Serum Pon-1 Activity but not Q192R Polymorphism is Related to The Extent of Atherosclerosis

Aim: Paraoxonase-1 (PON1) is an antioxidant enzyme located in high density lipoprotein (HDL). PON1 was defined as a protective factor against atherosclerosis. The aim of this study was to investigate the possible relationship between serum paraoxonase (PONase), homocysteine thiolactonase (HTase) activities and PON1 Q192R polymorphism, and the extent and severity of atherosclerosis. Methods: Blood specimens were collected from 142 individuals who had no coronary artery lesions angiographically (control group) and 128 individuals who had angiographically documented coronary artery disease of several degrees (patient group). The extent and severity of arterial lesions were evaluated by the Gensini scoring system. PONase and HTase activities were measured in serum using a spectrophotometric method. PON1 Q192R polymorphism was evaluated using PCR-RFLP after DNA isolation from blood. Results: Serum PONase and HTase activities were significantly lower in the patient group than in healthy controls (135.7 +/- 56.0 U/mL vs 153.8 +/- 62.0 U/mL, p < 0.05; 36.0 +/- 6.1 U/mL vs 43.0 +/- 4.04 U/mL, p < 0.01; respectively). In the patient group, there was a negative correlation between PONase, HTase activities and the Gensini score (r = -0.168, p = 0.039; r = -0.164, p = 0.006, respectively). In both groups, there was no significant difference in the distribution of PON1 Q192R polymorphism. In the patient group, the distribution of Gensini scores according to genotypes was not significant. Conclusion: It has been concluded that serum PONase and HTase activities might be a more relevant marker than PON1 genotype in evaluating the extent and severity of atherosclerosis.WoSScopu

Unliganded Estrogen Receptor-Alpha Activates Transcription Of The Mammary Gland Na+/I- Symporter Gene

The function of sodium iodide symporter (Na+/I- symporter, or NIS) in mammary epithelial cells is essential for the accumulation of I- in milk; the newborn's first source of I- for thyroid hormone synthesis. Furthermore increased mammary gland NIS expression has previously been shown in human breast cancer. Several hormones and factors including all-trans-retinoic acid (tRA) regulate the expression of NIS. In this study, using breast cancer cell lines, we established that tRA-responsive NIS expression is confined to estrogen receptor-alpha (ER alpha) positive cells and we investigated the role of ER alpha in the regulation of NIS expression. We showed that the suppression of endogenous ER alpha by RNA interference downregulates NIS expression in ER-of. positive mammary cells. Besides, in an ER alpha negative cell line, reintroduction of ER alpha resulted in the expression of NIS in a ligand-independent manner. We also identified a novel estrogen-responsive element in the promoter region of NIS that specifically binds ER alpha and mediates ER alpha-dependent activation of transcription. Our results indicate that unliganded ER alpha (apo-ER alpha) contributes to the regulation of NIS gene expression. (c) 2006 Elsevier Inc. All rights reserved.Wo