Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular ATP stimulated histamine release and generation of leukotrience C4 (LTC4) accompanied with the formation of inositol phosphates and a rapid increase in intracellular Ca2+ ([Ca2+]i) in mouse bone marrow-derived cultured mast cells (BMMC). The rank order of histamine-releasing potency of ATP and its metabolites is ATP greater than ADP greater than AMP greater than adenosine. Nonhydrolyzable ATP analog, adenosine-5'-O-[2-thiotriphosphate] (ATP-S) released more histamine from the cells than ATP. On the other hand, simultaneous addition of adenosine analogues at micromolar concentrations potentiated histamine release from the cells induced by ATP (50 microM) or DNP-HSA antigen (0.1 ng/ml) in the following rank order: adenosine greater than AMP much greater than ADP = ATP. Histamine release potentiated by adenosine was blocked by the treatment with pertussis toxin, whereas histamine release induced by ATP was not affected by the toxin, suggesting that extracellular ATP stimulate histamine release from BMMC probably via mechanisms independent of the potentiation of histamine release induced by adenosine.
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PMID:The stimuli releasing histamine from murine bone marrow-derived mast cells. 2. Mechanisms involved in histamine release induced by extracellular ATP and its metabolites. 171 46

CKS-17, an immunosuppressive peptide homologous to certain retroviral transmembrane envelope protein, has been shown to inhibit lymphocyte proliferation in response to mitogens or alloantigens when covalently attached to bovine serum albumin (CKS-17-BSA). To define its site of action, we determined if CKS-17 conjugated to human serum albumin (CKS-17-HSA) could block the direct activation of lymphocytes by phorbol-12-myristate-13-acetate (PMA) or by a synthetic diacylglycerol, dioctanoylglycerol (DiC8). CKS-17-HSA inhibited lymphocyte proliferation in response to PMA and ionomycin in a dose-dependent manner with up to 88% inhibition occurring with 15 microM CKS-17-HSA. The conjugated peptide also inhibited the proliferation of lymphocytes in response to DiC8 and ionomycin by up to 57% at 15 microM CKS-17-HSA. Based on these findings we investigated the effect of CKS-17-HSA on the activity of protein kinase C (PKC), an enzyme directly activated by PMA and DiC8. PKC was isolated chromatographically from the cytosol of human neutrophils or the human lymphoblastoid cell line Jurkat. CKS-17-HSA caused a dose-dependent enzyme inhibition with a concentration giving half-maximal inhibition (IC50) of ca.3 microM and greater than 95% inhibition at 15 microM CKS-17-HSA. Inhibition of PKC by the conjugated peptide was not reversed by increasing concentrations of Ca2+, Mg2+, phosphatidylserine, diolein, or adenosine triphosphate (ATP), indicating that the conjugated peptide did not function as a chelator or competitive inhibitor. In contrast to its effects on PKC, CKS-17-HSA did not inhibit the activity of adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase (PK-A) nor the calcium and phospholipid-independent form of PKC (PK-M). Moreover the peptide inhibited in vivo PKC activity in cytosol of intact cells and in membrane of PMA-stimulated cells. These results suggest that the inhibition of lymphocyte proliferation by CKS-17-HSA may be due to the direct inactivation of PKC.
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PMID:A synthetic peptide homologous to retroviral transmembrane envelope proteins depresses protein kinase C mediated lymphocyte proliferation and directly inactivated protein kinase C: a potential mechanism for immunosuppression. 192 61

In plasma of mice injected with adenine-9-beta-D-arabinofuranoside monophosphate (ara-AMP) coupled to human lactosaminated serum albumin (L-HSA) some of the ara-AMP molecules are enzymatically released, whereas others remain linked to L-HSA. Evidence has been obtained that ara-AMP is not deaminated when it is conjugated to L-HSA, in contrast to the free drug which is rapidly metabolized to its hypoxanthine derivative.
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PMID:A study on the pharmacokinetics in mouse of adenine-9-beta-D-arabinofuranoside 5-monophosphate conjugated with lactosaminated albumin. 241 78

