Effect of Cigarette Smoke on Rhoa/Rho-Kinase Signalization Pathway in Lung

Yıl 2017, Cilt: 8 Sayı: 30, 35 - 40, 01.06.2017

Harun Alp

https://doi.org/10.17944/mkutfd.323343

Öz

Cigarrette
smoke exposure has side effects on lungs, cardiovascular systems and some tissue
and organs. Rho/rho-kinase signalization pathway has important role bronchial
smooth muscle contractions and cancer development of lung fibroblast. Mechanism
of molecular of some side effects due to cigarette smoke exposure has not yet
been clearly identified. In the present study we aimed to research effect of
cigarette smoke exposure on rho/rho-kinase signalization pathway in lungs. For
this propose mice (male age: 8 weeks) separated into two groups as control and
smoke exposured. The cigarette smoke application continued 7 days in a week
during two mouths. In the end of two mounts, Mice were sacrified by cervical
dislocation and their lungs were isolated. Then rhoA and rho-kinase enzymes
expression and rho-kinase enzyme activity have been determined. Cigarette smoke
exposure caused unregulated rhoA and rho-Kinase enzyme expression and elevated
rho-kinase enzyme activity. As a result cigarette smoke  exposure elevated activity of rho/rho-kinase
signalization pathway.

Anahtar Kelimeler

Cigarette smoke, rhoA, rho-kinase, lung, mice

Akciğerde Rhoa/Rho-Kinaz Sinyalizasyon Yolu Üzerine Sigara İçmenin Etkisi

Öz

Sigara
dumanına maruziyet akciğerler, kalp-damar sistemi ve bazı doku ve organlar
üzerine yan etkilere sahiptir. Rho/rho-kinaz sinyalizasyon yolu bronş düz kas
kasılmaları ve akciğer fibroblast kanseri gelişmesi üzerine önemli role
sahiptir. Sigara dumanına maruz kalmadan dolayı, bazı yan etkilerin moleküler
mekanizması henüz net olarak açıklanamamıştır. Bu çalışmada akciğerlerde
rho/rho-kinaz sinyalizasyon yolunun üzerinde sigara dumanı maruziyetinin
etkisini araştırmayı amaçladık. Bu amaçla fareleri (erkek, yaş: 8 hafta);  kontrol ve sigara dumanına maruz olarak iki
gruba ayırdık. Sigara dumanı uygulaması iki ay boyunca haftada 7 gün şeklinde
devam etti. İki ayın sonunda, fareler servikal dislokasyon ile sakrifiye edildi
ve akciğerleri izole edildi. Daha sonra RhoA ve Rho-kinaz enzimlerin
ekspresyonu ve Rho-kinaz enzimi aktivitesi belirlendi. Sigara dumanı maruziyeti
düzensiz RhoA ve rho-kinaz enzimi aktivitesinde artışa neden oldu. Sonuç
olarak; Sigara dumanı maruziyeti rho/rho-kinaz sinyalizasyon yolunun
aktivitesini arttırdı.

