-
Je něco špatně v tomto záznamu ?
Complex metabolic disharmony in PMM2-CDG paves the way to new therapeutic approaches
N. Himmelreich, F. Kikul, L. Zdrazilova, T. Honzik, A. Hecker, G. Poschet, C. Lüchtenborg, B. Brügger, S. Strahl, F. Bürger, JG. Okun, H. Hansikova, C. Thiel
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
- MeSH
- aminokyseliny metabolismus MeSH
- fosfotransferasy (fosfomutasy) * genetika MeSH
- glykosylace MeSH
- lidé MeSH
- lipidy MeSH
- vrozené poruchy glykosylace * genetika terapie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PMM2-CDG is the most common defect among the congenital disorders of glycosylation. In order to investigate the effect of hypoglycosylation on important cellular pathways, we performed extensive biochemical studies on skin fibroblasts of PMM2-CDG patients. Among others, acylcarnitines, amino acids, lysosomal proteins, organic acids and lipids were measured, which all revealed significant abnormalities. There was an increased expression of acylcarnitines and amino acids associated with increased amounts of calnexin, calreticulin and protein-disulfid-isomerase in combination with intensified amounts of ubiquitinylated proteins. Lysosomal enzyme activities were widely decreased as well as citrate and pyruvate levels indicating mitochondrial dysfunction. Main lipid classes such as phosphatidylethanolamine, cholesterol or alkyl-phosphatidylcholine, as well as minor lipid species like hexosylceramide, lysophosphatidylcholines or phosphatidylglycerol, were abnormal. Biotinidase and catalase activities were severely reduced. In this study we discuss the impact of metabolite abnormalities on the phenotype of PMM2-CDG. In addition, based on our data we propose new and easy-to-implement therapeutic approaches for PMM2-CDG patients.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc23016983
- 003
- CZ-PrNML
- 005
- 20231026105344.0
- 007
- ta
- 008
- 231013s2023 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ymgme.2023.107610 $2 doi
- 035 __
- $a (PubMed)37245379
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Himmelreich, Nastassja $u Centre for Child and Adolescent Medicine, Department I, Heidelberg University, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany
- 245 10
- $a Complex metabolic disharmony in PMM2-CDG paves the way to new therapeutic approaches / $c N. Himmelreich, F. Kikul, L. Zdrazilova, T. Honzik, A. Hecker, G. Poschet, C. Lüchtenborg, B. Brügger, S. Strahl, F. Bürger, JG. Okun, H. Hansikova, C. Thiel
- 520 9_
- $a PMM2-CDG is the most common defect among the congenital disorders of glycosylation. In order to investigate the effect of hypoglycosylation on important cellular pathways, we performed extensive biochemical studies on skin fibroblasts of PMM2-CDG patients. Among others, acylcarnitines, amino acids, lysosomal proteins, organic acids and lipids were measured, which all revealed significant abnormalities. There was an increased expression of acylcarnitines and amino acids associated with increased amounts of calnexin, calreticulin and protein-disulfid-isomerase in combination with intensified amounts of ubiquitinylated proteins. Lysosomal enzyme activities were widely decreased as well as citrate and pyruvate levels indicating mitochondrial dysfunction. Main lipid classes such as phosphatidylethanolamine, cholesterol or alkyl-phosphatidylcholine, as well as minor lipid species like hexosylceramide, lysophosphatidylcholines or phosphatidylglycerol, were abnormal. Biotinidase and catalase activities were severely reduced. In this study we discuss the impact of metabolite abnormalities on the phenotype of PMM2-CDG. In addition, based on our data we propose new and easy-to-implement therapeutic approaches for PMM2-CDG patients.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a vrozené poruchy glykosylace $x genetika $x terapie $x metabolismus $7 D018981
- 650 _2
- $a glykosylace $7 D006031
- 650 12
- $a fosfotransferasy (fosfomutasy) $x genetika $7 D017875
- 650 _2
- $a aminokyseliny $x metabolismus $7 D000596
- 650 _2
- $a lipidy $7 D008055
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Kikul, Frauke $u Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
- 700 1_
- $a Zdrazilova, Lucie $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
- 700 1_
- $a Honzik, Tomáš $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
- 700 1_
- $a Hecker, Andreas $u Centre for Child and Adolescent Medicine, Department I, Heidelberg University, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany
- 700 1_
- $a Poschet, Gernot $u Centre for Organismal Studies (COS), Plant Molecular Biology, Heidelberg University, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany
- 700 1_
- $a Lüchtenborg, Christian $u Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
- 700 1_
- $a Brügger, Britta $u Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
- 700 1_
- $a Strahl, Sabine $u Centre for Organismal Studies (COS), Glycobiology, Heidelberg University, Im Neuenheimer Feld 360, 69120 Heidelberg, Germany
- 700 1_
- $a Bürger, Friederike $u Centre for Child and Adolescent Medicine, Department I, Heidelberg University, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany
- 700 1_
- $a Okun, Jürgen G $u Centre for Child and Adolescent Medicine, Department I, Heidelberg University, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany
- 700 1_
- $a Hansikova, Hana $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
- 700 1_
- $a Thiel, Christian $u Centre for Child and Adolescent Medicine, Department I, Heidelberg University, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany. Electronic address: christian.thiel@med.uni-heidelberg.de
- 773 0_
- $w MED00006573 $t Molecular genetics and metabolism $x 1096-7206 $g Roč. 139, č. 3 (2023), s. 107610
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37245379 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20231013 $b ABA008
- 991 __
- $a 20231026105339 $b ABA008
- 999 __
- $a ok $b bmc $g 2000481 $s 1203345
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 139 $c 3 $d 107610 $e 20230516 $i 1096-7206 $m Molecular genetics and metabolism $n Mol Genet Metab $x MED00006573
- LZP __
- $a Pubmed-20231013
