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http://dx.doi.org/10.5352/JLS.2017.27.11.1349

The Ca2+-activated K+ (BK) Channel-opener NS 1619 Prevents Hydrogen Peroxide-induced Cell Death and Mitochondrial Dysfunction in Retinal Pigment Epithelial Cells  

Kang, Jae Hoon (Department of Physiology, Pusan National University School of Medicine)
Woo, Jae Suk (Department of Physiology, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.27, no.11, 2017 , pp. 1349-1356 More about this Journal
Abstract
Potassium channel openers (KCOs) produce physiological and pharmacological defense mechanisms against cell injuries caused by oxidative stress of diverse origins. Openings of mitochondrial and plasmalemmal $K^+$ channels are involved in the defense mechanisms. This study tested whether NS 1619, an opener of large-conductance BK channels, has a similar beneficial influence on the pigment epithelial cells of retinas. The human retinal pigment epithelial cell line ARPE-19 was exposed to $H_2O_2$-induced oxidative stress in the absence and presence of NS 1619. The degrees of the cells' injuries were assessed by analyzing the cells' trypan-blue exclusion abilities and TUNEL staining. NS 1619 produced remarkable protections against cell injuries caused by $H_2O_2$. It prevented apoptotic and necrotic cell deaths. The protective effect of NS 1619 was significantly diminished when the cells were treated with NS 1619 in combination with the BK channel-blocker paxilline. NS 1619 significantly ameliorated cellular ATP deprivations in $H_2O_2$-treated cells. It helped mitochondria preserve their functional integrity, which was estimated by their MTT reduction abilities and mitochondrial membrane potential. In conclusion, it was suggested that NS 1619 had a beneficial effect on mitochondria in regards to preserving their functional integrity under oxidative stress, and it produces defense mechanisms against oxidant-induced cell injuries in ARPE-19 cells.
Keywords
Cell death; KCOs; mitochondria; oxidative stress; RPE cells;
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1 Daut, J., Maier-Rudolph, W., von Beckerath, N., Mehrke, G., Gunther, K. and Goedel-Meinen, L. 1990. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science 247, 1341-1344.   DOI
2 Duty, S. and Weston, A. H. 1990. Potassium channel openers. Pharmacological effects and future uses. Drugs 40, 785-791.   DOI
3 Edwards, G., Niederste-Hollenberg, A., Schneider, J., Noack, T., and Weston, A. H. 1994. Ion channel modulation by NS 1619, the putative BKCa channel opener, in vascular smooth muscle. Br. J. Pharmacol. 113, 1538-1547.   DOI
4 Edwards, G. and Weston, A. H. 1990. Structure-activity relationships of $K^{+}$ channel openers. Trends. Pharmacol. Sci. 11, 417-422.   DOI
5 Farber, J. L., Kyle, M. E. and Coleman, J. B. 1990. Mechanisms of cell injury by activated oxygen species. Lab. Invest. 62, 670-679.
