Plasminogen is the zymogen in the circulating blood from which plasmin is formed. It is a single-chain glycoprotein with 790 amino acid residues. Activation to the active form, plasmin, by urokinase (urinary plasminogen activator) or tissue plasminogen activator (tPA) results in the formation of the 2-chain plasmin molecule held together by 2 disulfide linkages. The main function of plasmin is the digestion of fibrin in blood clots. Plasmin is a proteolytic enzyme with a specificity similar to that of trypsin.
NCBI Summary:
The protein encoded by this gene is a secreted blood zymogen that is activated by proteolysis and converted to plasmin and angiostatin. Plasmin dissolves fibrin in blood clots and is an important protease in many other cellular processes while angiostatin inhibits angiogenesis. Defects in this gene are likely a cause of thrombophilia and ligneous conjunctivitis. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]
General function
Enzyme, Hydrolase, Peptidase/Protease
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Cellular localization
Secreted
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Ovarian function
Ovulation, Steroid metabolism
Comment
Injection of antiangiogenic agents into the macaque preovulatory follicle: disruption of corpus luteum development and function. Hazzard TM et al. (2002) Ovulation and conversion of the follicle into the corpus luteum involve remarkable changes in vascular permeability and neovascularization of the luteinizing granulosa layer. To evaluate the importance of these vascular events in follicle rupture and luteal development, sequential experiments were designed in which vehicle or angiogenic inhibitors (TNP-470 or angiostatin) were injected directly into the preovulatory follicle of rhesus monkeys during spontaneous menstrual cycles. After control injections, 13 of 14 animals exhibited serum levels of progesterone (P) during the subsequent luteal phase that were comparable to untreated animals in our colony. Following low-dose (400 pg/mL) TNP-470, serum P levels increased normally until d 8 of the luteal phase, but then declined prematurely by d 9 (p < 0.05 compared to controls) and remained below controls until menses. Following high-dose (2 microg/mL) TNP-470, serum P levels were diminished in the early luteal phase (d 3-5; p < 0.05 compared to controls), but reached typical levels at mid luteal phase, only to decline prematurely by d 9 (p < 0.05) and remain low until menses. Control ovaries displayed indices of follicle rupture (protruding stigmata) and luteinization. TNP-470-treated ovaries exhibited signs of distension (torn surface epithelium/tunica albuginea) and luteinization; however, a well-formed stigmata was not observed. A "trapped" oocyte was not observed in serial sections of developing corpora lutea from control or TNP-470-treated animals. However, the early corpus luteum of TNP-470-injected ovaries contained pockets of excessive numbers of blood cells that were absent in controls. Angiostatin did not alter serum P levels or ovarian morphology compared to controls. These data suggest that acute exposure to the antiangiogenic agent TNP-470 impairs the development and functional capacity of the primate corpus luteum in a dose-dependent manner. The results are consistent with a critical role for angiogenesis in cyclic ovarian function in primates.//////////////////
Tsafriri et al. (1999) reviewed the molecular aspects of mammalian ovulation including the possible role of the plasminogen activator system. It is believed that plasmin could activate pro-collagenase to active collagenase essential for collagen breakdown during follicle rupture. Functional corpora lutea are formed in MMP inhibitor-treated plasminogen deficient mice. Wahlberg P et al. Corpus luteum (CL) formation involves dramatic tissue remodeling and angiogenesis. To determine the functional roles of the plasminogen activator (PA) and matrix metalloproteinase (MMP) systems in these processes, we have studied CL formation and function in plasminogen (plg) deficient mice, with or without treatment with the broad-spectrum synthetic MMP inhibitor galardin. Both the adult pseudopregnant (psp) CL model and the gonadotropin-primed immature mouse model were used. We found that CL formed normally not only in plasminogen deficient mice and in galardin-treated wild-type mice, but also in galardin-treated plg deficient mice, suggesting that neither of the PA and MMP systems is essential for CL formation. Nevertheless, in plg deficient mice, serum progesterone levels were reduced by approximately 50%, and the progesterone levels were not reduced further by galardin treatment. When CL from plg deficient mice were stained for several molecular markers for CL development and regression, they appeared healthy and vascularized, and were indistinguishable from CL from wild-type mice. This implies that the reduced progesterone levels were not caused by impaired CL formation. Taken together, our data suggest that neither plasmin nor MMPs, alone or in combination, are required for CL formation. The tissue remodeling and angiogenesis processes during CL formation may therefore be mediated by redundant protease systems. However, the reduced serum progesterone levels in plg deficient mice suggest that plasmin, but not MMPs, plays a role in maintenance of luteal function. This role may be performed through proteolytic activation of growth factors and other paracrine factors.
