Troglitazone-Induced PRODH/POX-Dependent Apoptosis Occurs in the Absence of Estradiol or ERβ in ER-Negative Breast Cancer Cells

The impact of estradiol on troglitazone (TGZ)-induced proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis was studied in wild-type and PRODH/POX-silenced estrogen receptor (ER) dependent MCF-7 cells and ER-independent MDA-MB-231 cells. DNA and collagen biosynthesis were determined by radiometric method, prolidase activity evaluated by colorimetric method, ROS production was measured by fluorescence assay. Protein expression was determined by Western blot and proline concentration by LC/MS analysis. PRODH/POX degrades proline yielding reactive oxygen species (ROS). Estrogens stimulate collagen biosynthesis utilizing free proline and limiting its availability for PRODH/POX-dependent apoptosis. TGZ cytotoxicity was highly pronounced in wild-type MDA-MB-231 cells cultured in medium without estradiol or in the cells cultured in medium with estradiol but deprived of ERβ (by ICI-dependent degradation), while in PRODH/POX-silenced cells the process was not affected. The TGZ cytotoxicity was accompanied by increase in PRODH/POX expression, ROS production, expression of cleaved caspase-3, caspase-9 and PARP, inhibition of collagen biosynthesis, prolidase activity and decrease in intracellular proline concentration. The phenomena were not observed in PRODH/POX-silenced cells. The data suggest that TGZ-induced apoptosis in MDA-MB-231 cells cultured in medium without estradiol or deprived of ERβ is mediated by PRODH/POX and the process is facilitated by proline availability for PRODH/POX by TGZ-dependent inhibition of collagen biosynthesis. It suggests that combined TGZ and antiestrogen treatment could be considered in experimental therapy of estrogen receptor negative breast cancers.

Evaluation of the oxidative stress level and serum prolidase activity in patients with sleep bruxism

Aims and Objective: Sleep bruxism is a complicated disease, and its cause remains controversial.If the aetiology of bruxism is resolved, the treatment can be adjusted to the prevailing aetiological factor.Thus,the aim of this study was to evaluate the oxidative stress level and serum prolidase activity in patients with sleep bruxism. Materials and Methods: Seventy healthy subjects and 51 patients with sleep bruxism were included in this study, and blood samples from all patients were collected. Serum samples were analysed for total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and prolidase activity. Results: The prolidase,TOS and OSI levels were significantly higher in patients with bruxism than in the healthy controls (p = 0.001, p = 0.001, p = 0.001, respectively). The TAS level was significantly lower in bruxism patientsthan in the healthy controls (p = 0.003). Conclusion: The increased TOS, OSI and prolidase levels and decreased TAS levels could be assumed to result in oxidative injury in patients with sleep bruxism. However, the study could not determine whether oxidative imbalance and increased serum prolidase levels could be a cause or a result of bruxism.

The Relationship Between Prolidase Activity and Atrial Electromechanical Changes in Patients with Paroxysmal Atrial Fibrillation

Background:Tissue fibrosis increases in the structure of the atrial tissue of atrial fibrillation patients. Prolidase enzyme regulates collagen synthesis. There may be an association between electrocardiography (ECG) findings and prolidase activity.Objective:This study investigated the association between atrial conduction time and prolidase activity, a collagen synthesis enzyme, and P-wave dispersion (PWD) in patients with Paroxysmal Atrial Fibrillation (PAF).Methods:Exclusion criteria included the age of <18 years, heart failure, diabetes, hypertension, hyperlipidemia, malignancy, cerebrovascular disease, chronic respiratory distress, osteoporosis, rheumatoid arthritis, renal disease, cirrhosis, and other types of arrhythmia. Patients diagnosed with PAF within 48 hours were considered to have a definite diagnosis. PWD was calculated using a 12-lead ECG, and inter- and intraatrial electromechanical delay (EMD) was assessed using tissue Doppler imaging and conventional echocardiography. Serum prolidase levels were measured in both groups.Results:A total of 43 patients with PAF (20 female, 23 male; mean age, 46.8 ± 5.7 years) and 42 healthy volunteers (21 female, 21 male; mean age, 43.9 ± 5.1 years) were included in the study.:Inter- and intraatrial EMD, PWD, minimum P-wave (Pmin), and maximum P-wave (Pmax) measurements were significantly higher (39.7 ± 2.7, 35.7 ± 2.3, p < 0.001; 13.2 ± 2.6, 8.5 ± 1.9, p < 0.001; 47.1 ± 11, 24.1 ± 7.1, p < 0.001; 69.8 ± 8.8, 66.7 ± 10.2, p < 0.130; 114.8 ± 13, 93.6 ± 8.6, p < 0.001, respectively) and serum prolidase levels were significantly lower in patients with PAF compared to healthy controls (3.96 ± 1.2, 8.5 ± 3.56, p < 0.001). In patients with PAF, correlation analysis showed a negative correlation between prolidase levels and intra- and interatrial EMD, PWD, and Pmax (r = -0.41, p < 0.05; r = -0.54, p < 0.05; r = -0.62, p < 0.05; r = -0.49, p < 0.05, respectively). Interatrial EMD showed a significant positive correlation with intraatrial EMD, Pmax, and PWD in patients with PAF (r = 0.90, p < 0.05; r = 0.574, p < 0.05; r = 0.43, p < 0.05, respectively). Additionally, the level of high-sensitivity C-reactive protein (hs-CRP) was significantly higher in patients with PAF (6.6 ± 8, 1.8 ± 1.6, p < 0.001).Conclusion:The decreased plasma prolidase activity in patients with PAF may explain the irregularity of the collagen metabolism of different extracellular components and may indicate the onset of atrial remodeling. Changes in PWD, interatrial EMD, and serum prolidase level may predict PAF before diagnosis.