Induction of Prothrombin Synthesis by Prothrombin Fragments
The mechanisms by which blood levels of prothrombin (PT) are regulated in the vitamin K-sufficient state are unknown. We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures. Administration to the culture system of exogenous bovine P...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1981-08, Vol.78 (8), p.4772-4776 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Graves, C. Bruce Munns, Theodore W. Carlisle, Thomas L. Grant, Gregory A. Strauss, A. W. |
| description | The mechanisms by which blood levels of prothrombin (PT) are regulated in the vitamin K-sufficient state are unknown. We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures. Administration to the culture system of exogenous bovine PT and rat PT was characterized by increases in endogenous PT synthesis and secretion of 2- and 3-fold, respectively. This induction required endogenous proteolytic degradation of PT. Studies conducted with bovine PT fragment 1 (residues 1--156) demonstrated up to 5-fold increases in PT synthesis. This induction was dose dependent and saturable. Addition of bovine PT chymotryptic fragments to the cells indicated that the NH2-terminal peptide of prothrombin (residues 1--42) contained the requisite structural elements for the induction. Peptide-bound γ -carboxyglutamate residues were required for the observed stimulation of PT synthesis. These results suggest that PT synthesis might be regulated physiologically by the products formed during its normal turnover and consumption during blood coagulation. |
| doi_str_mv | 10.1073/pnas.78.8.4772 |
| format | Article |
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Bruce ; Munns, Theodore W. ; Carlisle, Thomas L. ; Grant, Gregory A. ; Strauss, A. W.</creator><creatorcontrib>Graves, C. Bruce ; Munns, Theodore W. ; Carlisle, Thomas L. ; Grant, Gregory A. ; Strauss, A. W.</creatorcontrib><description>The mechanisms by which blood levels of prothrombin (PT) are regulated in the vitamin K-sufficient state are unknown. We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures. Administration to the culture system of exogenous bovine PT and rat PT was characterized by increases in endogenous PT synthesis and secretion of 2- and 3-fold, respectively. This induction required endogenous proteolytic degradation of PT. Studies conducted with bovine PT fragment 1 (residues 1--156) demonstrated up to 5-fold increases in PT synthesis. This induction was dose dependent and saturable. Addition of bovine PT chymotryptic fragments to the cells indicated that the NH2-terminal peptide of prothrombin (residues 1--42) contained the requisite structural elements for the induction. Peptide-bound γ -carboxyglutamate residues were required for the observed stimulation of PT synthesis. These results suggest that PT synthesis might be regulated physiologically by the products formed during its normal turnover and consumption during blood coagulation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.78.8.4772</identifier><identifier>PMID: 6946425</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Animals ; Benzamidines ; Biochemistry ; Cell lines ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzyme Induction - drug effects ; Gels ; Liver - metabolism ; Liver Neoplasms, Experimental - metabolism ; Peptide Fragments - pharmacology ; Physiological regulation ; Prothrombin - biosynthesis ; Rats ; Secretion ; Structure-Activity Relationship ; Ungulates ; Vitamin K</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1981-08, Vol.78 (8), p.4772-4776</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-7ab640b96be282d02bd11f4c923d8dda734b06a139f68fd6faee260b1c963ad83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/78/8.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/10423$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/10423$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,725,778,782,801,883,27907,27908,53774,53776,58000,58233</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6946425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Graves, C. Bruce</creatorcontrib><creatorcontrib>Munns, Theodore W.</creatorcontrib><creatorcontrib>Carlisle, Thomas L.</creatorcontrib><creatorcontrib>Grant, Gregory A.</creatorcontrib><creatorcontrib>Strauss, A. W.</creatorcontrib><title>Induction of Prothrombin Synthesis by Prothrombin Fragments</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The mechanisms by which blood levels of prothrombin (PT) are regulated in the vitamin K-sufficient state are unknown. We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures. Administration to the culture system of exogenous bovine PT and rat PT was characterized by increases in endogenous PT synthesis and secretion of 2- and 3-fold, respectively. This induction required endogenous proteolytic degradation of PT. Studies conducted with bovine PT fragment 1 (residues 1--156) demonstrated up to 5-fold increases in PT synthesis. This induction was dose dependent and saturable. Addition of bovine PT chymotryptic fragments to the cells indicated that the NH2-terminal peptide of prothrombin (residues 1--42) contained the requisite structural elements for the induction. Peptide-bound γ -carboxyglutamate residues were required for the observed stimulation of PT synthesis. These results suggest that PT synthesis might be regulated physiologically by the products formed during its normal turnover and consumption during blood coagulation.