pISSN 1226-4512 eISSN 2093-3827

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Original Article

Korean J Physiol Pharmacol 2021; 25(5): 413-423

Published online September 1, 2021 https://doi.org/10.4196/kjpp.2021.25.5.413

Copyright © Korean J Physiol Pharmacol.

Curcumin attenuates renal ischemia reperfusion injury via JNK pathway with the involvement of p300/CBP-mediated histone acetylation

Lu Yang1,#, Xiaoxiang Chen1,#, Zirong Bi2, Jun Liao3, Weian Zhao1,*, and Wenqi Huang1,*

Departments of 1Anesthesiology and2Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080,3Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University, Guangzhou 510000, P.R. China

Correspondence to:Wenqi Huang
E-mail: Huangwq@mail.sysu.edu.cn
Weian Zhao
E-mail: zhaoweian5@mail.sysu.edu.cn

#These authors contributed equally to this work.

Received: February 15, 2021; Revised: May 22, 2021; Accepted: June 11, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © Korean J Physiol Pharmacol, pISSN 1226-4512, eISSN 2093-3827

Abstract

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

Keywords: Curcumin, Histone acetylation, MAP kinase signaling system, p300/CBP, Reperfusion Injury for Renal IRI