9-beta-D-Arabinofuranosyladenine 5'-monophosphate (ara-AMP) coupled to lactosaminated human albumin (L-HSA), injected i.v. into rats, selectively enters the liver. The conjugate concentration in parenchymal and sinusoidal hepatic cells, isolated by collagenase perfusion, was found to be practically equal in both cell types. This indicates that the high uptake of L-HSA-ara-AMP complex by the whole liver also corresponds to a high conjugate concentration in hepatocytes where ara-AMP should be targeted in order to increase its chemotherapeutic index in chronic hepatitis B treatment.
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PMID:Distribution of a conjugate of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin in parenchymal and sinusoidal cells of rat liver. 244 May 49

Leukotriene C and D markedly enhanced plasma exudation in rat skin, using [131I]-labeled human serum albumin ([131I]-HSA) to measure vascular permeability. The adenylate cyclase activator forskolin only slightly increased plasma exudation, while markedly potentiating the leukotriene response. Prostaglandin E1 increases plasma exudation in rat skin, but appears to act by a different mechanism than leukotrienes, since the responses to combinations of prostaglandin and leukotrienes are synergistic and the responses to prostaglandins are inhibited by forskolin. The phosphodiesterase inhibitor, isobutylmethylxanthine also potentiated the leukotriene C-induced response. The effects of the various agents on leukotriene responses are similar to effects of these agents on bradykinin and histamine-induced plasma exudation. These results suggest that an increase in the cyclic AMP in the rat skin, elicited by forskolin or prostaglandin potentiates the leukotriene C and D-induced plasma exudation and that leukotriene C and D increase the vascular permeability through the same type of mechanism that pertains for histamine and bradykinin.
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PMID:Effects of forskolin and prostaglandin E1 on leukotriene C- and D-induced plasma exudation in the rat skin. 373 23

We covalently coupled 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) to the carrier molecule lactosaminated human serum albumin using a water-soluble carbodiimide with a two-step conjugation method (pH 4.5 and pH 7.5) instead of the commonly used single-step conjugation at pH 7.5. This resulted in a predominantly monomeric conjugate (lac27-HSA-ara-AMP9). The conjugate was stable in buffer (pH 7.4) and blood plasma. After in vivo injection, the carrier and the monomeric conjugate were subjected to selective endocytosis in rat hepatocytes, as shown on immunohistochemical study and cell-separation techniques using 125I-labeled material. In competition experiments with other ligands for the asialoglycoprotein receptor N-acetylgalactosamine and asialofetuin, we showed that both lactosaminated human serum albumin and lac27-HSA-ara-AMP9 are subject to endocytosis by this receptor system. Although the coupling of ara-AMP significantly increased the net negative charge of the conjugate compared with the native carrier, liver uptake was not affected by coadministration of an excess of succinylated human serum albumin (suc-HSA), a negatively charged ligand for the scavenger receptor. Incubation studies with purified rat liver lysosomes showed that in this acidic and proteolytic environment, mainly ara-AMP and, to a much lesser extent, ara-A itself were released from the carrier. After injection into the rat in vivo and in isolated perfused rat liver, no free ara-AMP or 9-B-D-arabinofuranosyladenine (ara-A) could be detected in plasma and perfusate, respectively, indicating proper retention of the virally active components in hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coupling of the antiviral drug ara-AMP to lactosaminated albumin leads to specific uptake in rat and human hepatocytes. 768 77

Five genes on human chromosome 7 (HSA 7) were assigned to bovine chromosome 21 (BTA 21) and 4 (BTA 4) using a bovine-rodent somatic hybrid cell panel. These five genes were alpha-I subunit of adenylate cyclase-inhibiting G-protein (GNAI1), alpha/beta preprotachykinin (TAC1), reelin (RELN), c-AMP dependant protein kinase type II beta regulatory chain (PRKAR2B) and apolipoprotein A1 regulatory protein 1 (TFCOUP2). Four genes mapped to BTA 4 (GNAI1, TAC1, RELN, PRKAR2B) while one gene mapped to BTA 21 (TFCOUP2). This study confirms the synteny conservation between HSA 7 and BTA 4, finely maps the breakpoints of conserved synteny on HSA 7 and defines a new synteny conservation between HSA 7 and BTA 21.
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PMID:Synteny mapping of five human chromosome 7 genes on bovine chromosomes 4 and 21. 1034 25