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Urinary ACE Phenotyping as a Research and Diagnostic Tool: Identification of Sex-Dependent ACE Immunoreactivityстатья Электронная публикация
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Kozuch Alexander J., Petukhov Pavel A., Fagyas Miklos, Popova Isolda A., Lindeblad Matthew O., Bobkov Alexander P., Kamalov Armais A., Toth Attila, Dudek Steven M., Danilov Sergei M.
- Журнал: BIOMEDICINES
- Том: 11
- Номер: 3
- Год издания: 2023
- Номер статьи: 953
- DOI: 10.3390/biomedicines11030953
- Аннотация: Background: Angiotensin-converting enzyme (ACE) is highly expressed in renal proximal tubules, but ACE activity/levels in the urine are at least 100-fold lower than in the blood. Decreased proximal tubular ACE has been associated with renal tubular damage in both animal models and clinical studies. Because ACE is shed into urine primarily from proximal tubule epithelial cells, its urinary ACE measurement may be useful as an index of tubular damage. Objective and Methodology: We applied our novel approach—ACE phenotyping—to characterize urinary ACE in volunteer subjects. ACE phenotyping includes (1) determination of ACE activity using two substrates (ZPHL and HHL); (2) calculation of the ratio of hydrolysis of the two substrates (ZPHL/HHL ratio); (3) quantification of ACE immunoreactive protein levels; and (4) fine mapping of local ACE conformation with mAbs to ACE. Principal findings: In normal volunteers, urinary ACE activity was 140-fold less than in corresponding plasma/serum samples and did not differ between males and females. However, urinary ACE immunoreactivity (normalized binding of 25 mAbs to different epitopes) was strongly sex-dependent for the several mAbs tested, an observation likely explained by differences in tissue ACE glycosylation/sialylation between males and females. Urinary ACE phenotyping also allowed the identification of ACE outliers. In addition, daily variability of urinary ACE has potential utility as a feedback marker for dieting individuals pursuing weight loss. Conclusions/Significance: Urinary ACE phenotyping is a promising new approach with potential clinical significance to advance precision medicine screening techniques.
- Добавил в систему: Бобков Александр Петрович