Disease relevance of Idh1

• Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity [1].
• We demonstrate significant reduction of both Id-1 and MT1-MMP expressions as well as the metastatic spread of 4T1 breast cancer cells in syngeneic BALB/c mice [2].
• Further, to more accurately recapitulate the biology of and potential therapeutic approaches to tumor metastasis, we targeted Id-1 expression systemically in tumor-bearing mice by using a nonviral approach [2].
• In addition, Id-1 is aberrantly over-expressed in aggressive and metastatic breast cancer cells, as well as in human breast tumor biopsies from infiltrating carcinomas, suggesting Id-1 might be an important regulator of breast cancer progression [2].
• Transplantation of beta2-microglobulin(-/-) nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34(+) cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development [3].

High impact information on Idh1

• Down-regulation of Id1 by RNA interference impaired C/EBPalpha-induced granulocytic differentiation [4].
• Mammary epithelial cells constitutively expressing Id-1 protein are unable to differentiate, acquire the ability to proliferate, and invade the extracellular matrix [2].
• In conclusion, our studies have identified Id-1 as a critical regulator of breast cancer progression and suggest the feasibility of developing novel therapeutic approaches to target Id-1 expression to reduce breast cancer metastasis in humans [2].
• Here we show that Id1-null primary mouse embryo fibroblasts undergo premature senescence despite normal growth profiles at early passage [5].
• Although much recent data has implicated Id1 in playing a critical role in modulating cellular senescence, no direct genetic evidence has been reported to substantiate such work [5].

Chemical compound and disease context of Idh1

• In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice [6].

Biological context of Idh1

• We have used a mouse cDNA clone for the S-antigen to map the corresponding gene, Sag, to mouse chromosome 1 near Idh-1 [7].
• Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc [8].
• However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells [8].
• Cells with decreased expression of IDPc or IDPm had elevated reactive oxygen species generation, lipid peroxidation and protein oxidation [9].
• Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1 [10].

Anatomical context of Idh1

• During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner [1].
• Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced [3].
• A novel enhancer, the pro-B enhancer, regulates Id1 gene expression in progenitor B cells [11].
• We sought to map transcriptional Smad1/5 activity in development by generating embryonic stem cell lines carrying a Smad1/5-specific response element derived from the Id1 promoter coupled to beta-galactosidase or luciferase as reporters [12].
• RESULTS: In immunoblot analyses, using whole mammary gland extracts, Id-1 was detected [13].

Associations of Idh1 with chemical compounds

• The genetic loci determining the activity of these isozymes (designated Aox-1 and Aox-2, respecitively) are closely linked on chromosome 1 near Id-1 (encoding the soluble isozyme of isocitrate dehydrogenase) [14].
• We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis [1].
• Suppression of collagen-1 production did not depend on MAPK or guanylate cyclase signaling pathways but did depend on the transcriptional regulator Id1 [15].
• This finding indicates that IDPc is essential for the efficient glutathione recycling [8].
• Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione [8].

Other interactions of Idh1

• The backcross offsprings were analyzed with respect to Elo, Idh-1, Cryg-1, and Cryg-4 loci [16].
• Close linkage of the dominant cataract mutations (Cat-2) with Idh-1 and cryge on mouse chromosome 1 [17].
• Linkage between the Lsh locus and the Chromosome 1 marker Id-1 was detected using several sets of recombinant inbred strains [18].
• To generate appropriate strains of mice for the study of these genes, a series of 10 C.D2 congenic strains recombinant across a 28-centimorgan interval of mouse chromosome 1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3 congenic strain back to BALB/cAn [19].
• Sas-2 was located by linkage analysis between Idh-1 locus and Akp-1 locus on chromosome 1 [20].

Analytical, diagnostic and therapeutic context of Idh1

• MATERIALS AND METHODS: Changes of IDPc and IDPm proteins upon gamma-ray irradiation to NIH3T3 cells were analysed by immunoblotting [9].
• Using stable transfectants, transient transfection, and mobility shift assays, we have identified an 8-bp element designated PBE (pro-B enhancer) downstream of the Id1 gene that is responsible for a pro-B-cell-specific enhancer activity [11].
• Molecular cloning and characterization of a zinc finger protein involved in Id-1-stimulated mammary epithelial cell growth [21].
• Therefore, to assess the precise significance of Id-1 in mammary biology and carcinogenesis, we examined its cellular localization in vivo using immunohistochemistry [13].
• DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group [6].

References