Biomaterial Database

Manipulation of thromboxane synthesis by novel 26,27-dialkyl analogues of 1 alpha,25-dihydroxyvitamin D3 in human promyelocytic leukemia (HL-60) cells. 1992

A Honda, and Y Mori, and N Ikekawa, and A Raz

Department of Biochemistry, Tokyo College of Pharmacy, Japan.

Using new steroidal side-chain-lengthened 26,27-dialkyl analogues of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3], we manipulated the synthesis of thromboxane and thromboxane-producing enzymes, cyclo-oxygenase and thromboxane synthase, in human promyelocytic leukemia (HL-60) cells in serum-free culture. The order of potency of the analogues for stimulating thromboxane B2 synthetic activity from arachidonic acid (reflecting combined cyclo-oxygenase activity and thromboxane synthase activity) and from prostaglandin H2 (thromboxane synthase activity only) as well as for cyclo-oxygenase induction was 1 alpha,25-(OH)2D3 > or = 1 alpha,25-(OH)2-26,27-CH3)2D3 > 1 alpha,25-(OH)2-26,27-(C2H5)2D3 >> 1 alpha,25-(OH)2-26,27-(C3H7)2D3. These results suggest that there are functional and structural limits to the chain length of C-26 and C-27 dialkyl groups flanking the C-25-OH group in the 1 alpha,25-(OH)2D3 molecule for expressing thromboxane synthetic activity in HL-60 cells. Removal of the C-1 alpha-OH group from 1 alpha,25-(OH)2D3 led to markedly decreased thromboxane synthetic activity in HL-60 cells. These structure-activity relationships indicate that both the C-25-OH and C-1 alpha-OH groups in the 1 alpha,25-(OH)2D3 molecule are essential for expressing thromboxane synthesis in HL-60 cells. Also, the rank order for stimulating thromboxane synthesis correlated well with the binding affinity of these dialkyl analogues for the 1 alpha,25-(OH)2D3 receptor of HL-60 cells, suggesting a 1 alpha,25-(OH)2D3 receptor-mediated induction mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D011233	Precipitin Tests	Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.	Precipitin Test,Test, Precipitin,Tests, Precipitin
D011451	Prostaglandin-Endoperoxide Synthases	Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.	Fatty Acid Cyclo-Oxygenase,PGH Synthase,Prostaglandin H Synthase,Prostaglandin Synthase,Prostaglandin-Endoperoxide Synthase,Arachidonic Acid Cyclooxygenase,Cyclo-Oxygenase,Cyclooxygenase,Cyclooxygenases,Hydroperoxide Cyclase,PGH2 Synthetase,Prostaglandin Cyclo-Oxygenase,Prostaglandin Cyclooxygenase,Prostaglandin Endoperoxide Synthetase,Prostaglandin G-H Synthase,Prostaglandin H2 Synthetase,Prostaglandin Synthetase,Cyclase, Hydroperoxide,Cyclo Oxygenase,Cyclo-Oxygenase, Fatty Acid,Cyclo-Oxygenase, Prostaglandin,Cyclooxygenase, Arachidonic Acid,Cyclooxygenase, Prostaglandin,Endoperoxide Synthetase, Prostaglandin,Fatty Acid Cyclo Oxygenase,G-H Synthase, Prostaglandin,Prostaglandin Cyclo Oxygenase,Prostaglandin Endoperoxide Synthases,Prostaglandin G H Synthase,Synthase, PGH,Synthase, Prostaglandin,Synthase, Prostaglandin G-H,Synthase, Prostaglandin H,Synthase, Prostaglandin-Endoperoxide,Synthases, Prostaglandin-Endoperoxide,Synthetase, PGH2,Synthetase, Prostaglandin,Synthetase, Prostaglandin Endoperoxide,Synthetase, Prostaglandin H2
D011987	Receptors, Steroid	Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.	Corticosteroid Receptors,Receptors, Corticosteroid,Steroid Receptors,Corticosteroid Receptor,Receptors, Steroids,Steroid Receptor,Receptor, Corticosteroid,Receptor, Steroid,Steroids Receptors
D002117	Calcitriol	The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.	1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004591	Electrophoresis, Polyacrylamide Gel	Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.	Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013929	Thromboxane B2	A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).	B2, Thromboxane