Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface
Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two discontinuous groups: a low-level group below 400 ng/ml and a high-level group above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin. Chim. Acta 229, 123-131]. Molecular genetic studies have shown th...
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| Veröffentlicht in: | Biochemical journal 1996-01, Vol.313 ( Pt 1) (1), p.235-239 |
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| creator | Adachi, T Yamada, H Yamada, Y Morihara, N Yamazaki, N Murakami, T Futenma, A Kato, K Hirano, K |
| description | Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two discontinuous groups: a low-level group below 400 ng/ml and a high-level group above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin. Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in the high-level group have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD [Sandström, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163-19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote subjects was significantly higher than that in heterozygotes and in normal subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased affinity for heparin, as judged by heparin-HPLC, as compared with that from normal donors. This result suggests that the serum EC-SOD in heterozygotes was mainly composed of the mutant form which has reduced heparin affinity. On the other hand, fibroblast cells derived from heterozygote subjects generated mRNA of both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be heterogeneous with regard to the constitution of normal and mutant subunits. The enzyme form consisting of only mutant subunits, the form with the weakest heparin affinity, can be preferentially driven out to the plasma phase, because EC-SOD in the vasculature exists in equilibrium between plasma and the endothelial cell surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50-fold less than that of normal EC-SOD. This result suggests that the binding of m-EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a high level of serum EC-SOD. |
| doi_str_mv | 10.1042/bj3130235 |
| format | Article |
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Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in the high-level group have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD [Sandström, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163-19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote subjects was significantly higher than that in heterozygotes and in normal subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased affinity for heparin, as judged by heparin-HPLC, as compared with that from normal donors. This result suggests that the serum EC-SOD in heterozygotes was mainly composed of the mutant form which has reduced heparin affinity. On the other hand, fibroblast cells derived from heterozygote subjects generated mRNA of both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be heterogeneous with regard to the constitution of normal and mutant subunits. The enzyme form consisting of only mutant subunits, the form with the weakest heparin affinity, can be preferentially driven out to the plasma phase, because EC-SOD in the vasculature exists in equilibrium between plasma and the endothelial cell surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50-fold less than that of normal EC-SOD. This result suggests that the binding of m-EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a high level of serum EC-SOD.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/bj3130235</identifier><identifier>PMID: 8546689</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Arginine - metabolism ; Cattle ; Cell Membrane - metabolism ; Chromatography, High Pressure Liquid ; Culture Media, Conditioned ; DNA, Complementary - genetics ; Endothelium, Vascular - metabolism ; Extracellular Space - enzymology ; Fibroblasts - enzymology ; Fibroblasts - metabolism ; Glycine - metabolism ; Heparin - metabolism ; Heterozygote ; Homozygote ; Humans ; Mutation ; Polymerase Chain Reaction ; RNA, Messenger - analysis ; Superoxide Dismutase - blood ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism</subject><ispartof>Biochemical journal, 1996-01, Vol.313 ( Pt 1) (1), p.235-239</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3515-29494cbf68e71e5050711d3a2af1b611e02035d67ef0c86131c3c0130008316b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216888/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1216888/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8546689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adachi, T</creatorcontrib><creatorcontrib>Yamada, H</creatorcontrib><creatorcontrib>Yamada, Y</creatorcontrib><creatorcontrib>Morihara, N</creatorcontrib><creatorcontrib>Yamazaki, N</creatorcontrib><creatorcontrib>Murakami, T</creatorcontrib><creatorcontrib>Futenma, A</creatorcontrib><creatorcontrib>Kato, K</creatorcontrib><creatorcontrib>Hirano, K</creatorcontrib><title>Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two discontinuous groups: a low-level group below 400 ng/ml and a high-level group above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin. Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in the high-level group have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD [Sandström, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163-19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote subjects was significantly higher than that in heterozygotes and in normal subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased affinity for heparin, as judged by heparin-HPLC, as compared with that from normal donors. This result suggests that the serum EC-SOD in heterozygotes was mainly composed of the mutant form which has reduced heparin affinity. On the other hand, fibroblast cells derived from heterozygote subjects generated mRNA of both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be heterogeneous with regard to the constitution of normal and mutant subunits. The enzyme form consisting of only mutant subunits, the form with the weakest heparin affinity, can be preferentially driven out to the plasma phase, because EC-SOD in the vasculature exists in equilibrium between plasma and the endothelial cell surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50-fold less than that of normal EC-SOD. This result suggests that the binding of m-EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a high level of serum EC-SOD.