James L. Hargrove's research while affiliated with Emory University and other places

Publications (15)

Article
Full-text available
In order to study whether hormone-sensitive tyrosine aminotransferase exists in tissues other than liver, we have devised means to separate the liver-specific enzyme from other enzymes that transaminate tyrosine and to distinguish between the authentic enzyme and the principal "pseudotyrosine aminotransferases," which are the isoenzymes of aspartat...
Article
We have found that butyrate selectively inhibits hormonal induction of a few specific proteins and messenger RNAs in hepatoma cells. The fatty acid salt reversibly abolishes induction of tyrosine aminotransferase by dexamethasone and dibutyryl cyclic AMP in HTC cells by inhibiting the production of tyrosine aminotransferase messenger RNA. Half-maxi...
Article
Full-text available
We have found that butyrate selectively inhibits hormonal induction of a few specific proteins and messenger RNAs in hepatoma cells. The fatty acid salt reversibly abolishes induction of tyrosine aminotransferase by dexamethasone and dibutyryl cyclic AMP in HTC cells by inhibiting the production of tyrosine aminotransferase messenger RNA. Half-maxi...
Article
The activity of the hepatic enzyme tyrosine aminotransferase (TAT) is the sum of many diverse regulatory factors. These include the developmental stage of the animal, the hormonal and nutritional environment of the animal (or tissue culture cell), other extrinsic and intrinsic regulatory cycles and factors (including cytoplasmic substances), and ch...
Article
Brief treatment of hepatoma cells in monolayer culture with concanavalin A causes a decrease in tyrosine aminotransferase specific activity that is thought to be a rapid, reversible inactivation of the enzyme (T.V. Gopalakrishnam and E.B. Thompson 1977 J. Biol. Chem. , 2717–2725). We confirm this decrease, but attribute it to an increased leakage o...
Article
The following evidence suggests that inhibition of hepatoma cell (HTC) growth by cyclic nucleotides is an adenosine-like effect that is greatly modified by the type and treatment of serum used in the culture medium and is probably not mediated by cyclic AMP-dependent protein kinase: 1) Heating serum reduces its phosphodiesterase content, thereby sl...
Article
In primary rat hepatocyte cultures, growth hormone was shown to depress tyrosine aminotransferase levels induced with hydrocortisone. Both induction by glucocorticoid and repression by growth hormone could be demonstrated in cultures several days old.
Article
A lysosomal enzyme first termed "convertase", and now cathepsin T [Gohda, E., & Pitot, H. C. (1981b) J. Biol. Chem. 256, 2567], that generates the multiple forms of tyrosine aminotransferase has been characterized with respect to its action on various proteins. When cathepsin T was incubated with highly purified tyrosine aminotransferase I, tyrosin...
Article
Full-text available
The native and one of the modified forms of tyrosine aminotransferase were purified from rat liver and characterized. Several hydrodynamic properties of the native enzyme are: Stokes radius, 46 A; subunit isoelectric point, 5.6; sedimentation coefficient, 5.6 S, frictional ratio, 1.44; diffusion coefficient, 4.65 X 10(-7) cm2 s-1; extinction coeffi...
Article
Dibutyryl cyclic AMP induces tyrosine aminotransferase significantly in several lines of cultured cells derived from either normal rat liver or hepatomas even when glucocorticoids are not present in the culture medium. Preincubation of the cells with glucocorticoids, however, markedly augments the subsequent response to the cyclic nucleotide. The a...
Article
A procedure that provides a homogeneous, native form of tyrosine aminotransferase (l-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) from rat liver in exceptionally high yield is described. This goal is accomplished by rapidly inactivating the lysosomal converting factor that generates two additional, lower-molecular-weight forms of tyrosine...
Article
Tyrosine aminotransferase messenger RNA has been translated in a cell-free system derived from rabbit reticulocytes. Cytoplasmic poly(A)-containing RNA from rat liver was used as the source of the messenger RNA. The newly synthesized subunits of the enzyme were isolated by immunoprecipitation and identified and quantitated using polyacrylamide gel...

