Abstract
Purpose
Heat stress stimulation can cause various injuries in human umbilical vein endothelial cells (HUVEC), including apoptotic cell death and an increase in cell permeability. Propofol (PPF), a commonly used anesthetic, is known to have an important role in antioxidation as well as organ protection. Therefore, our aim is to evaluate the protective effects of PPF on heat stress (HS)-induced oxidative stress injury and its possible mechanism of action.
Methods
For HS + PPF, cells were treated with propofol followed by 2 h heat stress at 43 °C and then 4 h incubation under normal conditions. For propofol treatment, HUVEC were cultured in serum-free Dulbecco’s modified Eagle medium supplemented with 0, 10, 25, or 50 μM propofol for 6 h under normal conditions.
Results
During the study, we found that, in HS-induced cellular damage, the protective effect of propofol was related closely with its antioxidation properties. We further revealed that heat stress significantly reduced the level of manganese superoxide demutase (MnSOD) and Cu/Zn SOD, but that propofol could inhibit the reduction of MnSOD only. Transfection of HUVEC with MnSOD small interfering RNA (siRNA) markedly decreased the expression of MnSOD, and the protective effect of propofol in the MnSOD siRNA clones was significantly reduced.
Conclusion
Propofol protected the heat stress-injured cells, at least partly, through upregulating MnSOD expression, effectively reducing the direct or indirect cell damage caused by oxidative stress.
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References
Bouchama A, Knochel JP. Heat stroke. N Engl J Med. 2002;346(25):1978–88.
Kourtis N, Nikoletopoulou V, Tavernarakis N. Small heat-shock proteins protect from heat-stroke-associated neurodegeneration. Nature (Lond). 2012;490(7419):213–8.
Hemon D, Jougla E. The heat wave in France in August 2003. Rev Epidemiol Sante Publique. 2004;52(1):3–5.
Patz JA, Campbell-Lendrum D, Holloway T, Foley JA. Impact of regional climate change on human health. Nature (Lond). 2005;438(7066):310–7.
McAnulty SR, McAnulty L, Pascoe DD, Gropper SS, Keith RE, Morrow JD, Gladden LB. Hyperthermia increases exercise-induced oxidative stress. Int J Sports Med. 2005;26(3):188–92.
Burdon RH, Gill VM, Rice-Evans C. Oxidative stress and heat shock protein induction in human cells. Free Radic Res Commun. 1987;3(1-5):129–39.
Skibba JL, Powers RH, Stadnicka A, Cullinane DW, Almagro UA, Kalbfleisch JH. Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia. Int J Hyperthermia. 1991;7(5):749–61.
Gu ZT, Wang H, Li L, Liu YS, Deng XB, Huo SF, Yuan FF, Liu ZF, Tong HS, Su L (2014) Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell. Sci Rep 4(4469). doi:10.1038/srep04469.
Kuo JR, Lin CL, Chio CC, Wang JJ, Lin MT. Effects of hypertonic (3%) saline in rats with circulatory shock and cerebral ischemia after heatstroke. Intensive Care Med. 2003;29(9):1567–73.
Bong CL, Lim E, Allen JC, Choo WL, Siow YN, Teo PB, Tan JS (2015) A comparison of single-dose dexmedetomidine or propofol on the incidence of emergence delirium in children undergoing general anaesthesia for magnetic resonance imaging. Anaesthesia 70(4):393–9.
Ozkan D, Akkaya T, Yalcindag A, Hanci T, Gonen E, Gumus H, Delibas N. Propofol sedation in total knee replacement: effects on oxidative stress and ischemia-reperfusion damage. Anaesthesist. 2013;62(7):537–42.
Bruells CS, Maes K, Rossaint R, Thomas D, Cielen N, Bergs I, Bleilevens C, Weis J, Gayan-Ramirez G. Sedation using propofol induces similar diaphragm dysfunction and atrophy during spontaneous breathing and mechanical ventilation in rats. Anesthesiology. 2014;120(3):665–72.
Chen J, Chen W, Zhu M, Zhu Y, Yin H, Tan Z. Propofol attenuates angiotensin II-induced apoptosis in human coronary artery endothelial cells. Br J Anaesth. 2011;107(4):525–32.
