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tissue plasminogen activator

 
Dictionary: tissue plasminogen activator
 

n. (Abbr. TPA or tPA)
  1. A clot-dissolving enzyme that is produced naturally by cells in the walls of blood vessels and catalyzes the conversion of plasminogen to plasmin.
  2. A preparation of this enzyme that is produced by genetic engineering and used to dissolve clots blocking coronary arteries in heart attack and cranial arteries in certain cases of stroke.

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Wikipedia: Tissue plasminogen activator
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Plasminogen activator, tissue
PDB rendering based on 1a5h.
Available structures: 1a5h, 1bda, 1pk2, 1pml, 1rtf, 1tpg, 1tpk, 1tpm, 1tpn
Identifiers
Symbols PLAT; DKFZp686I03148; T-PA; TPA
External IDs OMIM: 173370 MGI97610 HomoloGene717
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 5327 18791
Ensembl ENSG00000104368 ENSMUSG00000031538
Uniprot P00750 Q6P7U0
Refseq NM_000930 (mRNA)
NP_000921 (protein)
NM_008872 (mRNA)
NP_032898 (protein)
Location Chr 8: 42.15 - 42.18 Mb Chr 8: 24.22 - 24.25 Mb
Pubmed search [1] [2]


Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. Specifically, it is a serine protease (EC 3.4.21.68) found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat stroke.

Contents

Function

A simplified illustration demonstrates clot breakdown (fibrinolysis), with blue arrows denoting stimulation, and red arrows inhibition.

The classic role of tPA is in the clotting system. Specifically, tPA catalyzes the conversion of plasminogen into plasmin. It does so by cleaving the single-chained plasminogen into two chains. These two chains are linked by a disulfide bond and the resulting molecule is called plasmin.

Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding. Decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.

Tissue plasminogen activator also plays a role in cell migration and tissue remodeling.

Genetics

Tissue plasminogen activator is a protein encoded by the PLAT gene, which is located on chromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

Recombinant tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction and stroke. To be effective, tPA must be administered within the first three hours of the event to be given intravenously, or within six hours to be administered through an arterial catheter directly to the site of occlusion. The guideline in Ontario, Canada hospitals for ischemic strokes is that tPA must be given within 3 hours of the onset of symptoms. Because of this, only about 3% of patients qualify for this treatment. tPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use.

Recently tPA has been used to dissolve thrombi associated with ischemic strokes and brain injury.

In addition, people with frostbite that were treated with tPA had fewer amputations than those that were not.[1]

In tPA overdose, aminocaproic acid works as an antidote.[2]

See also

References

  1. ^ Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR (June 2007). "Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy". Arch Surg 142 (6): 546–51; discussion 551–3. doi:10.1001/archsurg.142.6.546. PMID 17576891. 
  2. ^ Quizlet > Toxins and Antidotes

Further reading

  • Rijken DC (1988). "Relationships between structure and function of tissue-type plasminogen activator". Klin. Wochenschr. 66 Suppl 12: 33–9. PMID 3126346. 
  • Bode W, Renatus M (1998). "Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function". Curr. Opin. Struct. Biol. 7 (6): 865–72. doi:10.1016/S0959-440X(97)80159-5. PMID 9434908. 
  • Collen D, Billiau A, Edy J, De Somer P., Identification of the human plasma protein which inhibits fibrinolysis associated with malignant cells, Biochim Biophys Acta. 1977 Sep 29;499(2):194-201
  • Anglés-Cano E, Rojas G (2003). "Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site". Biol. Chem. 383 (1): 93–9. doi:10.1515/BC.2002.009. PMID 11928826. 
  • Ny T, Wahlberg P, Brändström IJ (2003). "Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems". Mol. Cell. Endocrinol. 187 (1-2): 29–38. doi:10.1016/S0303-7207(01)00711-0. PMID 11988309. 
  • Teesalu T, Kulla A, Asser T, et al. (2002). "Tissue plasminogen activator as a key effector in neurobiology and neuropathology". Biochem. Soc. Trans. 30 (2): 183–9. doi:10.1042/ (inactive 2008-06-21). PMID 12023848. 
  • Pang PT, Lu B (2005). "Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF". Ageing Res. Rev. 3 (4): 407–30. doi:10.1016/j.arr.2004.07.002. PMID 15541709. 
  • Sheehan JJ, Tsirka SE (2005). "Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review". Glia 50 (4): 340–50. doi:10.1002/glia.20150. PMID 15846799. 

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