</description><subject>Animals</subject><subject>Arginine - metabolism</subject><subject>Cattle</subject><subject>Cell Membrane - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Culture Media, Conditioned</subject><subject>DNA, Complementary - genetics</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Extracellular Space - enzymology</subject><subject>Fibroblasts - enzymology</subject><subject>Fibroblasts - metabolism</subject><subject>Glycine - metabolism</subject><subject>Heparin - metabolism</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Superoxide Dismutase - blood</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc9u1DAQxi0EKtvCgQdA8gmJQ2DGThzvBQlVUJAqcQDOkeOMd10ldrBj1H0DHptsu1rBaTSab37z52PsFcI7hFq87-8kShCyecI2WLdQ6Vbop2wDQtWVAoHP2WXOdwBYQw0X7EI3tVJ6u2F_vpc-L34pi4-BR8d348H6QNzFxE3a-bAmlUDJfeB0vyRjaRzLaFKVy0wp3vuB-ODzVBaTiftpNj5lbpxbW5fDA2dPs0lrvwkDpzDEZU-jNyM_onguya3QF-yZM2Oml6d4xX5-_vTj-kt1--3m6_XH28rKBptKbOttbXunNLVIDTTQIg7SCOOwV4gEAmQzqJYcWK1QopUW1ucAaImql1fswyN3Lv1Eg6Ww3jR2c_KTSYcuGt_9Xwl-3-3i7w4FKq31CnhzAqT4q1Beusnn4yUmUCy5a9vtutWD8O2j0KaYcyJ3HoLQHW3rzrat2tf_bnVWnnySfwE47pVq</recordid><startdate>19960101</startdate><enddate>19960101</enddate><creator>Adachi, T</creator><creator>Yamada, H</creator><creator>Yamada, Y</creator><creator>Morihara, N</creator><creator>Yamazaki, N</creator><creator>Murakami, T</creator><creator>Futenma, A</creator><creator>Kato, K</creator><creator>Hirano, K</creator><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>19960101</creationdate><title>Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface</title><author>Adachi, T ; Yamada, H ; Yamada, Y ; Morihara, N ; Yamazaki, N ; Murakami, T ; Futenma, A ; Kato, K ; Hirano, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3515-29494cbf68e71e5050711d3a2af1b611e02035d67ef0c86131c3c0130008316b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Arginine - metabolism</topic><topic>Cattle</topic><topic>Cell Membrane - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Culture Media, Conditioned</topic><topic>DNA, Complementary - genetics</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Extracellular Space - enzymology</topic><topic>Fibroblasts - enzymology</topic><topic>Fibroblasts - metabolism</topic><topic>Glycine - metabolism</topic><topic>Heparin - metabolism</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Superoxide Dismutase - blood</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adachi, T</creatorcontrib><creatorcontrib>Yamada, H</creatorcontrib><creatorcontrib>Yamada, Y</creatorcontrib><creatorcontrib>Morihara, N</creatorcontrib><creatorcontrib>Yamazaki, N</creatorcontrib><creatorcontrib>Murakami, T</creatorcontrib><creatorcontrib>Futenma, A</creatorcontrib><creatorcontrib>Kato, K</creatorcontrib><creatorcontrib>Hirano, K</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>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adachi, T</au><au>Yamada, H</au><au>Yamada, Y</au><au>Morihara, N</au><au>Yamazaki, N</au><au>Murakami, T</au><au>Futenma, A</au><au>Kato, K</au><au>Hirano, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>1996-01-01</date><risdate>1996</risdate><volume>313 ( Pt 1)</volume><issue>1</issue><spage>235</spage><epage>239</epage><pages>235-239</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two discontinuous groups: a low-level group below 400 ng/ml and a high-level group above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin. Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in the high-level group have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD [Sandström, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163-19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote subjects was significantly higher than that in heterozygotes and in normal subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased affinity for heparin, as judged by heparin-HPLC, as compared with that from normal donors. This result suggests that the serum EC-SOD in heterozygotes was mainly composed of the mutant form which has reduced heparin affinity. On the other hand, fibroblast cells derived from heterozygote subjects generated mRNA of both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be heterogeneous with regard to the constitution of normal and mutant subunits. The enzyme form consisting of only mutant subunits, the form with the weakest heparin affinity, can be preferentially driven out to the plasma phase, because EC-SOD in the vasculature exists in equilibrium between plasma and the endothelial cell surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50-fold less than that of normal EC-SOD. This result suggests that the binding of m-EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a high level of serum EC-SOD.</abstract><cop>England</cop><pmid>8546689</pmid><doi>10.1042/bj3130235</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Arginine - metabolism Cattle Cell Membrane - metabolism Chromatography, High Pressure Liquid Culture Media, Conditioned DNA, Complementary - genetics Endothelium, Vascular - metabolism Extracellular Space - enzymology Fibroblasts - enzymology Fibroblasts - metabolism Glycine - metabolism Heparin - metabolism Heterozygote Homozygote Humans Mutation Polymerase Chain Reaction RNA, Messenger - analysis Superoxide Dismutase - blood Superoxide Dismutase - genetics Superoxide Dismutase - metabolism |
| title | Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface |
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