Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry Disease
The effect of galactose on α-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant withou...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1995-09, Vol.214 (3), p.1219-1224 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Okumiya, T. Ishii, S. Takenaka, T. Kase, R. Kamei, S. Sakuraba, H. Suzuki, Y. |
| description | The effect of galactose on α-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the α-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose. |
| doi_str_mv | 10.1006/bbrc.1995.2416 |
| format | Article |
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Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the α-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.1995.2416</identifier><identifier>PMID: 7575533</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>alpha-Galactosidase - genetics ; alpha-Galactosidase - metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Cercopithecus aethiops ; Codon ; Exons ; Fabry Disease - enzymology ; Fabry Disease - genetics ; Galactose - pharmacology ; Humans ; Kidney ; Kinetics ; Lymphocytes - enzymology ; Point Mutation ; Recombinant Proteins - metabolism ; Transfection</subject><ispartof>Biochemical and biophysical research communications, 1995-09, Vol.214 (3), p.1219-1224</ispartof><rights>1995 Academic Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-75c734bfcc5216f7263da0205a844b42e2b5fab210a79cfeabfb1018f9aeded73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X85724163$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7575533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Okumiya, T.</creatorcontrib><creatorcontrib>Ishii, S.</creatorcontrib><creatorcontrib>Takenaka, T.</creatorcontrib><creatorcontrib>Kase, R.</creatorcontrib><creatorcontrib>Kamei, S.</creatorcontrib><creatorcontrib>Sakuraba, H.</creatorcontrib><creatorcontrib>Suzuki, Y.</creatorcontrib><title>Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry Disease</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The effect of galactose on α-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the α-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose.</description><subject>alpha-Galactosidase - genetics</subject><subject>alpha-Galactosidase - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>Codon</subject><subject>Exons</subject><subject>Fabry Disease - enzymology</subject><subject>Fabry Disease - genetics</subject><subject>Galactose - pharmacology</subject><subject>Humans</subject><subject>Kidney</subject><subject>Kinetics</subject><subject>Lymphocytes - enzymology</subject><subject>Point Mutation</subject><subject>Recombinant Proteins - metabolism</subject><subject>Transfection</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1OwzAQhC0EKuXnyg0pJ24pthPH8REVWpBaIfEnbpbtrCWjNCl2glTeihfhmXDUwo3TSjuzo50PoTOCJwTj4lJrbyZECDahOSn20JhggVNKcL6Pxjg6UirI6yE6CuENY0LyQozQiDPOWJaN0cNc1cp0bYDksVPa1e4TQvKivGv7kCxdCNBEbdl3qulC0trk-yv9vXGVipprkpnSfpNcuwBxcYIOrKoDnO7mMXqe3TxNb9PF_fxuerVITZaJLuXM8CzX1hhGSWE5LbJKYYqZKvNc5xSoZlbp2ERxYSwobTXBpLRCQQUVz47RxTZ37dv3HkInVy4YqGvVQHxecs4KUuIyGidbo_FtCB6sXHu3Un4jCZYDRDlAlANEOUCMB-e75F6voPqz76hFvdzqEOt9OPAyGAeNgcp5MJ2sWvdf9A9tKYJQ</recordid><startdate>19950925</startdate><enddate>19950925</enddate><creator>Okumiya, T.</creator><creator>Ishii, S.</creator><creator>Takenaka, T.</creator><creator>Kase, R.</creator><creator>Kamei, S.</creator><creator>Sakuraba, H.</creator><creator>Suzuki, Y.</creator><general>Elsevier Inc</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></search><sort><creationdate>19950925</creationdate><title>Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry Disease</title><author>Okumiya, T. ; Ishii, S. ; Takenaka, T. ; Kase, R. ; Kamei, S. ; Sakuraba, H. ; Suzuki, Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-75c734bfcc5216f7263da0205a844b42e2b5fab210a79cfeabfb1018f9aeded73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>alpha-Galactosidase - genetics</topic><topic>alpha-Galactosidase - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Cercopithecus aethiops</topic><topic>Codon</topic><topic>Exons</topic><topic>Fabry Disease - enzymology</topic><topic>Fabry Disease - genetics</topic><topic>Galactose - pharmacology</topic><topic>Humans</topic><topic>Kidney</topic><topic>Kinetics</topic><topic>Lymphocytes - enzymology</topic><topic>Point Mutation</topic><topic>Recombinant Proteins - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Okumiya, T.</creatorcontrib><creatorcontrib>Ishii, S.</creatorcontrib><creatorcontrib>Takenaka, T.</creatorcontrib><creatorcontrib>Kase, R.</creatorcontrib><creatorcontrib>Kamei, S.</creatorcontrib><creatorcontrib>Sakuraba, H.</creatorcontrib><creatorcontrib>Suzuki, Y.</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><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Okumiya, T.</au><au>Ishii, S.</au><au>Takenaka, T.</au><au>Kase, R.</au><au>Kamei, S.</au><au>Sakuraba, H.</au><au>Suzuki, Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry Disease</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1995-09-25</date><risdate>1995</risdate><volume>214</volume><issue>3</issue><spage>1219</spage><epage>1224</epage><pages>1219-1224</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The effect of galactose on α-galactosidase missense mutants causing Fabry disease was investigated in the COS-1 cell expression system and lymphoblasts. Three mutant enzymes, A156V, L166V and Q279E, showed increases in activity and amount in COS-1 cells cultured with galactose. Another mutant without catalytic activity, C142Y, did not show any changes. In lymphoblasts cultured with galactose, the enzyme activity increased significantly in four classical Fabry patients with the respective mutations, A156V, L166V, G260A and G373S, and in three atypical Fabry patients with the respective mutations, Q279E, R301Q and M296I. Such an increase was not observed in the other four classical Fabry patients, with C142Y, E66Q/R112C, G328R and N320K, respectively. This suggests that many missense mutations in the α-galactosidase gene causing Fabry disease allow the expression of catalytically active mutant enzymes regardless of the clinical phenotype, which are rapidly degraded under physiological conditions and stabilized by galactose.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>7575533</pmid><doi>10.1006/bbrc.1995.2416</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | alpha-Galactosidase - genetics alpha-Galactosidase - metabolism Amino Acid Sequence Animals Cell Line Cercopithecus aethiops Codon Exons Fabry Disease - enzymology Fabry Disease - genetics Galactose - pharmacology Humans Kidney Kinetics Lymphocytes - enzymology Point Mutation Recombinant Proteins - metabolism Transfection |
| title | Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry Disease |
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