Anahtar Kelimeler

Sigara dumanı, RhoA, rho-kinaz, akciğer, fareler

Kaynakça

• 1- Barua RS, Ambrose JA, Reynolds LJE, DeVoe MC, Zervas JG, Saha DC. Heavy and light cigarette smokers have similar dysfunction of endothelial vasoregulatory activity. Journal of the American College of Cardiology. 2002; 758–1763.
• 2- Tell GS, Polak JF, Ward BJ, Kittner SJ, Savage PJ, Robbins J. Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study (CHS) Collaborative Research Group. Circulation. 1994; 90: 2905–2908.
• 3- Jonas MA, Oates JA, Ockene JK, Hennekens CH. Statement on smoking and cardiovascular disease for health care professionals. Circulation. 1992; 86: 1664–1669.
• 4- Smith CJ, Fischer TH. Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction. Atherosclerosis. 2001; 158: 257–267.
• 5- Tsuchiya M, Asada A, Kasahara E, Sato EF, Shindo M, Inoue M. Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation. 2002; 105: 1155-1157.
• 6- Zhang WZ, Venardos K, Chin-Dusting J, Kaye DM. Adverse effects of cigarette smoke on NO bioavailability: role of arginine metabolism and oxidative stress. Hypertension. 2006; 48, 278-285.
• 7- Guo X, Oldham MJ, Kleinman MT, Phalen RF, Kassab GS. Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries. Am J Physiol Heart Circ Physiol. 2006; 291: 2354-2361.
• 8- Li T, Molteni A, Latkovich P, Castellani W, Baybutt RC. Vitamin A depletion induced by cigarette smoke is associated with the development of emphysema in rats. J Nutr. 2003; 133: 2629-2634.
• 9- Tanriverdi H, Evrengul H, Kuru O, Tanriverdi S, Seleci D, Enli Y, Kaftan HA, Kilic M. Cigarette smoking induced oxidative stress may impair endothelial function and coronary blood flow in angiographically normal coronary arteries. Circ J. 2006; 70: 593-599.
• 10- Conklin BS, Surowiec SM, Ren Z, Li JS, Zhong DS, Lumsden AB, Chen C. Effects of nicotine and cotinine on porcine arterial endothelial cell function. J Surg Res. 2001; 95: 23-31.
• 11- Fukata Y, Amano M and Kaubuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci. 2001; 22: 32-39.
• 12- Miao L, Calvert JW, Tang J et al. Upregulation of small GTPase RhoA in the basilar artery from diabetic (mellitus) rats. Life Sci; 2002; 71:1175-85.
• 13- Miao L, Dai Y, Zhang J. Mechanism of RhoA/Rho kinase activation in endothelin-1-induced contraction in rabbit basilar artery. Am J Physiol. 2002; 283; 983-989.
• 14- Boettner B, Aelst LV. The role of Rho GTPases in disease development. Gene. 2002; 286: 155-174.
• 15- Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science. 1996; 273: 245-248.
• 16- Chitaley K, Webb RC. Microtubule depolymerization facilitates contraction of rat aorta via activation of Rho-kinase. Vasc Pharmacol, 2002; 38: 157-161.
• 17- Büyükafşar K, Levent A. Involvement of Rho/Rho-kinase signalling in the contractile activity and neurotransmitter release in the mouse gastric fundus. Biochem. Biophys. Res. Commun. 2003; 303: 777– 781.
• 18- Büyükafşar K, Ün İ. Effects of the Rho-kinase inhibitors, Y-27632 and fasudil on the corpus cavernosum from diabetic mice. Eur. J. Pharmacol. 200; 472: 235-238.
• 19. Büyükafşar K, Levent, A, Ark M. Expression of Rho-kinase and its functional role in the contractile activity of mouse vas deferens. Br. J. Pharmacol. 2003; 140: 743– 749.
• 20. Mukai Y, Shimokawa H, Mataba T et al. Involvement of Rho-kinase in hypertansive vascular disease novel therapeutic target in hypertension. The FASEB J. 2001; 10.1096/00-0735.
• 21. Berro AI, Jia S, Omaha T, NE B. Cigarette Smoke Extract Exposure Up-regulates the Expression of RhoA Pathway in Murine Airways. J Allergy Clın Immunol . 2011; 127.
• 22. Aghajanian A1, Wittchen ES, Campbell SL, Burridge K. Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motif. PLoS One. 2009; 26:8045.
• 23. Knock GA1, Snetkov VA, Shaifta Y, Connolly M, Drndarski S, Noah A, Pourmahram GE, Becker S, Aaronson PI, Ward JP. Superoxide constricts rat pulmonary arteries via Rho-kinase-mediated Ca(2+) sensitization. Free Radic Biol Med. 2009; 1: 633-642.
• 24. Coleman ML, Sahai AE, Yeo M, Bosch M, Dewar A, Olsan MF. Mambrane blebbing during apoptosis result from caspase-3-madiated activation of ROCK I. Nat Cell Biol. 2001; 3, 339-45.
• 25. Sebbagh M, Hamelin J, Riche N, Bertoglio J, Breard J. Caspase-3-madiated cleavage of ROCK I induced MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Bio. 2001; 3:346-52.
• 26. Yang X, Zheng F, Zhang S, Lu J. Loss of RhoA expression prevents proliferation and metastasis of SPCA1 lung cancer cells in vitro. Biomed Pharmacother. 2015; 69: 361-366.
• 27. Li B, Zhao WD, Tan ZM, Fang WG, Zhu L, Chen YH. Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett. 2006; 24: 4252-4260
• 28. Hallgren O1, Rolandsson S, Andersson-Sjöland A, Nihlberg K, Wieslander E, Kvist-Reimer M, Dahlbäck M, Eriksson L, Bjermer L, Erjefält JS, Löfdahl CG, Westergren-Thorsson G. Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients. J Transl Med. 2012; 22: 171.