التفاصيل البيبلوغرافية
| العنوان: |
Increased plasma protein homocysteinylation in hemodialysis patients |
| المؤلفون: |
Filomena Acanfora, Alessandra F. Perna, Cinzia Lombardi, N. G. De Santo, Ersilia Satta, Diego Ingrosso |
| المساهمون: |
Perna, Alessandra, Satta, E., Acanfora, F., Lombardi, C., Ingrosso, Diego, DE SANTO, N. G. |
| بيانات النشر: |
NATURE PUBLISHING GROUP, 2006. |
| سنة النشر: |
2006 |
| مصطلحات موضوعية: |
Adult, Male, Models, Molecular, Hyperhomocysteinemia, medicine.medical_specialty, Folate, Homocysteine, medicine.medical_treatment, In Vitro Techniques, Xenobiotics, chemistry.chemical_compound, Folic Acid, Renal Dialysis, Internal medicine, medicine, Humans, Serum Albumin, Aged, Uremia, hemodialysis, Chemistry, Albumin, Blood Proteins, Middle Aged, medicine.disease, folates, Blood proteins, Vitamin B 6, Vitamin B 12, Endocrinology, Biochemistry, Protein homocysteinylation, Nephrology, Cardiovascular Diseases, Case-Control Studies, Toxicity, Female, Hemodialysis, Hemodialysi, Protein Processing, Post-Translational, Cysteine, Protein Binding |
| الوصف: |
Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-Nhomocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent *S*S* bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n¼28) compared to controls (n¼14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by highpressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-Nhomocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albuminbinding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment. Hyperhomocysteinemia, an independent cardiovascular risk factor, is present in the majority of hemodialysis patients. Among the postulated mechanisms of toxicity, protein homocysteinylation is potentially able to cause significant alterations in protein function. Protein homocysteinylation occurs through various mechanisms, among which is the post-translational acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine (Hcy) thiolactone). Another type of protein homocysteinylation occurs through the formation of a covalent -S-S- bond, found primarily with cysteine residues (protein-S-homocysteinylation). Scant data are available in the literature regarding the extent to which alterations in protein homocysteinylation are present in uremic patients on hemodialysis, and the effects of folate treatment are not known. Protein homocysteinylation was measured in a group of hemodialysis patients (n = 28) compared to controls (n = 14), with a new method combining protein reduction, gel filtration and Hcy derivatization. Chemical hydrolysis was performed, followed by high-pressure liquid chromatography separation. The effects of folate treatment on protein homocysteinylation, as well as in vitro binding characteristics were evaluated. Plasma Hcy, protein-N-homocysteinylation and protein-S-homocysteinylation were significantly higher in patients vs controls. Plasma Hcy and protein-S-homocysteinylation were significantly correlated. After 2 months of oral folate treatment, protein-N-homocysteinylation was normalized, and protein-S-homocysteinylation was significantly reduced. Studies on albumin-binding capacity after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam-binding site. In conclusion, increased protein homocysteinylation is present in hemodialysis patients, with possible consequences in terms of protein function. This alteration can be partially reversed after folate treatment. © 2006 International Society of Nephrology. |
| اللغة: |
English |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::825bee1aea2645f9b1b60a077ef8b6fcTest
http://hdl.handle.net/11591/214927Test |
| حقوق: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....825bee1aea2645f9b1b60a077ef8b6fc |
| قاعدة البيانات: |
OpenAIRE |
