Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Wang,Wei; Meng,Xin; Wang,Jing; Li,Yong

doi:10.3892/etm.2018.6423

Improved heart failure by Rhein lysinate is associated with p38MAPK pathway

Authors:
- Wei Wang
- Xin Meng
- Jing Wang
- Yong Li
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Affiliations: Internal Medicine-Cardiovascular Department, Tengzhou Central People's Hospital Affiliated to Jining Medical University, Zaozhuang, Shandong 277500, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/etm.2018.6423
Pages: 2046-2051

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Abstract

The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal rat ventricular myocytes (NRVMs) and congestive heart failure induced by co‑arctation of the abdominal aorta. Male Sprague‑Dawley rats were divided into 3 groups randomly: co‑arctation of abdominal aorta group (A group, n=10), sham operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To establish an in vitro oxidative stressed cardiomyocyte model, NRVMs were treated with 10 µM H2O2 for 24 h. MTT assay indicated that H2O2 treatment reduced primary cardiomyocyte viability in a time‑ and dose‑ dependent manner, whereas RHL abolished the detrimental effects of H2O2, indicating a protective role of RHL. Further study demonstrated that H2O2‑induced reactive oxygen species (ROS) production was reversed by RHL. Then, TUNEL staining was carried out and the results revealed that H2O2 markedly enhanced primary cardiomyocyte apoptosis. Conversely, RHL incubation decreased H2O2‑induced cell apoptosis, indicating the protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38 activation was identified in the failed heart. Notably, treatment with RHL reduced p38 activation. In addition, RHL significantly enhanced the expression of anti‑apoptotic protein, B cell lymphoma (Bcl)‑2, however markedly reduced the protein level of Bcl‑2 associated X, apoptosis regulator in primary cardiomyocytes, indicating its anti‑apoptotic role in the cardiac setting. Overall, RHL protects heart failure primarily by reducing ROS production and cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase activation.

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1	Suzuki H, Nodera M, Kamioka M, Kaneshiro T, Kamiyama Y and Takeishi Y: Intracardiac impedance after cardiac resynchronization therapy is a novel predictor for worsening of heart failure. Heart Vessels. 32:926–931. 2017. View Article : Google Scholar : PubMed/NCBI
2	Senni M, D'Elia E, Emdin M and Vergaro G: Biomarkers of heart failure with preserved and reduced ejection fraction. Handb Exp Pharmacol. 243:79–108. 2017. View Article : Google Scholar : PubMed/NCBI
3	Pecoraro A, Crescenzi L, Carucci L, Genovese A and Spadaro G: Heart failure not responsive to standard immunosuppressive therapy is successfully treated with high dose intravenous immunoglobulin therapy in a patient with eosinophilic granulomatosis with polyangiitis (EGPA). Int Immunopharmacol. 45:13–15. 2017. View Article : Google Scholar : PubMed/NCBI
4	Marx N: Heart failure and diabetes-underestimated, underdiagnosed and poorly understood: A call for action. Diab Vasc Dis Res. 14:67–68. 2017. View Article : Google Scholar : PubMed/NCBI
5	Mathur A, Fernández-Avilés F, Dimmeler S, Hauskeller C, Janssens S, Menasche P, Wojakowski W, Martin JF and Zeiher A: BAMI Investigators: The consensus of the Task Force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for the treatment of acute myocardial infarction and heart failure: Update 2016. Eur Heart J. Feb 15–2017.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
6	Arabacilar P and Marber M: The case for inhibiting p38 mitogen-activated protein kinase in heart failure. Front Pharmacol. 6:1022015. View Article : Google Scholar : PubMed/NCBI
7	Cook SA, Sugden PH and Clerk A: Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease. J Mol Cell Cardiol. 31:1429–1434. 1999. View Article : Google Scholar : PubMed/NCBI
8	Di Lisa F, Kaludercic N and Paolocci N: β₂-Adrenoceptors, NADPH oxidase, ROS and p38 MAPK: Another ‘radical’ road to heart failure? Br J Pharmacol. 162:1009–1011. 2011. View Article : Google Scholar : PubMed/NCBI
9	Marber MS, Rose B and Wang Y: The p38 mitogen-activated protein kinase pathway-a potential target for intervention in infarction, hypertrophy, and heart failure. J Mol Cell Cardiol. 51:485–490. 2011. View Article : Google Scholar : PubMed/NCBI
10	Wei J, Zhen YZ, Cui J, He FL, Shen T, Hu G, Ren XH and Lin YJ: Rhein lysinate decreases inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease. Arch Pharm Res. 39:960–969. 2016. View Article : Google Scholar : PubMed/NCBI
11	Lin YJ, Zhen YZ, Wei J, Liu B, Yu ZY and Hu G: Effects of Rhein lysinate on H2O2-induced cellular senescence of human umbilical vascular endothelial cells. Acta Pharmacol Sin. 32:1246–1252. 2011. View Article : Google Scholar : PubMed/NCBI
12	Lin YJ, Zhen YZ, Zhao YF, Wei J and Hu G: Rhein lysinate induced S-phase arrest and increased the anti-tumor activity of 5-FU in HeLa cells. Am J Chin Med. 39:817–825. 2011. View Article : Google Scholar : PubMed/NCBI
13	Hannan RD, Luyken J and Rothblum LI: Regulation of ribosomal DNA transcription during contraction-induced hypertrophy of neonatal cardiomyocytes. J Biol Chem. 271:3213–3220. 1996. View Article : Google Scholar : PubMed/NCBI
14	Song B, Li T, Chen S, Yang D, Luo L, Wang T, Han X, Bai L and Ma A: Correlations between MTP and ros levels of peripheral blood lymphocytes and readmission in patients with chronic heart failure. Heart Lung Circ. 25:296–302. 2016. View Article : Google Scholar : PubMed/NCBI
15	Rojas A, Mercadal E, Figueroa H and Morales MA: Advanced Glycation and ROS: A link between diabetes and heart failure. Curr Vasc Pharmacol. 6:44–51. 2008. View Article : Google Scholar : PubMed/NCBI
16	Astashkin EI, Glezer MG, Vinokurov MG, Egorova ND, Orekhova NS, Novikova AN, Grachev SV, Yurinskaya MM and Sobolev KE: Actovegin reduces the ROS level in blood samples of heart failure patients and diminishes necrosis of SK-N-SH human neuroblastoma cells. Dokl Biol Sci. 448:57–60. 2013. View Article : Google Scholar : PubMed/NCBI
17	Borchi E, Bargelli V, Stillitano F, Giordano C, Sebastiani M, Nassi PA, d'Amati G, Cerbai E and Nediani C: Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochim Biophys Acta. 1802:331–338. 2010. View Article : Google Scholar : PubMed/NCBI
18	Liu J, Zhang K, Zhen YZ, Wei J, Hu G, Gao JL, Tian YX and Lin YJ: Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo. Oncol Rep. 35:1711–1717. 2016. View Article : Google Scholar : PubMed/NCBI
19	Lin YJ, Hu G, Li KJ, Zhao YF, Wei J and Zhen YZ: The protection of Rhein lysinate to liver in diabetic mice induced by high-fat diet and streptozotocin. Arch Pharm Res. 38:885–892. 2015. View Article : Google Scholar : PubMed/NCBI
20	Hafstad AD, Nabeebaccus AA and Shah AM: Novel aspects of ROS signalling in heart failure. Basic Res Cardiol. 108:3592013. View Article : Google Scholar : PubMed/NCBI
21	Zuo L, Chuang CC, Hemmelgarn BT and Best TM: Heart failure with preserved ejection fraction: Defining the function of ROS and NO. J Appl Physiol (1985). 119:944–951. 2015. View Article : Google Scholar : PubMed/NCBI
22	Heusch P, Canton M, Aker S, van de Sand A, Konietzka I, Rassaf T, Menazza S, Brodde OE, Di Lisa F, Heusch G and Schulz R: The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits. Br J Pharmacol. 160:1408–1416. 2010. View Article : Google Scholar : PubMed/NCBI
23	Hoefer J, Azam MA, Kroetsch JT, Leong-Poi H, Momen MA, Voigtlaender-Bolz J, Scherer EQ, Meissner A, Bolz SS and Husain M: Sphingosine-1-phosphate-dependent activation of p38 MAPK maintains elevated peripheral resistance in heart failure through increased myogenic vasoconstriction. Circ Res. 107:923–933. 2010. View Article : Google Scholar : PubMed/NCBI
24	Kerkela R and Force T: p38 mitogen-activated protein kinase: A future target for heart failure therapy? J Am Coll Cardiol. 48:556–558. 2006. View Article : Google Scholar : PubMed/NCBI
25	Kita T, Ogawa M, Sato H, Kasai K, Tanaka T and Tanaka N: Role of p38 mitogen-activated protein kinase pathway on heart failure in the infant rat after burn injury. Int J Exp Pathol. 89:55–63. 2008. View Article : Google Scholar : PubMed/NCBI
26	Nemoto S, Sheng Z and Lin A: Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte hypertrophy. Mol Cell Biol. 18:3518–3526. 1998. View Article : Google Scholar : PubMed/NCBI
27	Irukayama-Tomobe Y, Miyauchi T, Kasuya Y, Sakai S, Goto K and Yamaguchi I: Activation of peroxisome proliferator-activated receptor-alpha decreases endothelin-1-induced p38 mitogen-activated protein kinase activation in cardiomyocytes. J Cardiovasc Pharmacol. 44 Suppl 1:S358–S361. 2004. View Article : Google Scholar : PubMed/NCBI
28	Inagaki K, Satoh T, Yagi-Utsumi M, Le Gulluche AC, Anzai T, Uekusa Y, Kamiya Y and Kato K: Redox-coupled structural changes of the catalytic a' domain of protein disulfide isomerase. FEBS Lett. 589:2690–2694. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhang D, Gaussin V, Taffet GE, Belaguli NS, Yamada M, Schwartz RJ, Michael LH, Overbeek PA and Schneider MD: TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice. Nat Med. 6:556–563. 2000. View Article : Google Scholar : PubMed/NCBI