2001 Jun 5;98(12):6650-5.PMID:11371618DOI:10.1073/pnas.111154698.
Opitz syndrome (OS) is a human genetic disease characterized by deformities such as cleft palate that are attributable to defects in embryonic development at the midline. Gene mapping has identified OS mutations within a protein called Mid1. Wild-type Mid1 predominantly colocalizes with microtubules, in contrast to mutant versions of Mid1 that appear clustered in the cytosol. Using yeast two-hybrid screening, we found that the alpha4-subunit of protein phosphatases 2A/4/6 binds Mid1. Epitope-tagged alpha4 coimmunoprecipitated endogenous or coexpressed Mid1 from COS7 cells, and this required only the conserved C-terminal region of alpha4. Localization of Mid1 and alpha4 was influenced by one another in transiently transfected cells. Mid1 could recruit alpha4 onto microtubules, and high levels of alpha4 could displace Mid1 into the cytosol. Metabolic (32)P labeling of cells showed that Mid1 is a phosphoprotein, and coexpression of full-length alpha4 decreased Mid1 phosphorylation, indicative of a functional interaction. Association of green fluorescent protein-Mid1 with microtubules in living cells was perturbed by inhibitors of MAP kinase activation. The conclusion is that Mid1 association with microtubules, which seems important for normal midline development, is regulated by dynamic phosphorylation involving MAP kinase and protein phosphatase that is targeted specifically to Mid1 by alpha4. Human birth defects may result from environmental or genetic disruption of this regulatory cycle.
In vivo targeting of miR-223 in experimental eosinophilic oesophagitis
Clin Transl Immunology 2020 Nov 23;9(11):e1210.PMID:33282292DOI:10.1002/cti2.1210.
Objectives: Eosinophilic oesophagitis (EoE) is characterised by oesophageal inflammation, fibrosis and dysfunction. Micro (mi)-RNAs interfere with pro-inflammatory and pro-fibrotic transcriptional programs, and miR-223 was upregulated in oesophageal mucosal biopsy specimens from EoE patients. The therapeutic potential of modulating miR-223 expression in vivo has not been determined. We aimed to elucidate the relevance of oesophageal miR-223 expression in an in vivo model of EoE by inhibiting miR-223 tissue expression. Methods: The expression of miR-223 and the validated miR-223 target insulin-like growth factor receptor 1 (IGF1R) protein was determined in our paediatric cohort of EoE patients. A murine model of Aspergillus fumigatus-induced EoE was employed, and oesophagi were assessed for miR-233, IGF1R, T lymphocyte type 2 (T2) cytokine expression and eosinophil infiltration. Mice were treated with antagomirs targeting miR-223 or resveratrol targeting its upstream regulator Midline-1(MID-1). Results: There was an inverse relationship between an increased expression of miR-223 and a decreased IGF1R protein concentration in biopsy specimens from EoE patients. TNF-related apoptosis-inducing ligand deficiency, MID-1 inhibition and resveratrol treatment suppressed miR-223 expression. Furthermore, inhibition of miR-223 and treatment with resveratrol in the oesophagus resulted in an amelioration of EoE hallmark features including eosinophilic infiltration, oesophageal circumference and a reduction in T2 cytokine expression. Conclusion: miR-223 has a key role in the perpetuation of EoE hallmark features downstream of TNF-related apoptosis-inducing ligand and MID-1 in an experimental model. These studies highlight a potentially critical role of miRNA function in EoE aetiology. miR-223 expression in the oesophagus may be therapeutically modulated by resveratrol, providing a potential new therapeutic option to be explored in EoE patients for this increasingly prevalent condition.