Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2011 | Research

Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells

Authors: Ruey-Horng Shih, Shin-Ei Cheng, Li-Der Hsiao, Yu Ru Kou, Chuen-Mao Yang

Published in: Journal of Neuroinflammation | Issue 1/2011

Abstract

Background

In the brain, the inducible form of heme oxygenase (HO-1) has been recently demonstrated to exacerbate early brain injury produced by intracerebral hemorrhagic stroke which incident rate has been correlated with cigarette smoking previously. Interestingly, cigarette smoke (CS) or chemicals present in CS have been shown to induce HO-1 expression in various cell types, including cerebral endothelial cells. However, the mechanisms underlying CS modulating HO-1 protein expression are not completely understood in the brain vessels.

Objective

The aim of the present study was to investigate the mechanisms underlying CS modulating HO-1 protein expression in cerebral endothelial cells.

Methods

Cultured cerebral endothelial cells (bEnd.3) were used to investigate whether a particulate phase of cigarette smoke extract (PPCSE) regulates HO-1 expression and to investigate the molecular mechanisms involved in HO-1 expression in bEnd.3 cells.

Results

We demonstrated that PPCSE (30 μg/ml) significantly induced HO-1 protein expression and its enzymatic activity in bEnd.3 cells determined by western blotting and bilirubin formation, respectively. PPCSE-induced HO-1 expression was mediated through phosphatidylcholine phospholipase C (PC-PLC), PKCδ, and PI3K/Akt which were observed by pretreatment with their respective pharmacological inhibitors or transfection with dominant negative mutants of PKCδ and Akt. ROS scavenger (N-acetyl-L-cysteine, NAC) blocked the PPCSE-induced ROS generation and HO-1 expression. Pretreatment with selective inhibitors of PKCδ (rottlerin) and NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin (APO)] attenuated the PPCSE-induced NADPH oxidase activity, ROS generation, and HO-1 expression. In addition, we found that PPCSE induced PI3K/Akt activation via NADPH oxidase/ROS-dependent PDGFR phosphorylation.

Conclusions

Taken together, these results suggested that PPCSE-induced HO-1 expression is mediated by a PC-PLC/PKCδ/NADPH oxidase-dependent PDGFR/PI3K/Akt pathway in bEnd.3 cells.

Available only for authorised users

van der Toorn M, Rezayat D, Kauffman HF, Bakker SJ, Gans RO, Koeter GH, Choi AM, van Oosterhout AJ, Slebos DJ: Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2009, 297: L109-L114. 10.1152/ajplung.90461.2008.PubMedCentralCrossRefPubMed

Meyers DG, Neuberger JS, He J: Cardiovascular effect of bans on smoking in public places: a systematic review and meta-analysis. J Am Coll Cardiol. 2009, 54: 1249-1255. 10.1016/j.jacc.2009.07.022.CrossRefPubMed

Peto R, Lopez AD, Boreham J, Thun M, Heath C: Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet. 1992, 339: 1268-1278. 10.1016/0140-6736(92)91600-D.CrossRefPubMed

Mostaza JM, Martín-Jadraque R, Vicente I, San Martin MA, Lahoz C: Patients at high risk of cerebrovascular disease: the REACH study. Cerebrovasc Dis. 2009, 27 (Suppl 1): 77-81.CrossRefPubMed

Ryter SW, Alam J, Choi AM: Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006, 86: 583-650. 10.1152/physrev.00011.2005.CrossRefPubMed

Wang J, Doré S: Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage. Brain. 2007, 130: 1643-1652. 10.1093/brain/awm095.PubMedCentralCrossRefPubMed

Knorr-Wittmann C, Hengstermann A, Gebel S, Alam J, Muller T: Characterization of Nrf2 activation and heme oxygenase-1 expression in NIH3T3 cells exposed to aqueous extracts of cigarette smoke. Free Rad Biol Med. 2005, 39: 1438-1448. 10.1016/j.freeradbiomed.2005.07.003.CrossRefPubMed

Palozza P, Serini S, Currò D, Calviello G, Igarashi K, Mancuso C: beta-Carotene and cigarette smoke condensate regulate heme oxygenase-1 and its repressor factor Bach1: relationship with cell growth. Antioxid Redox Signal. 2006, 8: 1069-1080. 10.1089/ars.2006.8.1069.CrossRefPubMed

Tagawa A, Kaneko T, Shinohara T, Ueda A, Sato T, Ishigatsubo Y: Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal mucosal permeability in guinea pigs in vivo. Inflamm Res. 2005, 54: 229-234. 10.1007/s00011-005-1348-7.CrossRefPubMed

10.

Wu CC, Hsieh CW, Lai PH, Lin JB, Liu YC, Wung BS: Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein. Toxicol Appl Pharmacol. 2006, 214: 244-252. 10.1016/j.taap.2005.12.013.CrossRefPubMed

11.

Shih RH, Lee IT, Hsieh HL, Kou YR, Yang CM: Cigarette smoke extract induces HO-1 expression in mouse cerebral vascular endothelial cells: involvement of c-Src/NADPH oxidase/PDGFR/JAK2/STAT3 pathway. J Cell Physiol. 2010, 225: 741-750. 10.1002/jcp.22270.CrossRefPubMed

12.

Rustemeier K, Stabbert R, Haussmann HJ, Roemer E, Carmines EL: Evaluation of the potential effects of ingredients added to cigarettes. Part 2: chemical composition of mainstream smoke. Food Chem. Toxicol. 2002, 40: 93-104.

13.

Zang LY, Stone K, Pryor WA: Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free Radic Biol Med. 1995, 19: 161-167. 10.1016/0891-5849(94)00236-D.CrossRefPubMed

14.

Carnevali S, Petruzzelli S, Longoni B, Vanacore R, Barale R, Cipollini M, Scatena F, Paggiaro P, Celi A, Giuntini C: Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts. Am J Physiol. 2003, 284: L955-L963.

15.

Hoshino Y, Mio T, Nagai S, Miki H, Ito I, Izumi T: Cytotoxic effects of cigarette smoke extract on an alveolar type II cell-derived cell line. Am J Physiol. 2001, 281: L509-L516.

16.

Misonou Y, Takahashi M, Park YS, Asahi M, Mihyamoto Y, Sakiyama H, Cheng X, Taniguchi N: Acrolein induces Hsp72 via both PKC-δ/JNK and calcium signaling pathways in human umbilical vein endothelial cells. Free Radical Res. 2005, 39: 507-512. 10.1080/10715760500072255.CrossRef

17.

Iles KE, Dickinson DA, Wigley AF, Welty NE, Blank V, Forman HJ: HNE increases HO-1 through activation of the ERK pathway in pulmonary epithelial cells. Free Rad Biol Med. 2005, 39: 355-364. 10.1016/j.freeradbiomed.2005.03.026.PubMedCentralCrossRefPubMed

18.

Zhang H, Forman HJ: Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells. Am J Respir Cell Mol Biol. 2008, 38: 483-490. 10.1165/rcmb.2007-0260OC.CrossRefPubMed

19.

Favatier F, Polla BS: Tobacco-smoke-inducible human haem oxygenase-1 gene expression: role of distinct transcription factors and reactive oxygen intermediates. Biochem J. 2001, 353: 475-482. 10.1042/0264-6021:3530475.PubMedCentralCrossRefPubMed

20.

Mur C, Claria J, Rodela S, Lario S, Campistol JM, Titos E, Inigo P, Cases A, Abian J, Esmatjes E: Cigarette smoke concentrate increases 8-epi-PGF_2α and TGFβ₁ secretion in rat mesangial cells. Life Sci. 2004, 75: 611-621. 10.1016/S0024-3205(04)00289-9.CrossRefPubMed

21.

Nagaraj NS, Zacharias W: Cigarette smoke condensate increases cathepsin-mediated invasiveness of oral carcinoma cells. Toxicol Lett. 2007, 170: 134-145. 10.1016/j.toxlet.2007.02.014.PubMedCentralCrossRefPubMed

22.

Tenhunen R, Marver HS, Schmid R: The enzymatic catabolism of hemoglobin: stimulation of microsomal heme oxygenase by hemin. J Lab Clin Med. 1971, 75: 410-421.

23.

Parinandi NL, Kleinberg MA, Usatyuk PV, Cummings RJ, Pennathur A, Cardounel AJ, Zweier JL, Garcia JG, Natarajan V: Hyperoxia-induced NAD(P)H oxidase activation and regulation by MAP kinases in human lung endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2003, 284: L26-L38.CrossRefPubMed

24.

Wu X, Lu H, Zhou L, Huang Y, Chen H: Changes of phosphatidylcholine-specific phospholipase C in hepatocarcinogenesis and in the proliferation and differentiation of rat liver cancer cells. Cell Biol Int. 1997, 21: 375-381. 10.1006/cbir.1997.0148.CrossRefPubMed

25.

Chavez J, Cano C, Souki A, Bermudez V, Medina M, Ciszek A, Amell A, Vargas ME, Reyna N, Toledo A: Effect of cigarette smoking on the oxidant/antioxidant balance in healthy subjects. Am J Ther. 2007, 14: 189-193. 10.1097/01.psp.0000249918.19016.f6.CrossRefPubMed

26.

Kode A, Yang SR, Rahman I: Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells. Respir Res. 2006, 7: 132-10.1186/1465-9921-7-132.PubMedCentralCrossRefPubMed

27.

Jaimes EA, DeMaster EG, Tian RX, Raij L: Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arterioscler Thromb Vasc Biol. 2004, 24: 1031-1036. 10.1161/01.ATV.0000127083.88549.58.CrossRefPubMed

28.

Stewart AJ, Morgan K, Farquharson C, Millar RP: Phospholipase C-eta enzymes as putative protein kinase C and Ca²⁺ signalling components in neuronal and neuroendocrine tissues. Neuroendoc. 2007, 86: 243-248. 10.1159/000107795.CrossRef

29.

Ryter SW, Choi AM: Heme oxygenase-1: redox regulation of a stress protein in lung and cell culture models. Antioxid Redox Signal. 2005, 7: 80-91. 10.1089/ars.2005.7.80.CrossRefPubMed

30.

Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S: Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest. 1999, 103: 129-135. 10.1172/JCI4165.PubMedCentralCrossRefPubMed

31.

Parfenova H, Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, Leffler CW: Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am J Physiol Cell Physiol. 2006, 290: C1399-C1410.CrossRefPubMed

32.

Nimura T, Weinstein PR, Massa SM, Panter S, Sharp FR: Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. Brain Res Mol Brain Res. 1996, 37: 201-208.CrossRefPubMed

33.

Panahian N, Yoshiura M, Maines MD: Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem. 1999, 72: 1187-1203.CrossRefPubMed

34.

Chiu YC, Fong YC, Lai CH, Hung CH, Hsu HC, Lee TS, Yang RS, Fu WM, Tang CH: Thrombin-induced IL-6 production in human synovial fibroblasts is mediated by PAR1, phospholipase C, protein kinase Cα, c-Src, NF-kappa B and p300 pathway. Mol Immunol. 2008, 45: 1587-1599. 10.1016/j.molimm.2007.10.004.CrossRefPubMed

35.

Rojo AI, Salina M, Salazar M, Takahashi S, Suske G, Calvo V, de Sagarra MR, Cuadrado A: Regulation of heme oxygenase-1 gene expression through the phosphatidylinositol 3-kinase/PKC-ζ pathway and Sp1. Free Radic Biol Med. 2006, 41: 247-261. 10.1016/j.freeradbiomed.2006.04.002.CrossRefPubMed

36.

Ye H, Ma WL, Jin S, Liu SY, Wang DX, Hu QH: Cigarette smoke extract activates PKC isoforms and down-regulates the expressions of potassium channels BK_Ca and Kv1.5 in rat bronchial smooth muscle cells. Sheng Li Xue Bao. 2008, 60: 709-714.PubMed

37.