6 Foster, C. D., Fujii, K., Kingdon, J. and Brading, A. F. 1989. The effect of cromakalim on the smooth muscle of the guinea-pig urinary bladder. Br. J. Pharmacol. 97, 281-291.   DOI
7 Gaspar, T., Katakam, P., Snipes, J. A., Kis, B., Domoki, F., Bari, F. and Busija, D. W. 2008. Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels. J. Neurochem. 105, 1115-1128.   DOI
8 Gunter, T. E., Gunter, K. K., Sheu, S. S. and Gavin, C. E. 1994 Mitochondrial calcium transport: physiological and pathological relevance. Am. J. Physiol. 267, C313-C339.   DOI
9 Hagar, H., Ueda, N. and Shah, S. V. 1996. Endonuclease induced DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells. Kidney Int. 49, 355-361.   DOI
10 Inoue, I., Nagase, H., Kishi, K. and Higuti, T. 1991. ATP-sensitive $K^{+}$ channel in the mitochondrial inner membrane. Nature 352, 244-247.   DOI
11 Murray, M. A., Boyle, J. P. and Small, R. C. 1989. Cromakalim-induced relaxation of guinea-pig isolated trachealis: antagonism by glibenclamide and by phentolamine. Br. J. Pharmacol. 98, 865-874.   DOI
12 Kersten, J. R., Gross, G. J., Pagel, P. S. and Warltier, D. C. 1998. Activation of adenosine triphosphate-regulated potassium channels: mediation of cellular and organ protection. Anesthesiology 88, 495-513.   DOI
13 Latorre, R., Castillo, K., Carrasquel-Ursulaez, W., Sepulveda, R. V., Gonzalez-Nilo, F., Gonzalez, C. and Alvarez, O. 2017. Molecular determinants of BK channel functional diversity and functioning. Physiol. Rev. 97, 39-87.   DOI
14 Lemasters, J. J., Nieminen, A. L., Qian, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A. and Herman, B. 1998. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta 1366, 177-196.   DOI
15 Lyman, G. E. and DeVincenzo, J. P. 1967. Determination of picogram amounts of ATP using the luciferin-luciferase enzyme system. Anal. Biochem. 21, 435-443.   DOI
16 Morgan, D. M. 1998. Tetrazolium (MTT) assay for cellular viability and activity. Methods. Mol. Biol. 79, 179-183.
17 Murry, C. E., Jennings, R. B. and Reimer, K. A. 1986. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136.   DOI
18 Robertson, D. W. and Steinberg, M. I. 1990. Potassium channel modulators: scientific applications and therapeutic promise. J. Med. Chem. 33, 1529-1541.   DOI
19 Schwartzman, R. A. and Cidlowski, J. A. 1993. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr. Rev. 14, 133-151.
20 Bentzen, B. H., Olesen, S. P., Ronn, L. C. and Grunnet, M. 2014. BK channel activators and their therapeutic perspectives. Front. Physiol. 5, 389.
21 Bjorkerud, S. and Bondjers, G. 1972. Endothelial integrity and viability in the aorta of the normal rabbit and rat as evaluated with dye exclusion tests and interference contrast microscopy. Atherosclerosis 15, 285-300.   DOI
22 Clarke, P. G. 1990. Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol. 181, 195-213.
23 Cole, W. C., McPherson, C. D. and Sontag, D. 1991. ATPregulated $K^{+}$ channels protect the myocardium against ischemia/reperfusion damage. Circ. Res. 69, 571-581.   DOI
24 Szewczyk, A. and Marban, E. 1999. Mitochondria: a new target for $K^{+}$ channel openers? Trends Pharmacol. Sci. 20, 157-161.   DOI
25 Sparrow, J. R., Hicks, D. and Hamel, C. P. 2010. The retinal pigment epithelium in health and disease. Curr. Mol. Med. 10, 802-823.   DOI
26 Standen, N. B., Quayle, J. M., Davies, N. W., Brayden, J. E., Huang, Y. and Nelson, M. T. 1989. Hyperpolarizing vasodilators activate ATP-sensitive $K^{+}$ channels in arterial smooth muscle. Science 245, 177-180.   DOI
27 Stern, J. and Temple, S. 2015. Retinal pigment epithelial cell proliferation. Exp. Biol. Med (Maywood). 240, 1079-1986.   DOI
28 Testai, L., Rapposelli, S. and Calderone, V. 2007. Cardiac ATP- sensitive potassium channels: a potential target for an anti-ischaemic pharmacological strategy. Cardiovasc. Hematol. Agents. Med. Chem. 5, 79-90.   DOI
29 Testai, L., Rapposelli, S., Martelli, A., Breschi, M. C. and Calderone, V. 2015. Mitochondrial potassium channels as pharmacological target for cardioprotective drugs. Med. Res. Rev. 35, 520-553.   DOI
30 Vakifahmetoglu-Norberg, H. Ouchida, A. T. and Norberg, E. 2017. The role of mitochondria in metabolism and cell death. Biochem Biophys. Res. Commun. 482, 426-431.   DOI
31 Wimmers, S., Karl, M. O. and Strauss, O. 2007. Ion channels in the RPE. Prog. Retin. Eye. Res. 26, 263-301.   DOI