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Benzamidines</subject><subject>Biochemistry</subject><subject>Cell lines</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Induction - drug effects</subject><subject>Gels</subject><subject>Liver - metabolism</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Peptide Fragments - pharmacology</subject><subject>Physiological regulation</subject><subject>Prothrombin - biosynthesis</subject><subject>Rats</subject><subject>Secretion</subject><subject>Structure-Activity Relationship</subject><subject>Ungulates</subject><subject>Vitamin K</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1981</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEURoMotVa3LgShq-5mzKt5IC6k-IKCgroOySRjR2YmNcmI_fe2tkq7cXUX3zn3Xj4AThHMEeTkYt7qmHORi5xyjvdAH0GJMkYl3Ad9CDHPBMX0EBzF-A4hlGMBe6DHJGUUj_vg8qG1XZEq3w59OXwKPs2Cb0zVDp8XbZq5WMWhWewEt0G_Na5N8RgclLqO7mQzB-D19uZlcp9NH-8eJtfTrKBjljKuDaPQSGYcFthCbCxCJS0kJlZYqzmhBjKNiCyZKC0rtXOYQYMKyYi2ggzA1XrvvDONs8XydtC1moeq0WGhvK7UbtJWM_XmPxXBENPx0h9t_OA_OheTaqpYuLrWrfNdVJxwhOQPmK_BIvgYgyv_biCoVm2rVduKCyXUqu2lcL792R--qXcrX3m_6bY_-i9XZVfXyX2lJXi2Bt9j8mHrLYoJ-QbJQZ3l</recordid><startdate>19810801</startdate><enddate>19810801</enddate><creator>Graves, C. Bruce</creator><creator>Munns, Theodore W.</creator><creator>Carlisle, Thomas L.</creator><creator>Grant, Gregory A.</creator><creator>Strauss, A. W.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19810801</creationdate><title>Induction of Prothrombin Synthesis by Prothrombin Fragments</title><author>Graves, C. Bruce ; Munns, Theodore W. ; Carlisle, Thomas L. ; Grant, Gregory A. ; Strauss, A. W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-7ab640b96be282d02bd11f4c923d8dda734b06a139f68fd6faee260b1c963ad83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1981</creationdate><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Benzamidines</topic><topic>Biochemistry</topic><topic>Cell lines</topic><topic>Cells, Cultured</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Induction - drug effects</topic><topic>Gels</topic><topic>Liver - metabolism</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Peptide Fragments - pharmacology</topic><topic>Physiological regulation</topic><topic>Prothrombin - biosynthesis</topic><topic>Rats</topic><topic>Secretion</topic><topic>Structure-Activity Relationship</topic><topic>Ungulates</topic><topic>Vitamin K</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graves, C. Bruce</creatorcontrib><creatorcontrib>Munns, Theodore W.</creatorcontrib><creatorcontrib>Carlisle, Thomas L.</creatorcontrib><creatorcontrib>Grant, Gregory A.</creatorcontrib><creatorcontrib>Strauss, A. W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graves, C. Bruce</au><au>Munns, Theodore W.</au><au>Carlisle, Thomas L.</au><au>Grant, Gregory A.</au><au>Strauss, A. W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of Prothrombin Synthesis by Prothrombin Fragments</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1981-08-01</date><risdate>1981</risdate><volume>78</volume><issue>8</issue><spage>4772</spage><epage>4776</epage><pages>4772-4776</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The mechanisms by which blood levels of prothrombin (PT) are regulated in the vitamin K-sufficient state are unknown. We have studied PT synthesis by Reuber H-35 rat hepatoma cells exposed to vitamin K and [3H]leucine in serum-free cultures. Administration to the culture system of exogenous bovine PT and rat PT was characterized by increases in endogenous PT synthesis and secretion of 2- and 3-fold, respectively. This induction required endogenous proteolytic degradation of PT. Studies conducted with bovine PT fragment 1 (residues 1--156) demonstrated up to 5-fold increases in PT synthesis. This induction was dose dependent and saturable. Addition of bovine PT chymotryptic fragments to the cells indicated that the NH2-terminal peptide of prothrombin (residues 1--42) contained the requisite structural elements for the induction. Peptide-bound γ -carboxyglutamate residues were required for the observed stimulation of PT synthesis. These results suggest that PT synthesis might be regulated physiologically by the products formed during its normal turnover and consumption during blood coagulation.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>6946425</pmid><doi>10.1073/pnas.78.8.4772</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1981-08, Vol.78 (8), p.4772-4776 |
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| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Amino acids Animals Benzamidines Biochemistry Cell lines Cells, Cultured Dose-Response Relationship, Drug Enzyme Induction - drug effects Gels Liver - metabolism Liver Neoplasms, Experimental - metabolism Peptide Fragments - pharmacology Physiological regulation Prothrombin - biosynthesis Rats Secretion Structure-Activity Relationship Ungulates Vitamin K |
| title | Induction of Prothrombin Synthesis by Prothrombin Fragments |
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