caa a22 4500 606234837 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2513-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2513-0 Angiotensin II down-regulates natriuretic peptide receptor-A expression and guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells: Role of ROS and NF-κB [Elektronische Daten] [Venkatachalam Gopi, Vimala Subramanian, Senthamizharasi Manivasagam, Elangovan Vellaichamy] Atrial natriuretic peptide (ANP)/natriuretic peptide receptor-A (NPR-A) system is suggested as an endogenous anti-hypertrophic protective mechanism of the heart. We have shown previously that Angiotensin II (ANG II), an effector molecule of renin-angiotensin-aldosterone system, down-regulates NPR-A expression and its activity in vivo rat heart. However, the underlying mechanism by which ANG II down-regulates NPR-A expression in the heart is not well understood. Hence, the present investigation was aimed to determine whether ANG II-stimulated reactive oxygen species (ROS) and NF-κB are involved in the down-regulation of NPR-A activity in H9c2 (2-1) cardiac myoblast cells. The H9c2 (2-1) cardiac myoblast cells were exposed to ANG II (10−7M for 20h) with/or without blocker treatment (losartan-10µM, N-acetyl cysteine (NAC)-10mM and pyrrolidine dithiocarbamate (PDTC)-100µM). On exposure, ANG II induced a significant decrease (P<0.001) in the expression of Npr1 (coding for NPR-A) gene and NPR-A receptor-dependent guanylyl cyclase (GC) activity. The level of expression of proto-oncogenes (c-fos, c-myc, and c-jun) and natriuretic peptides (ANP and BNP) was increased in ANG II-treated cells when compared with control cells. Interestingly, ANG II-dependent repression of Npr1 gene expression and guanylyl cyclase (GC) activity was completely restored on treatment with losartan, while only a partial reversal was observed in NAC- and PDTC-co-treated cells. In conclusion, the results of this study suggest that ROS-mediated NF-κB activation mechanism is critically involved in the ANG II-mediated down-regulation of NPR-A expression and its GC activity. Springer Science+Business Media New York, 2015 Angiotensin II nationallicence Guanylyl cyclase-A nationallicence Natriuretic peptide receptor-A nationallicence Nuclear factor-kappa B (NF-κB) nationallicence Reactive oxygen species (ROS) nationallicence Gopi Venkatachalam Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Subramanian Vimala Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Manivasagam Senthamizharasi Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Vellaichamy Elangovan Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 67-79 0300-8177 409:1-2<67 2015 409 11010 https://doi.org/10.1007/s11010-015-2513-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2513-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gopi Venkatachalam Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Subramanian Vimala Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Manivasagam Senthamizharasi Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 700 1- Vellaichamy Elangovan Department of Biochemistry, University of Madras, Guindy Campus, 600 025, Chennai, Tamil Nadu, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 67-79 0300-8177 409:1-2<67 2015 409 11010