Citations

... Chan et al. (16) at Baylor College of Medicine showed that estrogen and progesterone induce the mRNAs that encode avidin and ovalbumin, respectively, in chick oviduct. Subsequently, three groups, including ours, used different in vitro translation systems to demonstrate that glucocorticoid hormones cause proportionate increases in mRNA TAT activity and enzyme-specific activity in rat liver (17)(18)(19), as does dibutyryl cAMP (Bt 2 cAMP) (20). (This compound was used because, unlike cAMP, it rapidly penetrates cells.) ...
... Although the N-terminal amino acid sequences of these TyrATs have been reported 123, 311, there is no similarity between them and those of the two 7: litoralis enzymes. Initial characterization of the TyrATs from E. coli and rat liver were complicated by the occurrence of multiple active forms deriving from partial proteolysis of larger enzymes [23,32,331. These isoforms differed from their precursors in the absence of N-terminal peptides. ...
... However, the purified TAT had the same electroporetic homogeneity as the control, but its specific activity was higher at 199 than that of the control at 75 µmole/min/mg protein, respectively. The illustrated value is very much higher than those reported for the enzyme from Crithidia fasciculata (97.4 units / mg protein) (Rege, 1987) and lower than that reported by others (Hargrove & Granner, 1980) for the enzyme from rat liver (616 units / mg protein). Although the values of specific activity varied according to the source and the methods of separation and purification, it was reported that the specific activity of TAT purified from rat liver stabilized by tetracycline is 2640.9 ...
... In the field of the aspartate aminotransferases and, more generally, amongst the pyridoxal-phosphate-dependent enzymes there are a large number of known cases in which some selective tryptic cleavages in the NH2-terminal region occur: such is the case of mitochondrial (Sandmeier and Christen, 1980;Meer and Gehring, 1984) and cytosolic (Meer and Gehring, 1984;Iriarte et al., 1984) aspartate aminotransferases, tyrosine aminotransferase (Hargrove and Granner, 1981), serine hydroxymethyltransferase (Schirch et al., 1986), 4-aminobutyrate aminotransferase (Kim et al., 1984), dihydroxyphenylalanine decarboxylase (Tancini et al., 1988) and ornithine aminotransferase (Simmaco et al., 1989). ...
... However, hepatocyte cultures do not survive in medium lacking insulin, a hormone that can mimic the molecular effects of growth hormone in the liver (20). This complicates the interpretation (21), inhibition of tyrosine aminotransferase activity (22,23), and induction of microsomal 5a-reductase activity (24), glucose transport (25), malic enzyme (23), and specific unidentified proteins (26,27). A more serious problem is that not all forms of liver cytochrome P-450, including P-450i, are expressed in our standard hepatocyte cultures (13). ...
... Other cysteine cathepsins have been previously described; in fact, chromatography-aided molecular weight profiling showed that cathepsin J has a molecular weight of 230,000 [10]. Similarly, more archaic data characterized Cathepsins A, T, and Y [11][12][13]. Nonetheless, of all the cathepsins stated above, cathepsin B is the most intriguing, due to its core role in health and diseases [14]. It is a cysteine protease that performs a significant role in metalloproteinases regulation and it is structurally comparative to the papaya enzyme papain [15]. ...
... 14,15 Autotaxin, yet another structurally related nucleotide pyrophosphatase, has been isolated as a secreted cytokine that stimulates both chemotactic and chemokinetic responses in tumor cells. 16 The effect of autotaxin is blocked by pertussis toxin, providing a link to G-protein-mediated signaling. ...
... Our data for the Cyp2c23 promoter, suggesting that glucocorticoids associate with alterations in DNA methylation that may facilitate gene transcription are in agreement with previous studies showing that glucocorticoids induce demethylation of the hepatic tyrosine aminotransferase gene promoter in late gestation, which is permissive for transcription factor binding 17 and the induction of transcription in early postnatal life in response to hypoglycemia. 18 However, glucocorticoids both stimulate and repress gene transcription, 19 so that both decreases and increases in DNA methylation might be expected to occur as a consequence of glucocorticoid exposure. Thus, in contrast to the decrease in DNA methylation observed at the Cyp2c23 promoter, increased methylation was observed in association with repression of transcription, most notably at the erythroid-specific promoter of Alad. ...
... Our results identified 3 pathways related to amino acids, phenylalanine metabolism, tyrosine metabolism, and biosynthesis of amino acids pathways, that were affected by heat stress in UVJ tissues containing SSTs (Table 4). Tyrosine aminotransferase (TAT), which catalyzes the transamination of tyrosine to p-hydroxyphenylpyruvate (Hargrove and Mackin, 1984), was commonly involved in all 3 pathways. Avian TAT is primarily expressed in the liver and reproductive organs, including the testes, oviducts, and ovaries (Lim and Song, 2016). ...
... The data described in this report are consistent with the model that ISG transcription depends on HDAC activity to facilitate the transition from committed initiation to processive elongation through, at least in part, the targeted recruitment of P-TEFb to ISG promoter-proximal regions mediated by the Brd4 protein, and that sequestration of Brd4 by acetylated chromatin impairs ISG expression (Fig. 6 F). Previous reports have substantiated a requirement of HDAC activity for IFN-stimulated transcription (Génin et al., 2003;Nusinzon and Horvath, 2003;Chang et al., 2004;Sakamoto et al., 2004), and this observation has been extended to additional inducible expression systems, such as in response to IFN-γ (Zupkovitz et al., 2006), glucocorticoids (Tichonicky et al., 1981;Plesko et al., 1983;Bresnick et al., 1990;Mulholland et al., 2003;Kadiyala et al., 2013) or in STAT5-dependent transcription (Rascle et al., 2003;Xu et al., 2003). Broad requirement for HDAC activity during acute induction of gene expression from stimulus-dependent promoters suggests a common positive role for HDAC enzymes for this subset of genes, in addition to its well-appreciated repressive role of maintaining histone deacetylation on silent chromatin. ...