Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 4, July-August, p. 345–351

Publication type: original article

Language: English

Relationship Between Advanced Oxidation Protein Product Plasma Level and Cathepsin B Activity in Plasma and Polymorphonuclear Cells in Patients with Type 2 Diabetes Mellitus

Związek między stężeniem zaawansowanych produktów oksydacji białek w osoczu a aktywnością katepsyny B w osoczu i granulocytach obojętnochłonnych chorych na cukrzycę typu 2

Agnieszka Piwowar1,, Ewa Żurawska−Płaksej1,, Maria Knapik−Kordecka2,, Maria Warwas1,

1 Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Poland

2 Department and Clinic of Angiology, Hypertension, and Diabetology, Wroclaw Medical University, Poland

Abstract

Background. Hyperglycemia accelerates glycation and oxidative stress (OS) in diabetic patients, resulting in increased levels of advanced glycation end products and advanced oxidation protein products (AOPPs). Changes in the activities of some leukocytic enzymes, for example cathepsin B (CB), derived from polymorphonuclear cells (PMNs) can be observed.
Objectives. The relationship between AOPP plasma level and cathepsin B activity in plasma and PMN extracts in patients with type 2 diabetes mellitus (T2DM) was investigated.
Material and Methods. Fifty−three patients with T2DM and 27 healthy subjects were examined. CB activity in plasma and PMN extracts was measured with a fluorescent substrate (CBZ−Arg−Arg−NMec) and plasma AOPP concentration using a spectrophotometric method with a potassium iodide solution in an acidic environment.
Results. AOPP concentration and CB activity were higher in the diabetic patients than in the control subjects, but significant (p < 0.001) differences between the groups were observed only for plasma AOPP concentration and CB activity in PMN extracts. There was also a medium (r = 0.41) but significant (p < 0.05) correlation between these parameters. In tertiles of AOPP, only plasma CB activities increased progressively, but there were no significant differences between these subgroups. In groups with normal and above−normal values of ESR, plasma AOPP concentration and CB activity in PMN extracts were significantly different (p = 0.0072 and p = 0.0394, respectively).
Conclusion. These results indicate that OS and inflammation affect CB activity, especially in PMN extracts. Identifying the contributions of individual PMN proteases in the context of existing OS is important in the search for biomarkers to monitor diabetic late complications and for therapeutic targets.

Streszczenie

Wprowadzenie. U chorych na cukrzycę hiperglikemia nasila procesy glikacji oraz stres oksydacyjny (OS), co powoduje wzrost stężenia zaawansowanych produktów glikacji białek i zaawansowanych produktów oksydacji białek (AOPP). Prowadzi również do zmian aktywności niektórych enzymów leukocytarnych, np. katepsyny B (CB) pochodzącej z granulocytów obojętnochłonnych (GO).
Cel pracy. Zbadanie, czy istnieje związek między stężeniem AOPP w osoczu a aktywnością CB w osoczu i w ekstraktach GO u chorych na cukrzycę typu 2 (T2DM).
Materiał i metody. Wosoczu i ekstraktach GO pochodzących od 53 pacjentów z T2DM i 27 osób zdrowych oznaczono aktywność CB z użyciem substratu fluorescencyjnego (CBZ−Arg−Arg−NMec). Stężenie AOPP w osoczu mierzono metodą spektrofotometryczną po reakcji z roztworem jodku potasu w środowisku kwaśnym.
Wyniki. Zarówno stężenie AOPP, jak i aktywność CB były wyższe u chorych na cukrzycę niż w grupie kontrolnej, ale różnice istotne statystycznie (p < 0.001) zaobserwowano tylko dla stężenia AOPP w osoczu i aktywności CB w ekstraktach GO. Stwierdzono również przeciętną (r = 0,41), ale istotną statystycznie (p < 0,05), korelację między tymi parametrami. W tertylach wzrastającego stężenia AOPP jedynie aktywność CB w osoczu wzrastała progresywnie, ale nie wykazano zmian o charakterze istotnym statystycznie między podgrupami. W grupach chorych z prawidłową oraz zwiększoną wartością OB stężenie AOPP w osoczu oraz aktywność CB w ekstraktach GO były istotnie różne (odpowiednio p = 0,0072 i p = 0,0394).
Wnioski. Wyniki badań własnych wskazują, że OS i stan zapalny mogą wpływać na aktywność CB, szczególnie w ekstraktach GO. Określenie udziału poszczególnych proteaz granulocytów obojętnochłonnych w kontekście OS jest istotne ze względu na poszukiwanie biomarkerów do monitorowania późnych powikłań cukrzycy i zastosowania odpowiedniej terapii.

Key words

advanced oxidation protein products, cathepsin B, type 2 diabetes mellitus

Słowa kluczowe

zaawansowane produkty oksydacji białek, katepsyna B, cukrzyca typu 2

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