Expression regulated by
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Ovarian localization
Cumulus, Follicular Fluid
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Oocytes use the plasminogen-plasmin system to remove supernumerary spermatozoa. Coy P et al. BACKGROUNDThe role of the plasminogen-plasmin (PLG-PLA) system in fertilization is unknown, although its dysfunction has been associated with subfertility in humans. We have recently detected and quantified plasminogen in the oviductal fluid of two mammals and showed a reduction in sperm penetration during IVF when plasminogen is present. The objective of this study was to describe the mechanism by which PLG-PLA system regulates sperm entry into the oocyte.METHODS AND RESULTSBy combining biochemical, functional, electron microscopic, immunocytochemical and live cell imaging methods, we show here that (i) plasminogen is activated into the protease plasmin, by gamete interaction; (ii) urokinase-type and tissue-type plasminogen activators are present in oocytes, but they are not of cortical granule origin; (iii) sperm binding to oocytes triggers the releasing of plasminogen activators and (iv) the generated plasmin causes sperm detachment from the zona pellucida.CONCLUSIONSOur results describe a novel mechanism for the success or failure of fertilization in mammals, by which molecules present in the oviductal environment are activated by molecules originating within the gametes. We anticipate that therapeutic up- or down-regulation of this physiological mechanism may be used to help in conception or as a contraceptive tool. Since components of the PLG-PLA system are already available as drugs for heart attacks or cancer therapies, basic research on this novel function would be rapidly transferable for clinical application.
Beers (1975) reported the presence of pasminogen, plasminogen activator and proteolytic activity in bovine follicular fluid. Much of the proteolytic activity appears to be due to plasmin. In addition, plasminogen activator activity can be demonstrated in follicle wall homogenates. Evidence that plasmin decreases the tensile strength of follicle wall preparations is also reported. Plasminogen is probably not produced by ovarian cells and is derived from the general circulation. Gulamali-Majid et al. (1987) used kinetic immunonephelometry to measure concentrations of plasminogen in 53 samples of follicular fluid and the corresponding plasma from 20 women undergoing in vitro fertilization.
Follicle stages
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Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Using immature mice treated with PMSG followed by hCG to induce ovulation, Ny et al (1999) revealed that the temporal onset of follicular wall rupture (first ova observed in bursa or oviduct) was not delayed in plasminogen-deficient mice during gonadotropin-induced ovulation. However,there was a trend toward slightly reduced ovulation efficiency in the plasminogen-deficient mice. This reduction was only 13% and not statistically significant and may be connected to a delayed maturation of these mice manifested in reduced body and ovary weights. During physiological ovulation adult plasminogen-deficient mice had normal ovulation efficiency compared with plasminogen wild-type mice. The results indicate that plasmin is not required for efficient follicular rupture or for activation of other proteases involved in this process. Alternatively, the role of plasmin may be effectively compensated for by other mechanisms in the absence of plasmin. Bugge et al. (1995) reported that plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. [Romer et al. (1996) 8612226] reported impaired wound healing in mice with a disrupted plasminogen gene.
Species: human
Mutation name: None
type: naturally occurring fertility: fertile Comment:Schuster et al. (1999) reported that compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis.