V‑PYRRO/NO downregulates mRNA expression levels of leukotriene C4 synthase during hepatic ischemia reperfusion injury in rats via inhibition of the nuclear factor‑κB activation pathway

Hong,Feng‑Fang; Wang,Yi‑Fan; Liu,Hui; Yang,Mei‑Wen; Yang,Shu‑Long

doi:10.3892/br.2015.533

January-2016 Volume 4 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January-2016 Volume 4 Issue 1

Full Size Image

Article

V‑PYRRO/NO downregulates mRNA expression levels of leukotriene C4 synthase during hepatic ischemia reperfusion injury in rats via inhibition of the nuclear factor‑κB activation pathway

Authors:
- Feng‑Fang Hong
- Yi‑Fan Wang
- Hui Liu
- Mei‑Wen Yang
- Shu‑Long Yang
View Affiliations / Copyright

Affiliations: Department of Physiology, College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Institute of Cancer Research, Jiangxi Academy of Medical Science, Nanchang, Jiangxi 330006, P.R. China, Fuzhou Medical College, Nanchang University, Fuzhou 344000, P.R. China
Pages: 112-116
|
Published online on: October 16, 2015

https://doi.org/10.3892/br.2015.533
Expand metrics +

Abstract

The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O2-vinyl1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 µmol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-κB (NF-κB) p65, p50 and IκBα in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-κB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IκBα protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-κB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V-PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκBα during hepatic I/R injury.

