Cigarette smoke extract activates PKC isoforms and down-regulates the expressions of potassium channels BKCa and Kv1.5 in rat bronchial smooth muscle cells

( views:69, downloads:0 )
Author:
YE Hong(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
MA Wan-Li(Department of Pathophysiology Department of Respiratory Medicine in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China)
JIN Si(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
LIU Sheng-Yuan(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
WANG Di-Xun(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
HU Qing-Hua(Department of Pathophysiology Key Laboratory of Pulmonary Diseases, Ministry of Health of China)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 60, Issue 06, 2008
DOI:
Key Word:
bronchus;myocyte;cigarette smoke extract;potassium channel;protein kinase C

Abstract: Large-conductance calcium-activated potassium channel (BKCa) and voltage-gated potassium channel Kv 1.5 play an important role in the pathogenesis of bronchial hyperresponsiveness (BHR). It is known that cigarette smoke can induce BHR, however, the role of BKCa and Kv1.5 expression in it remains to be further elucidated. The purpose of the present study was to investigate the direct effects of cigarette smoke extract (CSE) on BKCa and Kv1.5 expression, and the role of protein kinase C (PKC) isoforms activation in primary cultured rat bronchial smooth muscle cells (BSMCs). Primarily cultured rat BSMCs were treated with 5% CSE, the expression and translocation of PKC isoforms were measured by Western blot, and the mRNA and protein levels of BKCa and Kv1.5 a-subunits were determined by semi-quantitative RT-PCR and Western blot, respectively. The results showed that 5% CSE induced the translocation of PKCε, PKη, PKCθ from soluble fraction to particulate fraction, and reduced mRNA and protein expressions of BKCa and Kv1.5 a-subunits. The decreased expression of potassium channels was partly restored by PKC inhibitor, BIM or Goe6983. In summary, CSE may activate PKC isoforms ε,η,θ, thereby down-regulate the expressions of BKCa and Kv1.5 in BSMCs.

  • [1]Wang DX (王迪浔).Advance of airway hyperresponsiveness.Chin Int J Med (中华国际医学杂志) 2003; 3:148-151 (Chinese).
  • [2]Ye H,Ma WL,Yang ML,Liu SY,Wang DX.Effect of chronic cigarette smoking on large-conductance calcium-activated potas-sium channel and Kv 1.5 expression in bronchial smooth muscle ceils of rats.Acta Physiol Sin (生理学报) 2004; 56:573-578.
  • [3]Liu XS,Xu YJ,Zhang ZX,Ni W,Chen SX.Effect of protein kinase C on Kv channel in rat bronchial smooth muscle.Acta Physiol Sin (生理学报) 2003; 55:135-141.
  • [4]Kashyap R,Floreani AA,Heires A J,Sanderson SD,Wyatt TA.Protein kinase C-alpha mediates cigarette smoke extract-and complement factor 5a-stimulated intedeukin-8 release in human bronchial epithelial cells.J Investig Med 2002; 50:46-53.
  • [5]Molnar GA,Wagner Z,Mohas M,Cseh J,Fekete A,Wittmann I.Cigarette smoke-induced alterations in endothelial nitric oxide synthase phosphorylation:role of protein kinase C.Endothe-lium 2007; 14:245-255.
  • [6]Hu J,Xu YJ,Zhang ZX,Tian F.Effect of cigarette smoke extract on proliferation of rat pulmonary artery smooth muscle cells and the relevant roles of protein kinase C.Chin Med J (Engl) 2007;120:1523-1528.
  • [7]Hirst SJ.Airway smooth muscle cell culture:application to stud-ies of airway wall remodeling and phenotype plasticity in asthma.Eur Respir J 1996; 9:808-820.
  • [8]Su Y,Han W,Giraldo C,De Li Y,Block ER.Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery en-dothelial cells.Am J Respir Cell Mol Biol 1998; 19:819-825.
  • [9]Resnik E,Herron J,Fu R,Ivy DD,Cornfield DN.Oxygen ten-sion modulates the expression of pulmonary vascular BKCa chan-nel alpha-and beta-subunits.Am J Physiol Lung Cell Mol Physiol 2006; 290:L761-L768.
  • [10]Wu SN,Wang YJ,Lin MW.Potent stimulation of large-conduc-tance Ca2+-activated K+ channels by rottlerin,an inhibitor of protein kinase C-delta,in pituitary tumor (GH3) cells and in cortical neuronal (HCN-IA) cells.J Cell Physio12007; 210:655-666.
  • [11]Zhu S,White RE,Barman SA.Effect of PKC isozyme inhibition on forskolin-induced activation of BKCa channels in rat pulmo-nary arterial smooth muscle.Lung 2006; 184:89-97.
  • [12]Barman SA,Zhu S,White RE.Protein kinase C inhibits BKCa channel activity in pulmonary arterial smooth muscle.Am J Physiol Lung Cell Mol Physiol 2004; 286:L149-L155.
  • [13]Wu BN,Chen CF,Hong YR,Howng SL,Lin YL,Chen IJ.Activation of BKCa channels via cyclic AMP-and cyclic GMP-dependent protein kinases by eugenosedin-A in rat basilar artery myocytes.Br J Pharmacol 2007; 152:374-385.
  • [14]Roh S,Choi S,Lim I.Involvement of protein kinase A in nitric oxide stimulating effect on a BKCa channel of human dermal fibroblasts.J Invest Dermatol 2007; 127:2533-2538.
  • [15]Liu X,Xu Y,Zhang Z.Changes in delayed rectifier K+ channel function and its regulation by protein kinase C pathway in bron-chial myocytes from asthmatic rats.Chin Med J (Engl) 2003;116:1799-1803.
  • [16]Moreno L,Frazziano G,Cogolludo A,Cobefio L,Tamargo J,Perez-Vizcalno F.Role of protein kinase C zeta and its adaptor protein p62 in voltage-gated potassium channel modulation in pulmonary arteries.Moi Pharmacol 2007; 72:1301-1309.
  • [17]Budhiraja S,Singh J.Protein kinase C beta inhibitors:a new therapeutic target for diabetic nephropathy and vascular complications.Fundam Clin Pharmaco12008; 22:231-240.
  • [18]Allen-Gipson DS,Fioreani AA,Heires AT,Sanderson SD,MacDonald RG,Wyatt TA.Cigarette smoke extract increases C5a receptor expression in human bronchial epithelial cells.J Pharmacol Exp Ther 2005; 314:476-482.
  • [19]Wyatt TA,Kharbanda KK,Tuma DJ,Sisson JH.Malond-ialdehyde -acetaldehyde-adducted bovine serum albumin acti-vates protein kinase C and stimulates interleukin-8 release in bovine bronchial epithelial cells.Alcohol 2001; 25(3):159-166.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn