Disease relevance of histidinol

• These experiments demonstrated that L-histidinol not only protected the marrow cell population from both ara-C and FUra, but also increased significantly the toxicities of these agents for the intrafemoral tumor cells [1].
• The effects of L-histidinol, a structural analog of the essential amino acid L-histidine, on the proliferative responses and anticancer drug vulnerability of cultured spleen cells from male C57BL/6J mice exposed to optimal mitogenic doses of concanavalin A (Con A) or E. coli lipopolysaccharide (LPS) were investigated [2].
• Simultaneously, the inclusion of L-histidinol provided a statistically significant increase in the capacity of these two anticancer drugs to eradicate intraperitoneal mastocytoma cells [3].
• In contrast, both L1210 leukemia cells and colon 26 adenocarcinoma cells were more efficiently killed by combinations of L-histidinol and cisplatin [4].
• However, in contrast to results reported in the L1210 leukemic system, L-histidinol also reduced the cytotoxic activity of FUra against CD8F1 breast tumors [5].

High impact information on histidinol

• Five of seven histidinol-resistant clones and three of three G418-resistant clones generated germ-line chimeras [6].
• Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near the 5' exons of expressed genes, including one in the developmentally regulated REX-1 gene [6].
• We showed previously that the transcript from an actin-HIS4 gene fusion containing the mutation TACTAAC to TACTACC (designated C259) is spliced inefficiently, thereby preventing growth on the histidine precursor histidinol [7].
• By selecting for growth on histidinol, we have identified a mutant in which the splicing of the C259 transcript is increased fourfold; splicing of other mutated introns is not significantly improved [7].
• Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy [8].

Chemical compound and disease context of histidinol

• The toxicity of cisplatin was prevented only when cisplatin was given before L-histidinol [4].
• We report also that the histidinol-mediated protection to bone marrow cells persists in L1210 leukemia-bearing DBA/2J mice treated with combinations of histidinol and 1-beta-D-arabinofuranosylcytosine or 5-fluorouracil without diminishing the toxicities of these agents for in situ leukemia cells [9].
• Structural Snapshots of Escherichia coli Histidinol Phosphate Phosphatase along the Reaction Pathway [10].
• Crystal structure of histidinol phosphate aminotransferase (HisC) from Escherichia coli, and its covalent complex with pyridoxal-5'-phosphate and l-histidinol phosphate [11].
• The efficiency of transducing histidinol resistance was 2,500-fold lower than the efficiency of transducing neomycin resistance when the neomycin phosphotransferase gene was located within the retrovirus and expressed from an independent promoter [12].

Biological context of histidinol

• Flow cytometric analysis of randomly proliferating P815 mastocytoma cells revealed that although exposure to L-histidinol did not preclude cells from traversing the cell cycle, the analogue nonetheless conferred a dose-dependent and apparently nonspecific delay of cell cycle transit [3].
• Reversal of the multidrug-resistant phenotype of Chinese hamster ovary cells by L-histidinol [13].
• Quantitative cell survival assays of murine bone marrow cells and of clonogenic tumor cells obtained from treated animals demonstrated that L-histidinol eliminated the bone marrow toxicity otherwise attending the use of the drugs ara-C and FUra [3].
• Expression of the cDNA clone in an E. coli his operon deletion strain rendered the mutant able to grow in the presence of histidinol [14].
• The virus contains a selectable gene encoding histidinol dehydrogenase (his) in the U3 region of the 3' long terminal repeat (LTR) [15].

Anatomical context of histidinol

• Histidinol-mediated enhancement of the specificity of two anticancer drugs in mice bearing leukemic bone marrow disease [1].
• The differential S-phase drug sensitivity mediated by histidinol and theophylline persisted under cocultivation conditions, thereby allowing the selective and total eradiction of colonies of HeLa cells in the presence of subconfluent HFF cells [16].
• These responses of cultured murine lymphocytes to L-histidinol provided dramatic and extended protection from the cell cycle phase-specific drug cytosine arabinoside and dramatic but transient protection from the cell cycle-specific drug 5-fluorouracil [2].
• The effects of L-histidinol on the susceptibility of the transplantable murine mast-cell neoplasm P815 mastocytoma to selected anticancer drugs have been evaluated on cells growing in culture and in syngeneic DBA/2J mice [3].
• The histidinol-resistant cell lines had an increase in translatable polyadenylated mRNA for histidyl-tRNA synthetase [17].

Associations of histidinol with other chemical compounds

• The his4 region of yeast encodes the information for the third (phosphoribosyl-AMP cyclohydrolase), second (phosphoribosyl-ATP pyrophosphohydrolase), and tenth (histidinol dehydrogenase) steps in the histidine biosynthetic pathway [18].
• The seventh step in the synthesis of histidine within eubacteria is carried out by a pyridoxal-5'-phosphate (PLP)-dependent l-histidinol phosphate aminotransferase (HisC, EC 2.6.1.9) [11].
• To test whether L-histidinol is more beneficial for selection of keratinocytes than G418, we constructed two retroviral vectors that contain both the neo and the histidinol dehydrogenase (hisD) genes [19].
• Previous isotope exchange results had suggested that the oxidation of histidinol to the intermediate histidinaldehyde occurred 2-3-fold more rapidly than overall catalysis [20].
• The inactivation followed pseudo-first-order kinetics and was prevented by low concentrations of the substrate L-histidinol or by the competitive inhibitors histamine and imidazole [21].

Gene context of histidinol

• With the CYC1 fragment cloned in its wild-type (forward) orientation within the actin intron, transformants cannot grow on histidinol, whereas cells transformed with the vector carrying the reverse orientation of this fragment are able to grow well [22].
• Histidine limitation in the presence of histidinol induced a twofold increase in the phosphorylation of eIF2alpha and a concomitant reduction in eIF2B activity in perfused livers from wild-type mice, but no changes in livers from Gcn2(-/-) mice [23].
• Nucleotide and amino acid polymorphism in the gene for L-histidinol dehydrogenase of Escherichia coli K12 [24].
• Two classes of mutations were obtained: (i) those that altered the coding region of HOL1, conferring the ability to take up histidinol; and (ii) cis-acting mutations (selected in a mutant HOL1-1 background) that increased expression of the Hol1 protein [25].
• The crystal structures of HisRS from two organisms and their complexes with histidine, histidyl-adenylate and histidinol with ATP have been solved [26].

Analytical, diagnostic and therapeutic context of histidinol

• Southern blot analysis of wild-type and histidinol-resistant cells with this cDNA showed that the histidyl-tRNA synthetase DNA bands were amplified in the resistant cells [17].
• Immunoprecipitation of [35S]methionine-labeled cell lysates with antibodies to histidyl-tRNA synthetase showed increased synthesis of the enzyme in histidinol-resistant cells [17].
• The transgenic embryonic fibroblasts survive under a wide range of histidinol-containing growth conditions and support growth of ES cell cultures [27].
• Gel filtration analysis indicate the aromatic and histidinol phosphate aminotransferases have molecular weights of 63,500 and 33,000, respectively [28].
• Analysis of individual protein bands by SDS-PAGE showed that at least 17 bands became less prominent, while 13 polypeptides became more prominent, during exposure to histidinol [29].

References