Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant tissue-type plasminogen activator (rt-PA, alteplase, Actilyse, Activase; CAS 105857-23-6) is the most effective agent currently available for thrombolytic therapy of life-threatening diseases such as acute myocardial infarction. It acts by rapid, clot-specific lysis of pathological thrombi, with only limited effects on systemic hemostasis. Pharmacokinetics of rt-PA have been extensively characterized in animal species and man, and can be generally described by a 3-compartment model. Preferred analytical methods for rt-PA in plasma are ELISA and chromogenic activity assays. The dominant plasma half-life of rt-PA in myocardial infarction patients is short (3.6 min), which allows excellent control of plasma levels during therapy. Steady-state plasma concentrations effecting coronary thrombolysis using the current dosage regimen are 2.2 micrograms/ml. A deep compartment results in elevated rt-PA concentrations several hours after termination of infusions, which may contribute to short-term maintenance of patency of reperfused blood vessels. Clearance of rt-PA can be saturated in animals at very high plasma concentrations (Km = 12-15 micrograms/ml), however, pharmacokinetics in clinical settings are linear. Clearance occurs via hepatic receptor mediated endocytosis and intracellular degradation in liver parenchymal, endothelial and Kupffer cells. The catabolism involves coated pits, coated vesicles, endosomes, and finally degradation in lysosomes. Current evidence supports the existence of hepatic receptors recognizing carbohydrate as well as polypeptide determinants in rt-PA. In conclusion, increasing knowledge of rt-PA pharmacokinetics will contribute to the optimization of new clinical dosage regimens, such as front-loaded infusions and boluses, and to the identification of novel molecular targets for pharmacologic control of rt-PA catabolism and of circulating fibrinolytic activity.
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PMID:Pharmacokinetics and hepatic catabolism of tissue-type plasminogen activator. 181 34

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) activase mRNA and protein synthesis were measured in the leaves of cotton (Gossypium hirsutum L.) plants under control (28 degrees C) or heat-stress (41 degrees C) conditions. A decline in activase transcript abundance occurred rapidly during the photoperiod and was unaffected by heat stress. In response to high temperature, de novo protein synthesis rapidly shifted from mainly expression of Rubisco large and small subunits to the major heat-shock proteins, while de novo synthesis of the constitutively expressed 47- and 43-kDa activase polypeptides was not appreciably altered. However, heat stress induced the synthesis of a 46-kDa polypeptide that immunoprecipitated with antibodies monospecific to activase. Expression of the 46-kDa polypeptide ceased within 1 h of the return of heat-stressed plants to control conditions. Activase precursors of 55 and 51 kDa were detected among the in vitro translation products of RNA from control and heat-stressed plants. In addition, a 53-kDa polypeptide that also immunoprecipitated with anti-activase IgG was among the in vitro translation products of RNA from heat-stressed plants. This putative activase precursor did not occur among the in vitro translation products of RNA from plants that had recovered from heat stress. The levels of the constitutive 47- and 43-kDa activase polypeptides were similar in control and heat-stressed plants, based on immunoblotting with antibodies to activase. However, a 46-kDa cross-reacting polypeptide was also present in heat-stressed plants and constituted about 5% of the total activase after 48 h at high temperature. The identity of the heat-induced 46-kDa polypeptide as activase was confirmed by protein sequencing, which showed that its N-terminal sequence was identical to that of the constitutive 47-kDa activase polypeptide. The presence of multiple isoforms for both the 47- and 43-kDa activase polypeptides on immunoblots of two-dimensional gels and the complex banding pattern on Southern blots together suggest the existence of more than one activase gene and the possibility that the synthesis of the heat-induced activase polypeptide may be regulated transcriptionally. Induction of a new form of activase may constitute a mechanism of photosynthetic acclimation to heat stress in cotton.
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PMID:Heat stress induces the synthesis of a new form of ribulose-1,5-bisphosphate carboxylase/oxygenase activase in cotton leaves. 1176 61