Zhu M, Chen J, Tan Z, Wang J. Propofol protects against high glucose-induced endothelial dysfunction in human umbilical vein endothelial cells. Anesth Analg. 2012;114(2):303–9.
Zhang D, Wang Y, Liang Y, Zhang M, Wei J, Zheng X, Li F, Meng Y, Zhu NW, Li J, Wu XR, Huang C. Loss of p27 upregulates MnSOD in a STAT3-dependent manner, disrupts intracellular redox activity and enhances cell migration. J Cell Sci. 2014;127(pt 13):2920–33.
Sun G, Wang Y, Hu W, Li C. Effects of manganese superoxide dismutase (MnSOD) expression on regulation of esophageal cancer cell growth and apoptosis in vitro and in nude mice. Tumour Biol. 2013;34(3):1409–19.
Qian Z, Liu T, Liu Q, He S, Liu Y, Hou F, Wang X, Mi X, Cai C, Liu X. p53 is involved in shrimp survival via its regulation roles on MnSOD and GPx in response to acute environmental stresses. Comp Biochem Physiol C Toxicol Pharmacol. 2014;159:38–51.
Jia L, Dong Y, Yang H, Pan X, Fan R, Zhai L. Serum superoxide dismutase and malondialdehyde levels in a group of Chinese patients with age-related macular degeneration. Aging Clin Exp Res. 2011;23(4):264–7.
Privalle CT, Fridovich I. Induction of superoxide dismutase in Escherichia coli by heat shock. Proc Natl Acad Sci USA. 1987;84(9):2723–6.
Lin YL, Chang HC, Chen TL, Chang JH, Chiu WT, Lin JW, Chen RM. Resveratrol protects against oxidized LDL-induced breakage of the blood–brain barrier by lessening disruption of tight junctions and apoptotic insults to mouse cerebrovascular endothelial cells. J Nutr. 2010;140(12):2187–92.
Li R, Beebe T, Cui J, Rouhanizadeh M, Ai L, Wang P, Gundersen M, Takabe W, Hsiai TK. Pulsatile shear stress increased mitochondrial membrane potential: implication of Mn-SOD. Biochem Biophys Res Commun. 2009;388(2):406–12.
Ortega-Camarillo C, Guzman-Grenfell AM, Garcia-Macedo R, Rosales-Torres AM, Avalos-Rodriguez A, Duran-Reyes G, Medina-Navarro R, Cruz M, Diaz-Flores M, Kumate J. Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells. Mol Cell Biochem. 2006;281(1-2):163–71.
Yamaguchi H, Woods NT, Piluso LG, Lee HH, Chen J, Bhalla KN, Monteiro A, Liu X, Hung MC, Wang HG. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem. 2009;284(17):11171–83.
Cichocki M, Sosnowski M, Jablonowski Z. A giant renal angiomyolipoma (AML) in a patient with septo-optic dysplasia (SOD). Eur J Med Res. 2014;19(1):46.
Matsuki S, Iuchi Y, Ikeda Y, Sasagawa I, Tomita Y, Fujii J. Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline. Biochem Biophys Res Commun. 2003;312(3):843–9.
Dangi SS, Gupta M, Dangi SK, Chouhan VS, Maurya VP, Kumar P, Singh G, Sarkar M (2015) Expression of HSPs: an adaptive mechanism during long-term heat stress in goats (Capra hircus). Int J Biometeorol 59(8):1095–106.
Kennedy D, Mnich K, Samali A. Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM. FEBS Open Bio. 2014;4:813–21.
Belhadj SI, Najar T, Ghram A, Dabbebi H, Ben MM, Abdrabbah M. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int J Hyperthermia. 2014;30(7):513–23.
Bouchama A, Hammami MM, Haq A, Jackson J, Al-Sedairy S. Evidence for endothelial cell activation/injury in heatstroke. Crit Care Med. 1996;24(7):1173–8.
Brinton MR, Tagge CA, Stewart RJ, Cheung AK, Shiu YT, Christensen DA. Thermal sensitivity of endothelial cells on synthetic vascular graft material. Int J Hyperthermia. 2012;28(2):163–74.
