Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of aortic media from L-NAME and atorvastatin treated male rats

ABSTRACT: One-month-old male Fischer 344 rats with an initial body weight of 150 g were used for this study and were divided into 7 groups: a control group (30 days), 2 groups intoxicated with L-NAME (50 mg/kg per day in the drinking water; Sigma Chemical Co) for 15 and 30 days, 2 groups treated with atorvastatin (100 mg/kg per day in the drinking water; Pfizer France) for 15 and 30 days and 2 groups receiving L-NAME (50 mg/kg/day) and atorvastatin (100 mg/kg/day) for 15 and 30 days (6 rats in each group). We compared transcriptional profile of aortic medias of control and treated rats using the Affymetrix U34 set. For each a set (chips A, B and C), we pooled RNAs from two rats. The same labelled extract was used for chips A, B and then C. We used 3 independant pools of RNA from 2 rats per treatment group to obtain biological triplicates.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Frederique Capron

PROVIDER: E-MEXP-33 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Androgens are required for prostate development, growth and physiology, by activating the androgen receptor (AR) upon activation by testosterone and dihydrotestosterone (DHT), the AR undergoes conformational changes, dimerizes and translocates to the cell nucleus regulation important genes releted to cell survival. Understanding the mechanisms of androgen regulation in the prostate gland is important, because the prostate is affected by several different diseases, in particular prostate cancer (PCa). Several ways exist to treat prostate cancer and promote epithelial cell death. Treatments involving androgen manipulation include surgical castration (bilateral orchiectomy), antiandrogens (usually AR antagonists), or substances that inhibit androgen synthesis (5 alpha-reductase inhibitors, gonadotrophin-releasing hormone blockers). 17 beta-estradiol exerts anti-androgen effects by blocking the hypothalamic production of gonadotropin-releasing hormone and thereby inhibiting the production of testosterone by the testes , but also acts locally via interactions with either of the estrogen receptors found in the gland. It is known that the kinetics of apoptosis are different in the rat ventral prostate (VP) of castrated rats (Cas group) and in rats subjected to 17 beta-estradiol high dose (group E2) or their combination (group Cas+E2), with an evident additive effect in the latter situation (Garcia-Florez et al, 2005). The microarray approach was done to figure out what genes are expressed and how the cells of ventral prostate gland responses when the androgen is not available comparing three diferent androgen deprivation methods (sirurgical castration, high dose of 17-beta estradiol and both treatment combined). Forty-eight 21-day-old male Wistar rats were obtained from the Multidisciplinary Center for Biological Research (CEMIB), University of Campinas. The animals were kept under normal light conditions (12-h light:dark cycle) and received filtered tap water and Purina rodent chow ad libitum. On the 90th day after birth, the rats were divided in four groups (n=3) and assigned to different treatment groups. To cause androgen deprivation, we utilized three different procedures with different effects on epithelial cell apoptosis. Animals in the first group were castrated (Cas) by orchiectomy via scrotal incision under ketamine (150 mg/Kg body weight) and xylazin (10 mg/kg body weight) anesthesia. Animals in the second group received a 25 mg/Kg body weight dose of 17β-estradiol diluted in corn oil (E2 group). The third group received a combination of both treatments (Cas+E2 group) (combined orchiectomy and 17β-estradiol). In the control group (Ct; normal androgen and estrogen), the animals received only the vehicle. Three days after the treatments, the rats were killed by anesthetic overdose, and the ventral prostate was dissected out for the microarray and immunohistochemistry analyses.

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Transcription profiling of aortic media from L-NAME and atorvastatin treated male rats

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