Cathcart MK: Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis. Arterioscler Thromb Vasc Biol. 2004, 24: 23-28. 10.1161/01.ATV.0000097769.47306.12.CrossRefPubMed

38.

Madamanchi NR, Hakim ZS, Runge MS: Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes. J Thromb Haemost. 2005, 3: 254-267. 10.1111/j.1538-7836.2004.01085.x.CrossRefPubMed

39.

Lagente V, Planquois JM, Leclerc O, Schmidlin F, Bertrand CP: Oxidative stress is an important component of airway inflammation in mice exposed to cigarette smoke or lipopolysaccharide. Clin Exp Pharmacol Physiol. 2008, 35: 601-605. 10.1111/j.1440-1681.2007.04848.x.CrossRefPubMed

40.

Lemjabbar H, Li D, Gallup M, Sidhu S, Drori E, Basbaum C: Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor α-converting enzyme and amphiregulin. J Biol Chem. 2003, 278: 26202-26207. 10.1074/jbc.M207018200.CrossRefPubMed

41.

Fortuño A, Bidegain J, Robador PA, Hermida J, López-Sagaseta J, Beloqui O, Díez J, Zalba G: Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension. Hypertension. 2009, 54: 744-750. 10.1161/HYPERTENSIONAHA.109.129353.CrossRefPubMed

42.

Simon F, Stutzin A: Protein kinase C-mediated phosphorylation of p47 phox modulates platelet-derived growth factor-induced H₂O₂ generation and cell proliferation in human umbilical vein endothelial cells. Endothelium. 2008, 15: 175-188. 10.1080/10623320802174480.CrossRefPubMed

43.

Gutkind JS: Cell growth control by G protein-coupled receptors: from signal transduction to signal integration. Oncogene. 1998, 17: 1331-1342. 10.1038/sj.onc.1202186.CrossRefPubMed

44.

Luttrell LM, Daaka Y, Lefkowitz RJ: Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol. 1999, 11: 177-183. 10.1016/S0955-0674(99)80023-4.CrossRefPubMed

45.

Eguchi S, Iwasaki H, Ueno H, Frank GD, Motley ED, Eguchi K, Marumo F, Hirata Y, Inagami T: Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser⁴¹¹ in vascular smooth muscle cells. Possible requirement of epidermal growth factor receptor, Ras, extracellular signal-regulated kinase, and Akt. J Biol Chem. 1999, 274: 36843-36851. 10.1074/jbc.274.52.36843.CrossRefPubMed

46.

Basbaum C, Li D, Gensch E, Gallup M, Lemjabbar H: Mechanisms by which gram-positive bacteria and tobacco smoke stimulate mucin induction through the epidermal growth factor receptor (EGFR). Novartis Found Symp. 2002, 248: 171-176.CrossRefPubMed

47.

Kietzmann T, Samoylenko A, Immenschuh S: Transcriptional regulation of heme oxygenase-1 gene expression by MAP kinases of the JNK and p38 pathways in primary cultures of rat hepatocytes. J Biol Chem. 2003, 278: 17927-17936. 10.1074/jbc.M203929200.CrossRefPubMed

48.

Yuan X, Xu C, Pan Z, Keum YS, Kim JH, Shen G, Yu S, Oo KT, Ma J, Kong AN: Butylated hydroxyanisole regulates ARE-mediated gene expression via Nrf2 coupled with ERK and JNK signaling pathway in HepG2 cells. Mol Carcinog. 2006, 45: 841-850. 10.1002/mc.20234.CrossRefPubMed

Title: Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells
Authors: Ruey-Horng Shih
Shin-Ei Cheng
Li-Der Hsiao
Yu Ru Kou
Chuen-Mao Yang
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-8-104

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells

Abstract

Background

Objective

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2011

Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats

Increased local concentration of complement C5a contributes to incisional pain in mice

Regulation of Toll-like receptor 1 and -2 in neonatal mice brains after hypoxia-ischemia

Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2

Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α) on phagocytes

Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats