• Je něco špatně v tomto záznamu ?

N-acetylgalactosaminide α2,6-sialyltransferase II is a candidate enzyme for sialylation of galactose-deficient IgA1, the key autoantigen in IgA nephropathy

M. Stuchlova Horynova, A. Vrablikova, TJ. Stewart, K. Takahashi, L. Czernekova, K. Yamada, H. Suzuki, BA. Julian, MB. Renfrow, J. Novak, M. Raska,

. 2015 ; 30 (2) : 234-238. [pub] 20141003

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15031814

Grantová podpora
NT11081 MZ0 CEP - Centrální evidence projektů

BACKGROUND: Galactose-deficient O-glycans in the hinge region (HR) of immunoglobulin A1 (IgA1) play a key role in the pathogenesis of IgA nephropathy (IgAN). O-Glycans of circulatory IgA1 consist of N-acetylgalactosamine (GalNAc) with a β1,3-linked galactose; both sugars may be sialylated. In patients with IgAN, α2,6-sialylated GalNAc is a frequent form of the galactose-deficient O-glycans. Prior analyses of IgA1-producing cells had indicated that α2,6-sialyltransferase II (ST6GalNAc-II) is likely responsible for sialylation of GalNAc of galactose-deficient IgA1, but direct evidence is missing. METHODS: We produced a secreted variant of recombinant human ST6GalNAc-II and an IgA1 fragment comprised of Cα1-HR-Cα2. This IgA1 fragment and a synthetic HR peptide with enzymatically attached GalNAc residues served as acceptors. ST6GalNAc-II activity was assessed in vitro and the attachment of sialic acid to these acceptors was detected by lectin blot and mass spectrometry. RESULTS: ST6GalNAc-II was active with both acceptors. High-resolution mass spectrometry analysis revealed that up to three sialic acid residues were added to the GalNAc residues of the HR glycopeptide. CONCLUSIONS: Our data provide direct evidence that ST6GalNAc-II can sialylate GalNAc of galactose-deficient IgA1. As serum levels of galactose-deficient IgA1 with sialylated glycoforms are increased in IgAN patients, our data explain the corresponding part of the biosynthetic pathway.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15031814
003      
CZ-PrNML
005      
20170418095051.0
007      
ta
008      
151005s2015 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/ndt/gfu308 $2 doi
035    __
$a (PubMed)25281698
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Stuchlová Horynová, Milada $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77515, Czech Republic Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. $7 xx0193186
245    10
$a N-acetylgalactosaminide α2,6-sialyltransferase II is a candidate enzyme for sialylation of galactose-deficient IgA1, the key autoantigen in IgA nephropathy / $c M. Stuchlova Horynova, A. Vrablikova, TJ. Stewart, K. Takahashi, L. Czernekova, K. Yamada, H. Suzuki, BA. Julian, MB. Renfrow, J. Novak, M. Raska,
520    9_
$a BACKGROUND: Galactose-deficient O-glycans in the hinge region (HR) of immunoglobulin A1 (IgA1) play a key role in the pathogenesis of IgA nephropathy (IgAN). O-Glycans of circulatory IgA1 consist of N-acetylgalactosamine (GalNAc) with a β1,3-linked galactose; both sugars may be sialylated. In patients with IgAN, α2,6-sialylated GalNAc is a frequent form of the galactose-deficient O-glycans. Prior analyses of IgA1-producing cells had indicated that α2,6-sialyltransferase II (ST6GalNAc-II) is likely responsible for sialylation of GalNAc of galactose-deficient IgA1, but direct evidence is missing. METHODS: We produced a secreted variant of recombinant human ST6GalNAc-II and an IgA1 fragment comprised of Cα1-HR-Cα2. This IgA1 fragment and a synthetic HR peptide with enzymatically attached GalNAc residues served as acceptors. ST6GalNAc-II activity was assessed in vitro and the attachment of sialic acid to these acceptors was detected by lectin blot and mass spectrometry. RESULTS: ST6GalNAc-II was active with both acceptors. High-resolution mass spectrometry analysis revealed that up to three sialic acid residues were added to the GalNAc residues of the HR glycopeptide. CONCLUSIONS: Our data provide direct evidence that ST6GalNAc-II can sialylate GalNAc of galactose-deficient IgA1. As serum levels of galactose-deficient IgA1 with sialylated glycoforms are increased in IgAN patients, our data explain the corresponding part of the biosynthetic pathway.
650    _2
$a autoantigeny $x imunologie $7 D001324
650    _2
$a kultivované buňky $7 D002478
650    _2
$a galaktosa $x nedostatek $7 D005690
650    _2
$a IgA nefropatie $x enzymologie $x imunologie $x patologie $7 D005922
650    _2
$a glykosylace $7 D006031
650    _2
$a lidé $7 D006801
650    _2
$a imunoglobulin A $x metabolismus $7 D007070
650    _2
$a hmotnostní spektrometrie $7 D013058
650    _2
$a kyselina N-acetylneuraminová $x metabolismus $7 D019158
650    _2
$a rekombinantní proteiny $x imunologie $x metabolismus $7 D011994
650    _2
$a sialyltransferasy $x metabolismus $7 D012799
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Vrablikova, Alena $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77515, Czech Republic Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
700    1_
$a Stewart, Tyler J $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
700    1_
$a Takahashi, Kazuo $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
700    1_
$a Czernekova, Lydie $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77515, Czech Republic Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
700    1_
$a Yamada, Koshi $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
700    1_
$a Suzuki, Hitoshi $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.
700    1_
$a Julian, Bruce A $u Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
700    1_
$a Renfrow, Matthew B $u Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
700    1_
$a Novák, Jan $u Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. $7 _AN065782
700    1_
$a Raška, Milan, $u Department of Immunology, Faculty of Medicine and Dentistry, Palacky University, Olomouc 77515, Czech Republic Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. $d 1967- $7 xx0060585
773    0_
$w MED00010288 $t Nephrology, dialysis, transplantation official publication of the European Dialysis and Transplant Association - European Renal Association $x 1460-2385 $g Roč. 30, č. 2 (2015), s. 234-238
856    41
$u https://pubmed.ncbi.nlm.nih.gov/25281698 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20151005 $b ABA008
991    __
$a 20170418095359 $b ABA008
999    __
$a ok $b bmc $g 1092690 $s 914940
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 30 $c 2 $d 234-238 $e 20141003 $i 1460-2385 $m Nephrology, dialysis, transplantation $n Nephrol Dial Transplant $x MED00010288
GRA    __
$a NT11081 $p MZ0
LZP    __
$a Pubmed-20151005

Najít záznam

Citační ukazatele

Možnosti archivace