View Figures

View References

1	Montalvo-Jave EE, Piña E, Montalvo-Arenas C, Urrutia R, Benavente-Chenhalls L, Peña-Sanchez J and Geller DA: Role of ischemic preconditioning in liver surgery and hepatic transplantation. J Gastrointest Surg. 13:2074–2083. 2009. View Article : Google Scholar : PubMed/NCBI
2	Yang SL, Huang X, Chen HF, Xu D, Chen LJ, Kong Y and Lou YJ: Increased leukotriene c4 synthesis accompanied enhanced leukotriene c4 synthase expression and activities of ischemia-reperfusion-injured liver in rats. J Surg Res. 140:36–44. 2007. View Article : Google Scholar : PubMed/NCBI
3	Hong F and Yang S: Ischemic preconditioning decreased leukotriene C4 formation by depressing leukotriene C4 synthase expression and activity during hepatic I/R injury in rats. J Surg Res. 178:1015–1021. 2012. View Article : Google Scholar : PubMed/NCBI
4	Qiao YL, Qian JM, Wang FR, Ma ZY and Wang QW: Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells. J Surg Res. 187:653–659. 2014. View Article : Google Scholar : PubMed/NCBI
5	Tsoulfas G and Geller DA: NF-κB in transplantation: Friend or foe? Transpl Infect Dis. 3:212–219. 2001. View Article : Google Scholar : PubMed/NCBI
6	Serio KJ, Johns SC, Luo L, Hodulik CR and Bigby TD: Lipopolysaccharide down-regulates the leukotriene C4 synthase gene in the monocyte-like cell line, THP-1. J Immunol. 170:2121–2128. 2003. View Article : Google Scholar : PubMed/NCBI
7	Demirbilek S, Karaman A, Gürünlüoğlu K, Taş E, Akın M, Aksoy RT, Türkmen E, Edalı MN and Baykarabulut A: Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury. Hepatol Res. 34:84–91. 2006. View Article : Google Scholar : PubMed/NCBI
8	Laroux FS, Pavlick KP, Hines IN, Kawachi S, Harada H, Bharwani S, Hoffman JM and Grisham MB: Role of nitric oxide in inflammation. Acta Physiol Scand. 173:113–118. 2001. View Article : Google Scholar : PubMed/NCBI
9	Harbrecht BG, Kim YM, Wirant EM, Shapiro RA and Billiar TR: PGE2 and LTB4 inhibit cytokine-stimulated nitric oxide synthase type 2 expression in isolated rat hepatocytes. Prostaglandins. 52:103–116. 1996. View Article : Google Scholar : PubMed/NCBI
10	Yang SL and Lou YJ: Sodium nitroprusside decreased leukotriene C4 generation by inhibiting leukotriene C4 synthase expression and activity in hepatic ischemia-reperfusion injured rats. Biochem Pharmacol. 73:724–735. 2007. View Article : Google Scholar : PubMed/NCBI
11	Yang SL, Chen LJ, Kong Y, Xu D and Lou YJ: Sodium nitroprusside regulates mRNA expressions of LTC4 synthesis enzymes in hepatic ischemia/reperfusion injury rats via NF-kappaB signaling pathway. Pharmacology. 80:11–20. 2007. View Article : Google Scholar : PubMed/NCBI
12	Hur GM, Ryu YS, Yun HY, Jeon BH, Kim YM, Seok JH and Lee JH: Hepatic ischemia/reperfusion in rats induces iNOS gene transcription by activation of NF-κB. Biochem Biophys Res Commun. 261:917–922. 1999. View Article : Google Scholar : PubMed/NCBI
13	Inoue T, Kwon AH, Oda M, Kaibori M, Kamiyama Y, Nishizawa M, Ito S and Okumura T: Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes. Hepatology. 32:1037–1044. 2000. View Article : Google Scholar : PubMed/NCBI
14	Isobe M, Katsuramaki T, Hirata K, Kimura H, Nagayama M and Matsuno T: Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver. Transplantation. 68:803–813. 1999. View Article : Google Scholar : PubMed/NCBI
15	Jessup JM, Samara R, Battle P and Laguinge LM: Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway. Clin Exp Metastasis. 21:709–717. 2004. View Article : Google Scholar : PubMed/NCBI
16	Kiemer AK, Vollmar AM, Bilzer M, Gerwig T and Gerbes AL: Atrial natriuretic peptide reduces expression of TNF-α mRNA during reperfusion of the rat liver upon decreased activation of NF-κB and AP-1. J Hepatol. 33:236–246. 2000. View Article : Google Scholar : PubMed/NCBI
17	Luedde T, Assmus U, Wüstefeld T, Meyer zu Vilsendorf A, Roskams T, Schmidt-Supprian M, Rajewsky K, Brenner DA, Manns MP, Pasparakis M, et al: Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. J Clin Invest. 115:849–859. 2005. View Article : Google Scholar : PubMed/NCBI
18	Hong FF, He CS, Tu GL, Guo FX, Chen XB and Yang SL: Nitric oxide donor regulated mRNA expressions of LTC4 synthesis enzymes in hepatic ischemia reperfusion injury rats. Frontier and Future Development of Information Technology in Medicine and Education. (Lecture Notes in Electrical Engineering). Li S, Jin Q, Jiang X and Park JJ: 269:Springer Science Business Media Dordrecht. 3359–3366. 2014. View Article : Google Scholar
19	Saavedra JE, Billiar TR, Williams DL, Kim YM, Watkins SC and Keefer LK: Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver. J Med Chem. 40:1947–1954. 1997. View Article : Google Scholar : PubMed/NCBI
20	Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI
21	Deryckere F and Gannon F: A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. Biotechniques. 16:4051994.PubMed/NCBI
22	Daglar G, Karaca T, Yuksek YN, Gozalan U, Akbiyik F, Sokmensuer C, Gurel B and Kama NA: Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats. J Surg Res. 153:31–38. 2009. View Article : Google Scholar : PubMed/NCBI
23	Takamatsu Y, Shimada K, Chijiiwa K, Kuroki S, Yamaguchi K and Tanaka M: Role of leukotrienes on hepatic ischemia/reperfusion injury in rats. J Surg Res. 119:14–20. 2004. View Article : Google Scholar : PubMed/NCBI
24	Jakobsson PJ, Mancini JA and Ford-Hutchinson AW: Identification and characterization of a novel human microsomal glutathione S-transferase with leukotriene C4 synthase activity and significant sequence identity to 5-lipoxygenase-activating protein and leukotriene C4 synthase. J Biol Chem. 271:22203–22210. 1996. View Article : Google Scholar : PubMed/NCBI
25	Jakobsson PJ, Mancini JA, Riendeau D and Ford-Hutchinson AW: Identification and characterization of a novel microsomal enzyme with glutathione-dependent transferase and peroxidase activities. J Biol Chem. 272:22934–22939. 1997. View Article : Google Scholar : PubMed/NCBI
26	Shimada K, Navarro J, Goeger DE, Mustafa SB, Weigel PH and Weinman SA: Expression and regulation of leukotriene-synthesis enzymes in rat liver cells. Hepatology. 28:1275–1281. 1998. View Article : Google Scholar : PubMed/NCBI
27	Megson LL: Nitric oxide donor drugs. Drugs fulure. 25:701–715. 2000. View Article : Google Scholar
28	Lärfars G, Lantoine F, Devynck MA, Palmblad J and Gyllenhammar H: Activation of nitric oxide release and oxidative metabolism by leukotrienes B4, C4 and D4 in human polymorphonuclear leukocytes. Blood. 93:1399–1405. 1999.PubMed/NCBI
29	Beckh K, Lange AB, Adler G and Weidenbach H: Effects of nitric oxide on leukotriene D4 decreased bile secretion in the perfused rat liver. Life Sci. 61:1947–1952. 1997. View Article : Google Scholar : PubMed/NCBI
30	Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, et al: IKK-1 and IKK-2: Cytokine-activated IkappaB kinases essential for NF-κB activation. Science. 278:860–866. 1997. View Article : Google Scholar : PubMed/NCBI
31	Fan C, Li Q, Ross D and Engelhardt JF: Tyrosine phosphorylation of I kappa B alpha activates NF kappa B through a redox-regulated and c-Src-dependent mechanism following hypoxia/reoxygenation. J Biol Chem. 278:2072–2080. 2003. View Article : Google Scholar : PubMed/NCBI