Bach LA (2015) Endothelial cells and the IGF system. J Mol Endocrinol 54(1):R1–13.
Urbaczek AC, Ribeiro LC, Ximenes VF, Afonso A, Nogueira CT, Generoso WC, Alberice JV, Rudnicki M, Ferrer R, Fonseca LM, Costa PI. Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure. Mem Inst Oswaldo Cruz. 2014;109(6):748–56.
Wang L, Taneja R, Wang W, Yao LJ, Veldhuizen RA, Gill SE, Fortin D, Inculet R, Malthaner R, Mehta S. Human alveolar epithelial cells attenuate pulmonary microvascular endothelial cell permeability under septic conditions. PLoS ONE. 2013;8(2):e55311.
Jacob AK, Hotchkiss RS, DeMeester SL, Hiramatsu M, Karl IE, Swanson PE, Cobb JP, Buchman TG. Endothelial cell apoptosis is accelerated by inorganic iron and heat via an oxygen radical dependent mechanism. Surgery (St. Louis). 1997;122(2):243–53 (discussion 254).
Farrokh S, Brillen AL, Haendeler J, Altschmied J, Schaal H (2015) Critical regulators of endothelial cell functions: for a change being alternative. Antioxid Redox Signal 22(14):1212–29.
Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol. 2004;286(6):C1213–28.
Gardner TW, Lieth E, Khin SA, Barber AJ, Bonsall DJ, Lesher T, Rice K, Brennan WJ. Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells. Invest Ophthalmol Vis Sci. 1997;38(11):2423–7.
Xiao G, Tang L, Yuan F, Zhu W, Zhang S, Liu Z, Geng Y, Qiu X, Zhang Y, Su L. Eicosapentaenoic acid enhances heat stress-impaired intestinal epithelial barrier function in Caco-2 cells. PLoS ONE. 2013;8(9):e73571.
Hsu YL, Yu HS, Lin HC, Wu KY, Yang RC, Kuo PL. Heat shock induces apoptosis through reactive oxygen species involving mitochondrial and death receptor pathways in corneal cells. Exp Eye Res. 2011;93(4):405–12.
Guan L, Han B, Li Z, Hua F, Huang F, Wei W, Yang Y, Xu C. Sodium selenite induces apoptosis by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in human acute promyelocytic leukemia NB4 cells. Apoptosis. 2009;14(2):218–25.
Strassburger M, Bloch W, Sulyok S, Schuller J, Keist AF, Schmidt A, Wenk J, Peters T, Wlaschek M, Lenart J, Krieg T, Hafner M, Kumin A, Werner S, Muller W, Scharffetter-Kochanek K. Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo. Free Radic Biol Med. 2005;38(11):1458–70.
Kirby K, Hu J, Hilliker AJ, Phillips JP. RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress. Proc Natl Acad Sci USA. 2002;99(25):16162–7.
Tsuchiya M, Asada A, Maeda K, Ueda Y, Sato EF, Shindo M, Inoue M. Propofol versus midazolam regarding their antioxidant activities. Am J Respir Crit Care Med. 2001;163(1):26–31.
Tang J, Deng P, Jiang Y, Tang Y, Chen B, Su L, Liu Z. Role of HMGB1 in propofol protection of rat intestinal epithelial cells injured by heat shock. Cell Biol Int. 2013;37(3):262–6.
Acknowledgments
This study was supported by Guangdong Province natural science foundation research project team (No. S2013030013217), National Nature Science Fund of China (No. 81501690), supported by Guangdong Natural Science Foundation of China (No. 2015A030310084), and supported by Science and Technology Planning Project of Guangdong Province, China (No. 2014A020212490) and Certificate of China Postdoctoral Science Foundation Grant (No. 2015M582397).
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F. Wu, X.J. Dong, H.Q. Zhang, and L. Li contributed equally to this work.
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Wu, F., Dong, X.J., Zhang, H.Q. et al. Role of MnSOD in propofol protection of human umbilical vein endothelial cells injured by heat stress. J Anesth 30, 410–419 (2016). https://doi.org/10.1007/s00540-015-2129-2
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DOI: https://doi.org/10.1007/s00540-015-2129-2