Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypophysectomized rats were treated for 6 days with 200 mug per day of either human chorionic somatomammotropin, human pituitary growth hormone, plasmin-modified human pituitary growth hormone, or ovine prolactin. All hormone preparations except ovine prolactin enhanced the ability of the pancreases of hypophysectomized rats to secrete insulin in the isolated pancreas perfusion system.
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PMID:Enhancement of insulin secretion by human chorionic somatomammotropin and related hormones. 13 69

The reduction and alkylation of the two disulfide bonds in a preparation of human pituitary growth hormone which had been previously modified by limited proteolysis with the enzyme plasmin have been studied. Quantitative and selective reduction of the carboxyl-terminal disulfide, as well as total reduction of both disulfides, has been achieved in the absence of denaturants. Circular dichroism spectra of the various reduced and reduced-alkylated derivatives have provided sufficient information to allow an estimation of the individual contributions of each disulfide bond to the total optical activity of the protein. These contributions were found to represent a significant portion of the total optical activity between 290 and 250 nm. The carboxyl-termimal bond exhibits negative dichroism with an apparent center near 258 nm ([theta]M,258nm = 2100 deg cm2 dmol-1). By comparison, the contribution of the remaining disulfide is red-shifted to 273 nm, is also negative in sign, and somewhat more intense ([theta]M,273nm = 3200 deg cm2 dmol-1). Circular dichroism measurements have also been used to approximate the rate of reduction of the protein.
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PMID:Optical activity of disulfide bonds in proteins. 1. Studies on plasmin modified human somatotropin. 13 32

The contributions of the homologous carboxyl-terminal disulfide bonds in human choriomammotropin (human chorionic somatomammotropin, human placental lactogen) and bovine somatotropin (pituitary growth hormone), to the near ultraviolet circular dichroism spectra of these two proteins have been evaluated. The disulfide bond in the human placental protein displays a broad, negative band centered near 260 nm ([theta]M, 260nm = -2100 +/- 160 deg cm2 dmol-1) which is equivalent, within experimental error, to the band previously assigned to the identical disulfide in plasmin modified human somatotropin. The homologous disulfide in the bovine hormone also exhibits a negative band, very similar in intensity ([theta]M, 254nm = -2200 +/- 210 deg cm2 dmol-1), with an estimated band center blue-shifted relative to the human proteins to 252-255 nm. Reoxidation of either partially reduced protein results in complete repair of the circular dichroism spectrum to that of the native protein. No definite contributions could be assigned below 240 nm to the optical activity of these disulfide bonds. Circular dichroism measurements have also been used to approximate the rates of reduction of the two proteins.
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PMID:Optical activity of disulfide bonds in proteins: studies on human choriomammotropin and bovine pituitary somatotropin. 91 64

Somatotropin exerts a powerful galactopoietic effect when it is administered to dairy cattle. The mechanism by which somatotropin increases milk yield is currently unknown. This study describes the relationship between long-term exogenous somatotropin injections, milk plasmin concentrations, and milk yield. Plasmin is a serine-protease involved in rodent mammary gland involution. Thirty-five control cows were shown to increase milk plasmin concentrations and decrease milk yield as their lactation period advanced past the 2nd mo. In 42 somatotropin injected cows, milk plasmin was maintained at low concentrations, and milking performance was enhanced. Cessation of somatotropin injections at drying off led to a rapid elevation of milk plasmin to control values. Our hypothesis is that somatotropin suppresses plasmin production within the mammary gland, thereby suppressing involution and allowing a persistence of milk production. During a normal lactation, gradually increasing amounts of plasmin within the mammary gland results in the gradual involution process.
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PMID:Effect of somatotropin on the plasminogen and plasmin system in the mammary gland: proposed mechanism of action for somatotropin on the mammary gland. 214 11

We have previously demonstrated that IGFBP-5 production by mammary epithelial cells increases dramatically during involution of the mammary gland. To demonstrate a causal relationship between IGFBP-5 and cell death we created transgenic mice expressing IGFBP-5 in the mammary gland using a mammary-specific promoter, beta-lactoglobulin. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Histological analysis indicated reduced numbers of alveolar end buds, with decreased ductal branching. Transgenic dams produced IGFBP-5 in their milk at concentrations similar to those achieved at the end of normal lactation. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. BrdU labelling was decreased, whereas DNA ladders were increased in transgenic animals on day 1 of lactation. On day 2 postpartum, the epithelial invasion of the mammary fat pad was clearly impaired in transgenic animals. The concentrations of the pro-apoptotic molecule caspase-3 and of plasmin were both increased in transgenic animals whilst the concentrations of 2 prosurvival molecules Bcl-2 and Bcl-x(L)were both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I we examined IGF receptor phosphorylation and Akt phosphorylation and showed that both were inhibited. We attempted to "rescue" the transgenic phenotype by using growth hormone to increase endogenous IGF-I concentrations or by implanting minipumps delivering an IGF-1 analogue, R(3)-IGF-1, which binds weakly to IGFBP-5. Growth hormone treatment failed to affect mammary development suggesting that increased concentrations of endogenous IGF-1 are insufficient to overcome the high concentrations of IGFBP-5 produced by these transgenic animals. In contrast mammary development (gland weight and DNA content) was normalised by R3-IGF-I although milk production was only partially restored. This is the first demonstration that over-expression of IGFBP-5 can lead to; impaired mammary development, increased expression of the pro-apoptotic molecule caspase-3, increased plasmin generation and decreased expression of pro-survival molecules of the Bcl-2 family. It clearly demonstrates that IGF-I is an important developmental/survival factor for the mammary gland and, furthermore, this cell death programme may be utilised in a wide variety of tissues.
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PMID:Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. 1222 11