fbpx
Wikipedia

Kininogen

January 01, 1970

Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems.

Types of kininogen edit

There are two main types of kininogen (KNG), high-molecular-weight-kininogen and low-molecular-weight-kininogen, with a third type – T-kininogen – only found in rats but not humans.

High molecular weight kininogen edit

High-molecular-weight-kininogen (HK) is a non-enzymatic cofactor involved in the kinin-kallikrein system, which plays a role in blood coagulation, blood pressure regulation, and inflammation. It is synthesized in endothelial cells and is produced mostly by the liver. It is also a precursor protein for bradykinin.

 
Protein structure of bradykinin. Bradykinin is a nine amino acid-long polypeptide made by the cleavage of high-molecular-weight kininogen at D4. It acts as an inflammatory mediator.

Low molecular weight kininogen edit

Low-molecular-weight-kininogen (LK) is mainly a precursor protein for kallidin. LK, however, is not actively involved in blood coagulation, but its byproducts can be later converted and introduced to the coagulation pathway.

T-kininogen edit

T-kininogen (TK) is only found in rats and a protein whose function is still being researched. TK is believed to be a biological indicator of senescence in rats,[1] which can be measured by the level of endothelial cell production during the aging process.[2]

Structure edit

HK consists of 644 amino acid residues, which are separated into six different domains.[3] Domains 1, 2, and 3 are called the “heavy chain” with Domains 2 and 3 having cysteine protease activity.[4] Domains 5 and 6 are called the “light chain,” both of which bind specific molecules: Domain 5 binds heparin and zinc and selectively binds to anionic surfaces while Domain 6 binds prekallikrein, the protease precursor to plasma kallikrein.[5] Domain 4 connects the heavy chain and light chain together, and its cleavage at this site releases bradykinin.[6]

LK consists of 427 amino acid residues, which can also be separated into a “heavy chain” and a “light chain."[7]

T-kininogen consists of 430 amino acid residues.[8]

HK and LK are created by the alternative splicing of the same kininogen (KNG) gene, which in humans, is located at chromosome 3q27.[9] Kininogens are related to cystatins through their similar glycosylated regions.[10]

Function edit

High-molecular weight kininogen edit

During the contact activation system (CAS), also known as the intrinsic pathway, the binding of HK, factor XII (FXII), and prekallikrein (PK) to an anionic surface initiates blood coagulation and the kinin-kallikrein system through the activation of a cascade of enzymes.[11] Factor XII is a zymogen, and upon binding with tissue to the anionic surface, exhibits some protease activity, starting the enzymatic cascade.[12] Both the intrinsic and its corresponding extrinsic pathway, which is activated when outside trauma activates tissue factor (TF), an important glycoprotein, culminate in the activation of a serine protease called Factor X. Factor X is responsible for the conversion of prothrombin into an important protease in clotting called thrombin, which itself participates in the clotting cascade by activating more enzymes and proteins downstream in order to create even more thrombin.

In the kinin-kallikrein system, the proteolytic cleavage of HK by the enzyme plasma kallikrein makes bradykinin, an inflammatory mediator that can lower blood pressure by way of vasodilation. The kinin-kallikrein system plays a small role in coagulation.

 
Blood clotting cascade. The blood clotting cascade consists of the intrinsic and extrinsic pathway, both of which create thrombin, a protease involved in blood clotting. The intrinsic pathway requires kininogen, specifically high molecular weight kininogen, as a cofactor.

HK and LK are noncompetitive inhibitors of activated thrombin.[13]

Low-molecular weight kininogen edit

The proteolytical cleavage of LK by tissue kallikreins creates kallidin, which is a possible substrate for carboxypeptidase M.[14] Kallidin can be converted into bradykinin by Aminopeptidase B,[15] creating a connection between LK and the kinin-kallikrein system.

T-kininogen edit

Research has shown that T-kininogen is a possible biomarker for senescence within rats.[1]

Disease and medical relevance edit

Increased levels of kininogen in the plasma and tissues are associated with injury, inflammation, myocardial infarction, and diabetes.[3] Additionally, kininogen's role in the contact activation system means that increased levels of kininogen can also contribute to the development of hereditary angioedema,[16] a disorder characterized by periodic episodes of swelling.

KNG is believed to play a role in the formation of thrombi, or blood clots that obstruct a vessel, and in inflammation. The inhibition of KNG is potentially a selective strategy to fight stroke, deep vein thrombosis (DVT),[17] and other venous thromboembolic diseases. Kininogen-1 has also been found to be an effective biomarker in detecting certain types of cancer, namely colorectal cancer.[18]

Bradykinin, the cleavage product of high molecular weight kininogen, is implicated by a class of drugs called angiotensin converting enzyme inhibitors (ACE inhibitors) that aim to increase bradykinin levels by impeding its degradation.[19]

References edit

  1. ^ a b Walter, Robin; Murasko, Donna M.; Sierra, Felipe (1998). "T-Kininogen is a biomarker of senescence in rats". Mechanisms of Ageing and Development. 106 (1–2): 129–144. doi:10.1016/S0047-6374(98)00107-9. PMID 9883978. S2CID 8850085.
  2. ^ Pérez, Viviana; Leiva-Salcedo, Elías; Acuña-Castillo, Claudio; Aravena, Mauricio; Gómez, Christian; Sabaj, Valeria; Colombo, Alicia; Nishimura, Sumiyo; Pérez, Claudio; Walter, Robin (March 2006). "T-kininogen induces endothelial cell proliferation". Mechanisms of Ageing and Development. 127 (3): 282–289. doi:10.1016/j.mad.2005.11.002. hdl:10533/177941. PMID 16378635. S2CID 22878426.
  3. ^ a b Wong, M. K. S. (2016). Handbook of Hormones. Elsevier. doi:10.1016/c2013-0-15395-0. ISBN 978-0-12-801028-0.
  4. ^ Weisel, J. W.; Nagaswami, C.; Woodhead, J. L.; DeLa Cadena, R. A.; Page, J. D.; Colman, R. W. (1994-04-01). "The shape of high molecular weight kininogen. Organization into structural domains, changes with activation, and interactions with prekallikrein, as determined by electron microscopy". The Journal of Biological Chemistry. 269 (13): 10100–10106. doi:10.1016/S0021-9258(17)36995-8. ISSN 0021-9258. PMID 8144509.
  5. ^ Colman, Robert W. (2001-01-06). "Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis". Biological Chemistry. 382 (1): 65–70. doi:10.1515/BC.2001.011. ISSN 1431-6730. PMID 11258675. S2CID 28382339.
  6. ^ Damasceno, Igor Z.; Melo, Katia R. B.; Nascimento, Fabio D.; Souza, Daianne S. P.; Araujo, Mariana S.; Souza, Sinval E. G.; Sampaio, Misako U.; Nader, Helena B.; Tersariol, Ivarne L. S.; Motta, Guacyara (2015-03-30). Sands, Jeff M (ed.). "Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis". PLOS ONE. 10 (3): e0121721. Bibcode:2015PLoSO..1021721D. doi:10.1371/journal.pone.0121721. ISSN 1932-6203. PMC 4379145. PMID 25822177.
  7. ^ Takagaki, Y.; Kitamura, N.; Nakanishi, S. (1985-07-15). "Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens". The Journal of Biological Chemistry. 260 (14): 8601–8609. doi:10.1016/S0021-9258(17)39515-7. ISSN 0021-9258. PMID 2989293.
  8. ^ Furuto-Kato, S.; Matsumoto, A.; Kitamura, N.; Nakanishi, S. (1985-10-05). "Primary structures of the mRNAs encoding the rat precursors for bradykinin and T-kinin. Structural relationship of kininogens with major acute phase protein and alpha 1-cysteine proteinase inhibitor". The Journal of Biological Chemistry. 260 (22): 12054–12059. doi:10.1016/S0021-9258(17)38984-6. ISSN 0021-9258. PMID 2413018.
  9. ^ Veloso, D. (July 1998). "Evidence for the presence of a kininogen-like species in a case of total deficiency of low and high molecular weight kininogens". Brazilian Journal of Medical and Biological Research. 31 (7): 901–910. doi:10.1590/S0100-879X1998000700004. ISSN 0100-879X. PMID 9698753.
  10. ^ Lalmanach, Gilles; Naudin, Clément; Lecaille, Fabien; Fritz, Hans (November 2010). "Kininogens: More than cysteine protease inhibitors and kinin precursors". Biochimie. 92 (11): 1568–1579. doi:10.1016/j.biochi.2010.03.011. PMID 20346387.
  11. ^ Schmaier, A. H. (January 2016). "The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities". Journal of Thrombosis and Haemostasis. 14 (1): 28–39. doi:10.1111/jth.13194. PMID 26565070.
  12. ^ Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas (November 2017). "Factor XII Contact Activation". Seminars in Thrombosis and Hemostasis. 43 (8): 814–826. doi:10.1055/s-0036-1598003. ISSN 0094-6176. PMID 28346966. S2CID 22844127.
  13. ^ Meloni, F. J.; Schmaier, A. H. (1991-04-15). "Low molecular weight kininogen binds to platelets to modulate thrombin-induced platelet activation". The Journal of Biological Chemistry. 266 (11): 6786–6794. doi:10.1016/S0021-9258(20)89569-6. ISSN 0021-9258. PMID 2016293.
  14. ^ Zhang, Xianming; Tan, Fulong; Zhang, Yongkang; Skidgel, Randal A. (2008-03-21). "Carboxypeptidase M and Kinin B1 Receptors Interact to Facilitate Efficient B1 Signaling from B2 Agonists". Journal of Biological Chemistry. 283 (12): 7994–8004. doi:10.1074/jbc.M709837200. ISSN 0021-9258. PMID 18187413.
  15. ^ Hopsu-Havu, V. K.; Mäkinen, K. K.; Glenner, G. G. (1966). "Formation of Bradykinin from Kallidin-10 by Aminopeptidase B". Nature. 212 (5067): 1271–1272. Bibcode:1966Natur.212.1271H. doi:10.1038/2121271a0. PMID 21090475. S2CID 4161553.
  16. ^ Moreno, Adriana; Nunes, Fernanda L.; Januario, Yunan C.; Maia, Luana S.M.; Ferriani, Mariana P.L.; Dias, Marina M.; Aragon, Davi C.; Suffritti, Chiara; Cicardi, Marco; da Silva, Luis L.P.; Arruda, Luisa Karla P. (February 2019). "Cleaved High Molecular Weight Kininogen Correlates With Hereditary Angioedema Due To C1-Inhibitor Deficiency". Journal of Allergy and Clinical Immunology. 143 (2): AB42. doi:10.1016/j.jaci.2018.12.127.
  17. ^ Langhauser, Friederike; Göb, Eva; Kraft, Peter; Geis, Christian; Schmitt, Joachim; Brede, Marc; Göbel, Kerstin; Helluy, Xavier; Pham, Mirko; Bendszus, Martin; Jakob, Peter (2012-11-08). "Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation". Blood. 120 (19): 4082–4092. doi:10.1182/blood-2012-06-440057. ISSN 0006-4971. PMC 3543983. PMID 22936662.
  18. ^ Wang, Jing; Wang, Xinying; Lin, Shiyong; Chen, Chudi; Wang, Congrong; Ma, Qunying; Jiang, Bo (2013-07-23). Kano, Mitsunobu R. (ed.). "Identification of Kininogen-1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer". PLOS ONE. 8 (7): e70519. Bibcode:2013PLoSO...870519W. doi:10.1371/journal.pone.0070519. ISSN 1932-6203. PMC 3720899. PMID 23894665.
  19. ^ Taddei, Stefano; Bortolotto, L. (October 2016). "Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity". American Journal of Cardiovascular Drugs. 16 (5): 309–321. doi:10.1007/s40256-016-0173-4. ISSN 1175-3277. PMID 27260014. S2CID 25709248.

External links edit

January 01, 1970
kininogen, precursor, proteins, kinins, biologically, active, polypeptides, involved, blood, coagulation, vasodilation, smooth, muscle, contraction, inflammatory, regulation, regulation, cardiovascular, renal, systems, contents, types, kininogen, high, molecul. Kininogens are precursor proteins for kinins biologically active polypeptides involved in blood coagulation vasodilation smooth muscle contraction inflammatory regulation and the regulation of the cardiovascular and renal systems Contents 1 Types of kininogen 1 1 High molecular weight kininogen 1 2 Low molecular weight kininogen 1 3 T kininogen 2 Structure 3 Function 3 1 High molecular weight kininogen 3 2 Low molecular weight kininogen 3 3 T kininogen 4 Disease and medical relevance 5 References 6 External linksTypes of kininogen editThere are two main types of kininogen KNG high molecular weight kininogen and low molecular weight kininogen with a third type T kininogen only found in rats but not humans High molecular weight kininogen edit High molecular weight kininogen HK is a non enzymatic cofactor involved in the kinin kallikrein system which plays a role in blood coagulation blood pressure regulation and inflammation It is synthesized in endothelial cells and is produced mostly by the liver It is also a precursor protein for bradykinin nbsp Protein structure of bradykinin Bradykinin is a nine amino acid long polypeptide made by the cleavage of high molecular weight kininogen at D4 It acts as an inflammatory mediator Low molecular weight kininogen edit Low molecular weight kininogen LK is mainly a precursor protein for kallidin LK however is not actively involved in blood coagulation but its byproducts can be later converted and introduced to the coagulation pathway T kininogen edit T kininogen TK is only found in rats and a protein whose function is still being researched TK is believed to be a biological indicator of senescence in rats 1 which can be measured by the level of endothelial cell production during the aging process 2 Structure editHK consists of 644 amino acid residues which are separated into six different domains 3 Domains 1 2 and 3 are called the heavy chain with Domains 2 and 3 having cysteine protease activity 4 Domains 5 and 6 are called the light chain both of which bind specific molecules Domain 5 binds heparin and zinc and selectively binds to anionic surfaces while Domain 6 binds prekallikrein the protease precursor to plasma kallikrein 5 Domain 4 connects the heavy chain and light chain together and its cleavage at this site releases bradykinin 6 LK consists of 427 amino acid residues which can also be separated into a heavy chain and a light chain 7 T kininogen consists of 430 amino acid residues 8 HK and LK are created by the alternative splicing of the same kininogen KNG gene which in humans is located at chromosome 3q27 9 Kininogens are related to cystatins through their similar glycosylated regions 10 Function editHigh molecular weight kininogen edit During the contact activation system CAS also known as the intrinsic pathway the binding of HK factor XII FXII and prekallikrein PK to an anionic surface initiates blood coagulation and the kinin kallikrein system through the activation of a cascade of enzymes 11 Factor XII is a zymogen and upon binding with tissue to the anionic surface exhibits some protease activity starting the enzymatic cascade 12 Both the intrinsic and its corresponding extrinsic pathway which is activated when outside trauma activates tissue factor TF an important glycoprotein culminate in the activation of a serine protease called Factor X Factor X is responsible for the conversion of prothrombin into an important protease in clotting called thrombin which itself participates in the clotting cascade by activating more enzymes and proteins downstream in order to create even more thrombin In the kinin kallikrein system the proteolytic cleavage of HK by the enzyme plasma kallikrein makes bradykinin an inflammatory mediator that can lower blood pressure by way of vasodilation The kinin kallikrein system plays a small role in coagulation nbsp Blood clotting cascade The blood clotting cascade consists of the intrinsic and extrinsic pathway both of which create thrombin a protease involved in blood clotting The intrinsic pathway requires kininogen specifically high molecular weight kininogen as a cofactor HK and LK are noncompetitive inhibitors of activated thrombin 13 Low molecular weight kininogen edit The proteolytical cleavage of LK by tissue kallikreins creates kallidin which is a possible substrate for carboxypeptidase M 14 Kallidin can be converted into bradykinin by Aminopeptidase B 15 creating a connection between LK and the kinin kallikrein system T kininogen edit Research has shown that T kininogen is a possible biomarker for senescence within rats 1 Disease and medical relevance editIncreased levels of kininogen in the plasma and tissues are associated with injury inflammation myocardial infarction and diabetes 3 Additionally kininogen s role in the contact activation system means that increased levels of kininogen can also contribute to the development of hereditary angioedema 16 a disorder characterized by periodic episodes of swelling KNG is believed to play a role in the formation of thrombi or blood clots that obstruct a vessel and in inflammation The inhibition of KNG is potentially a selective strategy to fight stroke deep vein thrombosis DVT 17 and other venous thromboembolic diseases Kininogen 1 has also been found to be an effective biomarker in detecting certain types of cancer namely colorectal cancer 18 Bradykinin the cleavage product of high molecular weight kininogen is implicated by a class of drugs called angiotensin converting enzyme inhibitors ACE inhibitors that aim to increase bradykinin levels by impeding its degradation 19 References edit a b Walter Robin Murasko Donna M Sierra Felipe 1998 T Kininogen is a biomarker of senescence in rats Mechanisms of Ageing and Development 106 1 2 129 144 doi 10 1016 S0047 6374 98 00107 9 PMID 9883978 S2CID 8850085 Perez Viviana Leiva Salcedo Elias Acuna Castillo Claudio Aravena Mauricio Gomez Christian Sabaj Valeria Colombo Alicia Nishimura Sumiyo Perez Claudio Walter Robin March 2006 T kininogen induces endothelial cell proliferation Mechanisms of Ageing and Development 127 3 282 289 doi 10 1016 j mad 2005 11 002 hdl 10533 177941 PMID 16378635 S2CID 22878426 a b Wong M K S 2016 Handbook of Hormones Elsevier doi 10 1016 c2013 0 15395 0 ISBN 978 0 12 801028 0 Weisel J W Nagaswami C Woodhead J L DeLa Cadena R A Page J D Colman R W 1994 04 01 The shape of high molecular weight kininogen Organization into structural domains changes with activation and interactions with prekallikrein as determined by electron microscopy The Journal of Biological Chemistry 269 13 10100 10106 doi 10 1016 S0021 9258 17 36995 8 ISSN 0021 9258 PMID 8144509 Colman Robert W 2001 01 06 Role of the Light Chain of High Molecular Weight Kininogen in Adhesion Cell Associated Proteolysis and Angiogenesis Biological Chemistry 382 1 65 70 doi 10 1515 BC 2001 011 ISSN 1431 6730 PMID 11258675 S2CID 28382339 Damasceno Igor Z Melo Katia R B Nascimento Fabio D Souza Daianne S P Araujo Mariana S Souza Sinval E G Sampaio Misako U Nader Helena B Tersariol Ivarne L S Motta Guacyara 2015 03 30 Sands Jeff M ed Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis PLOS ONE 10 3 e0121721 Bibcode 2015PLoSO 1021721D doi 10 1371 journal pone 0121721 ISSN 1932 6203 PMC 4379145 PMID 25822177 Takagaki Y Kitamura N Nakanishi S 1985 07 15 Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens Primary structures of two human prekininogens The Journal of Biological Chemistry 260 14 8601 8609 doi 10 1016 S0021 9258 17 39515 7 ISSN 0021 9258 PMID 2989293 Furuto Kato S Matsumoto A Kitamura N Nakanishi S 1985 10 05 Primary structures of the mRNAs encoding the rat precursors for bradykinin and T kinin Structural relationship of kininogens with major acute phase protein and alpha 1 cysteine proteinase inhibitor The Journal of Biological Chemistry 260 22 12054 12059 doi 10 1016 S0021 9258 17 38984 6 ISSN 0021 9258 PMID 2413018 Veloso D July 1998 Evidence for the presence of a kininogen like species in a case of total deficiency of low and high molecular weight kininogens Brazilian Journal of Medical and Biological Research 31 7 901 910 doi 10 1590 S0100 879X1998000700004 ISSN 0100 879X PMID 9698753 Lalmanach Gilles Naudin Clement Lecaille Fabien Fritz Hans November 2010 Kininogens More than cysteine protease inhibitors and kinin precursors Biochimie 92 11 1568 1579 doi 10 1016 j biochi 2010 03 011 PMID 20346387 Schmaier A H January 2016 The contact activation and kallikrein kinin systems pathophysiologic and physiologic activities Journal of Thrombosis and Haemostasis 14 1 28 39 doi 10 1111 jth 13194 PMID 26565070 Naudin Clement Burillo Elena Blankenberg Stefan Butler Lynn Renne Thomas November 2017 Factor XII Contact Activation Seminars in Thrombosis and Hemostasis 43 8 814 826 doi 10 1055 s 0036 1598003 ISSN 0094 6176 PMID 28346966 S2CID 22844127 Meloni F J Schmaier A H 1991 04 15 Low molecular weight kininogen binds to platelets to modulate thrombin induced platelet activation The Journal of Biological Chemistry 266 11 6786 6794 doi 10 1016 S0021 9258 20 89569 6 ISSN 0021 9258 PMID 2016293 Zhang Xianming Tan Fulong Zhang Yongkang Skidgel Randal A 2008 03 21 Carboxypeptidase M and Kinin B1 Receptors Interact to Facilitate Efficient B1 Signaling from B2 Agonists Journal of Biological Chemistry 283 12 7994 8004 doi 10 1074 jbc M709837200 ISSN 0021 9258 PMID 18187413 Hopsu Havu V K Makinen K K Glenner G G 1966 Formation of Bradykinin from Kallidin 10 by Aminopeptidase B Nature 212 5067 1271 1272 Bibcode 1966Natur 212 1271H doi 10 1038 2121271a0 PMID 21090475 S2CID 4161553 Moreno Adriana Nunes Fernanda L Januario Yunan C Maia Luana S M Ferriani Mariana P L Dias Marina M Aragon Davi C Suffritti Chiara Cicardi Marco da Silva Luis L P Arruda Luisa Karla P February 2019 Cleaved High Molecular Weight Kininogen Correlates With Hereditary Angioedema Due To C1 Inhibitor Deficiency Journal of Allergy and Clinical Immunology 143 2 AB42 doi 10 1016 j jaci 2018 12 127 Langhauser Friederike Gob Eva Kraft Peter Geis Christian Schmitt Joachim Brede Marc Gobel Kerstin Helluy Xavier Pham Mirko Bendszus Martin Jakob Peter 2012 11 08 Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis blood brain barrier damage and inflammation Blood 120 19 4082 4092 doi 10 1182 blood 2012 06 440057 ISSN 0006 4971 PMC 3543983 PMID 22936662 Wang Jing Wang Xinying Lin Shiyong Chen Chudi Wang Congrong Ma Qunying Jiang Bo 2013 07 23 Kano Mitsunobu R ed Identification of Kininogen 1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer PLOS ONE 8 7 e70519 Bibcode 2013PLoSO 870519W doi 10 1371 journal pone 0070519 ISSN 1932 6203 PMC 3720899 PMID 23894665 Taddei Stefano Bortolotto L October 2016 Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity American Journal of Cardiovascular Drugs 16 5 309 321 doi 10 1007 s40256 016 0173 4 ISSN 1175 3277 PMID 27260014 S2CID 25709248 External links editKininogens at the U S National Library of Medicine Medical Subject Headings MeSH The kinin forming system at sav sk Retrieved from https en wikipedia org w index php title Kininogen amp oldid 1140067837, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.