Disease relevance of LOC259246

• Concurrently the acute phase response depresses the hepatic synthesis of albumin and alpha 2u-globulin and their mRNA levels [1].
• The toxicity is characterized by an increase in protein droplets in proximal convoluted tubular cells and an increase in the renal concentration of the male-rat-specific protein alpha 2u-globulin [2].
• These data suggest that neonatal androgenization directly or indirectly influences the availability for transcription and/or the transcription rate of alpha 2u-globulin genes in the liver [3].

High impact information on LOC259246

• These results indicate that similar to hepatic parenchymal cells pancreatic hepatocytes synthesize alpha 2u-globulin under androgenic regulation [4].
• Administration of dihydrotestosterone to castrated rats resulted in increased levels of alpha 2u-globulin mRNA and the amount of alpha 2u-globulin protein in the pancreatic hepatocytes [4].
• Finally, secretory proteins, rat serum albumin and alpha 2u-globulin, were localized to the lumen of the RER and to the intramembrane space between the inner and outer membranes of some of these vacuoles [5].
• The nucleotide sequence of the alpha 2u-globulin cDNA has been determined, thus elucidating the complete amino acid sequence of alpha 2u-globulin and most of the hydrophobic "leader" sequence of pro-alpha 2u-globulin [6].
• A codon usage analysis of the cDNA showed that, although all six leucine codons are used for the 14 leucine residues in mature alpha 2u-globulin, the seven leucines in the partial leader sequence reported are all encoded by the same codon, CTG [6].

Chemical compound and disease context of LOC259246

• We studied the influence of neonatal androgenization on the serum level of alpha 2u-globulin, the level of the corresponding mRNA in liver and submaxillary gland and the concentration of an androgen and oestrogen binding protein in liver cytosol [3].

Biological context of LOC259246

• Androgen-dependent synthesis of alpha 2u globulin in the rat liver has been used in our laboratory as a model for studying the effect of sex hormones on hepatic gene expression. alpha 2u Globulin is a group of low molecular weight (Mr approximately 18,000) male specific urinary proteins synthesized and secreted by hepatocytes [7].
• However, both prepubertal and senescent (greater than 800 days) male rats not only do not produce alpha 2u globulin but are also refractory to androgen administration. alpha 2u Globulin is coded by a multigene family comprising about 20-30 gene copies per haploid genome [7].
• These findings indicated that L-type and S-type mRNAs are generated by an alternative splicing mechanism in the 3' noncoding region of alpha 2u-globulin transcripts [8].
• In the liver, where a different subset of alpha 2u globulin genes is expressed, a third regulatory phenotype is observed [9].
• Three regions required for the expression of a mouse major urinary protein (MUP) transgene were identified by a deletion analysis [10].

Anatomical context of LOC259246

• When translation occurs in the presence of pancreatic microsomes this in vitro synthesized pro-alpha 2u-globulin is processed to the 19,000-dalton mature form of alpha 2u-globulin [6].
• The "prealbumin' fraction was found to correspond to alpha(2u)-globulin originating from salivary gland and the 'alpha(2)-euglobulin' fraction was identical with the major urinary protein (MUP) or alpha(2u)-globulin [11].
• Northern blot analysis confirmed the presence of 1.3 kb alpha 2u-globulin mRNA transcript in the pancreas of male rats with hepatocytes [4].
• Immunocytochemical studies indicate that the distribution of alpha 2u globulin is more homogeneous in the lachrymal gland than in the liver or submaxillary gland [9].
• MUP does not bind to hyaline droplet-inducing agents [12].

Associations of LOC259246 with chemical compounds

• The present transcriptional studies also demonstrate that administration of dexamethasone to adrenalectomized rats dramatically elevates the rate of transcription of the alpha 1-acid glycoprotein gene as well as the alpha 2u-globulin and the albumin genes, leading to elevations in alpha 1-acid glycoprotein and alpha 2u-globulin hepatic mRNA levels [1].
• Present transcriptional studies in isolated liver nuclei demonstrate that turpentine-induced acute phase mediators simultaneously enhance transcription of the alpha 1-acid glycoprotein gene and diminish transcription of albumin and alpha 2u-globulin genes; parallel alterations in the hepatic level of the corresponding mRNAs ensue [1].
• Crystals of the mouse major urinary protein (MUP) and rat alpha-2u globulin (AMG) have been grown from solutions of polyethylene glycol 3350 and CdCl2, respectively [13].
• Partial reversal of alpha 2u globulin gene expression by thyroxine in the liver of diabetic rats [14].
• The addition of 5 alpha-dihydrotestosterone to the medium perfused through livers from castrated rats resulted in a rapid increase (approximately 10-fold over the vehicle control within 120 min) in the circulating level of alpha 2u globulin [15].

Physical interactions of LOC259246

• Since estrogens strongly suppress the expression of alpha 2u-globulin genes in the rat liver, we studied the binding of estrogen-receptor complexes to fragments derived from alpha 2u-globulin gene RAO 01 using a DNA-cellulose competition assay [16].

Other interactions of LOC259246

• Amino-acid compositional and sequence analyses as well as mass spectrometric determinations of purified rat urine proteins, previously termed prealbumin and alpha(2)-euglobulin, have revealed a high homology between the two forms which have now been identified as alpha(2)-globulin species [11].
• On the basis of its immunochemical reactivity, SMP-3 (Mr = 19,500) is identified as alpha 2u-globulin while the mRNAs for SMP-1 (Mr = 28,500) and SMP-2 (Mr = 26,300) code for two yet uncharacterized proteins [17].
• However, liver-specific mRNAs such as albumin and apoprotein A-1 mRNA were expressed in normal liver and PH, but to a much lesser extent in AH60C. alpha-Fetoprotein was expressed in PH, but little in the normal liver and, if any, very little in AH60C. alpha 2u-Globulin was not expressed in either AH60C or PH [18].
• The mRNA transcript for alpha 2u-globulin declines between maturity and old age, whereas the beta-actin mRNA level remains unchanged [19].
• The weights of testes and accessory sex organs were also reinstated after supplementation with thyroxine or alpha 2u-globulin in thyroidectomized rats in comparison with thyroidectomized animals [20].

Analytical, diagnostic and therapeutic context of LOC259246

• Androgens can induce alpha 2u globulin in ovariectomized female rats in vivo and in the liver perfusion system in vitro [7].
• Orchiectomy resulted in marked decrease of alpha 2u-globulin protein and its mRNA [4].
• In situ hybridization to alpha 2u globulin RNA reveals specific signal only over the acinar cells of the lachrymal gland [9].
• Effect of thyroidectomy, and thyroxine and alpha 2u-globulin replacement therapy on testicular steroidogenic and gametogenic activities in rats [20].
• Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing [21].

References