PP.13.21: MECHANISM OF ACROLEIN-INDUCED VASCULAR TOXICITY. (June 2015)

• Record Type: Journal Article
• Authors: Yousefipour, Z.; Newaz, M.A.
• Is Part Of: Journal of hypertension. Volume 33(2015)Supplement 1
• Publication Date: 2015-06
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000468093.92407.cb
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Modulation of inflammatory signaling has been elucidated in different disease models including vascular biology. Acrolein is an environmental pollutant and a product of lipid peroxidation. Acrolein-induced toxicity in vasculature has been linked to activation of inflammatory pathways. Serum response factor (SRF), a transcription factor, has been shown to regulate cell development, differentiation and proliferation. SRF-induced proliferation involves molecule such as Early growth response-1 (Egr-1). Egr-1, a nuclear protein, functions as a transcriptional regulator and activates the transcription of several hundred genes. Heme oxygenase-1 (HO-1) is important in resistance to oxidative stress. This study explored regulatory influence of SRF on Egr-1 and HO-1-dependent signaling in acrolein-mediated inflammatory responses. Design and method: Male sprague-dawley rats (8 weeks old) were exposed to 2 mg/kg/day of acrolein (gavage, 1 week) alone or in combination with rosiglitazone [ROZ, peroxisome proliferator-activated receptor gamma (PPAR gamma agonist, 10 mg/kg/day, gavages, 1 week] or clofibrate [CLO, peroxisome proliferator-activated receptor alpha (PPAR alpha agonist, 250 mg/kg/day, i.p. 1 week]. At the end of the treatment period isoprostane level was measured in urine. Changes in the expression of SRF, Egr-1, and HO-1 proteins in kidney homogenate were determined by western blot. Results: Our results indicated increased generation of ROS in rats treated with acrolein with a reduction after treatment with ROZ and CLO. Acrolein increased SRF and decreased Egr-1 and HO-1 protein expression (∼2-fold, 1.5 fold and 1.8 fold respectively). SRF expression was attenuated in the presence of CLO/ROZ (52% and 45% respectively; p < 0.05). Acrolein treatment significantly reduced TAS expression and only ROZ treatment improved TAS expression. ROZ reduced SRF band increased Erg-1 and HO-1 expression. Conclusions: We concluded that PPAR gamma agonist can improve acrolein toxicity through up-regulation of HO-1 and Egr-1 expression which seems to be SRF dependent.