CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy.

Journal of Molecular and Cellular Cardiology
Anthony J ValenteBysani Chandrasekar

Abstract

Chronic elevation of angiotensin (Ang)-II can lead to myocardial inflammation, hypertrophy and cardiac failure. The adaptor molecule CIKS (connection to IKK and SAPK/JNK) activates the IκB kinase/nuclear factor (NF)-κB and JNK/activator protein (AP)-1 pathways in autoimmune and inflammatory diseases. Since Ang-II is a potent activator of NF-κB and AP-1, we investigated whether CIKS is critical in Ang-II-mediated cardiac hypertrophy. Here we report that Ang-II induced CIKS mRNA and protein expression, CIKS binding to IKK and JNK perhaps functioning as a scaffold protein, CIKS-dependent IKK/NF-κB and JNK/AP-1 activation, p65 and c-Jun phosphorylation and nuclear translocation, NF-κB- and AP-1-dependent IL-18 and MMP-9 induction, and hypertrophy of adult cardiomyocytes isolated from WT, but not CIKS-null mice. These results were recapitulated in WT-cardiomyocytes following CIKS knockdown. Infusion of Ang-II for 7days induced cardiac hypertrophy, increased collagen content, and upregulated CIKS mRNA and protein expression in WT mice, whereas cardiac hypertrophy and collagen deposition were markedly attenuated in the CIKS-null mice, despite a similar increase in systolic blood pressure and DPI-inhibitable superoxide generation in bo...Continue Reading

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Citations

Feb 26, 2013·Heart Failure Reviews·Jamille LocatelliMauro C Isoldi
Aug 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Hye-Lin HaUlrich Siebenlist
Feb 6, 2013·Clinical Science·Jennifer L Wilkinson-BerkaAlex Agrotis
Jun 19, 2013·Clinical Science·Yves Gorin, Karen Block
Jul 23, 2013·Cellular Signalling·Anthony J ValenteBysani Chandrasekar
Mar 5, 2013·Free Radical Biology & Medicine·Anthony J ValenteBysani Chandrasekar
Oct 23, 2012·Cellular Signalling·Balachandar VenkatesanBysani Chandrasekar
Nov 6, 2012·Immunity·Prapaporn PisitkunUlrich Siebenlist
Feb 25, 2014·Free Radical Biology & Medicine·Anthony J ValenteBysani Chandrasekar
Oct 8, 2013·Journal of Molecular and Cellular Cardiology·Jalahalli M SiddeshaBysani Chandrasekar
May 31, 2016·Atherosclerosis·Siva Sankara Vara Prasad SakamuriBysani Chandrasekar
Jun 7, 2018·Physiological Reviews·Steven J ForresterSatoru Eguchi
Nov 23, 2013·Journal of Cellular Physiology·Jalahalli M SiddeshaBysani Chandrasekar
Feb 27, 2020·Circulation Research·Shiju YeGuang Liang
Oct 16, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Grigory RyzhakovIrina A Udalova
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Tao XuJianxun Wang

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