Disease relevance of LOC298111

• Using this technique, it was found that host liver contained alpha2U-globulin mRNA at normal levels, whereas hepatoma tissue contained no detectable mRNA coding for this protein [1].
• Comparison of in vivo translation rates and messenger RNA levels of alpha2U-globulin in rat liver and Morris hepatoma 5123D [1].
• The level of the specific mRNA coding for alpha2U-globulin can be quantitated using in vitro translation of polyadenylate-containing RNA in a Krebs II ascites cell-free translational system, followed by immunoprecipitation of the alpha2U-globulin synthesized in vitro [1].
• Sustained increases in cell proliferation in these studies depend on the presence of a chemical-alpha G complex in phagolysosomes of P2 proximal tubule cells, which results in cytotoxicity and compensatory hyperplasia only in male F344 rats, but not female F344 rats or alpha G deficient male NBR rats [2].
• Doubting nongenotoxic mechanisms of renal cancer: comparing apples and oranges in the alpha2u-globulin hypothesis [3].

High impact information on LOC298111

• Tissue-specific control of alpha 2u globulin gene expression: constitutive synthesis in the submaxillary gland [4].
• Thus the liver and submaxillary gland synthesize alpha 2u globulin from different sets of genes that are subject to very different developmental and hormonal control [4].
• Synthesis of alpha 2u globulin, previously thought to occur only in the male rat liver, has now been demonstrated in the submaxillary salivary gland [4].
• Salivary alpha 2u globulin mRNA manifests 5% nucleotide divergence, encoding 20 amino acid substitutions, which specifies a more acidic polypeptide than its hepatic counterpart [4].
• Protection of spermatogenesis by alpha2u globulin in rats treated with oestrogen [5].

Chemical compound and disease context of LOC298111

• However, a general demethylation of cytosine residues in the alpha 2u globulin genes of hepatomas has been found using the restriction enzyme Hha I and the isoschizomeric pair of restriction enzymes Msp I and Hpa II [6].
• Influence of neonatal androgenization on the response of alpha 2u-globulin to testosterone and dexamethasone in the rat [7].
• This mode of action reflects a sustained regenerative response, either due to direct chemical toxicity to the tubule cells, as with chloroform, or to indirect cytotoxicity associated with lysosomal overload, as in alpha2u-globulin accumulation in male rats resulting from the administration of such chemicals as d-limonene and tetrachloroethylene [8].
• The role of alpha2u-globulin in ochratoxin A induced renal toxicity and tumors in F344 rats [9].
• Treatment of adult male rats with estradiol-17 beta for 7 days results in adrenal hyperplasia, increased level of serum ACTH along with reduction in serum level of alpha 2u-globulin and inhibition of adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity [10].

Biological context of LOC298111

• To explore whether induction of this mRNA is a direct or an indirect consequence of the interaction of the dexamethasone-receptor complex with the alpha 2u-globulin genome, the requirement for ongoing protein synthesis was examined [11].
• Sustained androgen receptivity delays age-dependent decline in the synthesis of the androgen-inducible alpha 2u globulin and derepression of the androgen-repressible senescence marker protein (SMP-2) [12].
• In hepatoma 5123D, however, a small number of alpha 2u globulin RNA sequences were detected by Northern blot and R0t analysis, but this RNA was not detectably translationally active either in vivo or in an in vitro cell-free translational system [6].
• These results indicate that growth hormone regulates the synthesis of alpha 2u-globulin by acting at a step antecedent to mRNA translation [13].
• Delayed secondary glucocorticoid response elements. Unusual nucleotide motifs specify glucocorticoid receptor binding to transcribed regions of alpha 2u-globulin DNA [14].

Anatomical context of LOC298111

• Furthermore, incorporation of 3H-labeled amino acids into total protein was decreased by only 40-50%, and the appearance of the dexamethasone-induced glycosylated forms of alpha 2u-globulin was completely prevented in these cycloheximide-treated hepatocytes [11].
• The rat alpha 2u globulin gene family encodes approximately 20 low-molecular-weight (20,000) proteins with pIs ranging from 4.5 to 7.9. alpha 2u globulin protein isoforms were detected in the liver and in the submaxillary, lachrymal, preputial, and mammary glands of Sprague-Dawley rats [15].
• Castrated male rats have reduced levels of alpha 2u globulin in serum and liver cytosol, as measured by a radial immunodiffusion assay [16].
• Studies in the adult male hypothyroid rat, a known GH-deficient animal, have shown hepatic alpha 2U-globulin mRNA to be dependent on thyroid hormones [17].
• Multihormonal induction of alpha 2u-globulin in an established rat hepatoma cell line [18].

Associations of LOC298111 with chemical compounds

• Initial treatment of these animals with 5 alpha-dihydrotestosterone, followed by actinomycin D, resulted within 2-3 hr in a more than 2-fold increase in hepatic alpha 2u globulin compared to animals treated with the androgen alone [19].
• Superinduction of alpha 2u globulin by actinomycin D: evidence for drug-mediated increase in alpha 2u mRNA [19].
• Cycloheximide inhibition of hormonal induction of alpha 2u-globulin mRNA [11].
• The results suggest that the synthesis of a protein mediator(s) may be required for the induction of alpha 2u-globulin mRNA by glucocorticoids and that the steroid-receptor complex may not interact directly with the alpha 2u-globulin genome [11].
• In a 2-year carcinogenesis bioassay, d-limonene (dL) induced kidney tumors in male F344 rats, but not in female F344 rats or either sex of mice, d-Limonene-1,2-oxide, a metabolite of dL, has been shown to bind reversibly the male rat-specific urinary protein, alpha2u-globulin (alpha 2u-G), lysosomal degradation than alpha 2u-G alone [20].

Analytical, diagnostic and therapeutic context of LOC298111

• Spayed female rats with a marginally induced state of alpha 2u synthesis showed an approximately 5-fold increase in hepatic alpha 2u globulin within 3-6 hr after treatment with actinomycin D [19].
• The presence of alpha 2u-globulin was confirmed and quantitated by radioimmunoassay [21].
• The synthesis of the male rat hepatic protein alpha2U-globulin has been examined in Morris hepatoma 5123D and male host liver using pulse incorporation of labeled amino acids in vivo, followed by immunoprecipitation of the newly synthesized alpha2U-globulin from the soluble protein fraction of liver and hepatoma tissue [1].
• A variety of liver-derived cell culture lines also did not have alpha2U-globulin synthesis [1].
• The effect of hypophysectomy on the synthesis of alpha 2u-globulin can be reversed by multiple hormone treatment [13].

References