Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Protective Effects of Verapamil against H2O2-Induced Apoptosis in Human Lens Epithelial Cells

  • Wang, Zhuo (Department of Pharmacology, HE's University) ;
  • Wang, Dan (Department of Pharmacology, HE's University) ;
  • Li, Yan (Experimental Teaching Center of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University) ;
  • Zhang, Xiuli (School of Pharmaceutical Sciences, Binzhou Medical University)
  • Received : 2014.03.20
  • Accepted : 2014.08.14
  • Published : 2014.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Verapamil is used in the treatment of hypertension, angina pectoris, and atrial fibrillation. Recently, several studies have demonstrated that verapamil increased the optic nerve head blood flow and improved the retrobulbar circulation. All these show that verapamil is potentially useful for ophthalmic treatment. Thus, the aim of this study is to investigate whether verapamil could protect human lens epithelial cell (HLEC) from oxidative stress induced by $H_2O_2$ and the cellular mechanism underlying this protective function. The viability of HLEC was determined by the MTT assay and apoptotic cell death was analyzed by Hoechst 33258 staining. Moreover, Caspase-3 expression was detected by immunocytochemistry and flow cytometry analysis. We also detected Caspase-3 mRNA expression by reverse-transcription-polymerase chain reaction and the GSH content in cell culture. The results showed that oxidative stress produced significant cell apoptotic death and it was reduced by previous treatment with the verapamil. Verapamil was effective in reducing HLEC death mainly through reducing the expression level of apoptosis-related proteins, caspase-3, and increasing glutathione content. Therefore, it was suggested that verapamil was effective in reducing HLEC apoptosis induced by $H_2O_2$.

Keywords

References

  1. Bhuyan, K. C., Bhuyan, D. K. and Podos, S. M. (1986) Lipid peroxidation in cataract of the human. Life Sci. 38, 1463-1471. https://doi.org/10.1016/0024-3205(86)90559-X
  2. Cheng, G., Shan, J., Xu, G., Huang, J., Ma, J., Ying, S. and Zhu, L. (2003) Apoptosis induced by simvastatin in rat vascular smooth muscle cell through $Ca^{2+}$-calpain and caspase-3 dependent pathway. Pharmacol. Res. 48, 571-578. https://doi.org/10.1016/S1043-6618(03)00245-7
  3. Foster, A. (1999) Cataract - A global perspective: output, outcome and outlay. Eye 13, 449-453. https://doi.org/10.1038/eye.1999.120
  4. Fukui, H. N. (1976) The effect of hydrogen peroxide on the rubidium transport of the rat lens. Exp. Eye Res. 23, 595-596. https://doi.org/10.1016/0014-4835(76)90217-7
  5. Imlay, J. A. and Linn, S. (1988) DNA damage and oxygen radical toxicity. Science 240,1302-1309. https://doi.org/10.1126/science.3287616
  6. Kalonia, H., Kumar, P. and Kumar, A. (2011) Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats. Brain Res. 1372, 115-126 https://doi.org/10.1016/j.brainres.2010.11.060
  7. Keppler, D. (1999) Export pumps for glutathione S-conjugates. Free Radic. Biol. Med. 27, 985-991. https://doi.org/10.1016/S0891-5849(99)00171-9
  8. Li, W. C., Kuszak, J. R., Dunn, K., Wang, R. R., Ma, W., Wang, G. M., Spector, A., Leib, M., Cotliar, A. M. and Weiss, M. et al. (1995) Lens epithelial cell apoptosis appears to be a common cellular basis for noncongenital cataract development in humans and animals. J. Cell Biol. 130, 169-181. https://doi.org/10.1083/jcb.130.1.169
  9. Nagashima, H. and Goto, T. (2000) Calcium channel blockers verapamil and diltiazem impaired rubratoxin B-caused toxicity in HL60 cells. Toxicol. Lett. 118, 47-51. https://doi.org/10.1016/S0378-4274(00)00266-6
  10. Naval, M. V., Gomez-Serranillos, M. P., Carretero, M. E. and Villar, A. M. (2007) Neuroprotective effect of a ginseng (Panax ginseng) root extract on astrocytes primary culture. J. Ethnopharmacol. 112, 262-270. https://doi.org/10.1016/j.jep.2007.03.010
  11. Netland, P. A., Feke, G. T., Konno, S., Goger, D. G. and Fujio, N. (1996) Optic nerve head circulation after topical calcium channel blocker. J. Glaucoma 5, 200-206.
  12. Netland, P. A., Grosskreutz, C. L., Feke, G. T. and Hart, L. J. (1995) Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker. Am. J.Ophthalmol. 119, 694-700. https://doi.org/10.1016/S0002-9394(14)72772-2
  13. Ottonello, S., Foroni, C., Carta, A., Petrucco, S. and Maraini, G. (2000) Oxidative stress and age-related cataract. Ophthalmologica 214, 78-85. https://doi.org/10.1159/000027474
  14. Resnikoff, S., Pascolini, D., Etya'ale, D., Kocur, I., Pararajasegaram, R., Pokharel, G. P. and Mariotti, S. P. (2004) Global data on visual impairment in the year 2002. Bull World Health Organ. 82, 844-851.
  15. Richer, S. P. and Rose, R. C. (1998) Water soluble antioxidants in mammalian aqueous humor: interaction with UV B and hydrogen peroxide. Vision Res. 38, 2881-2888. https://doi.org/10.1016/S0042-6989(98)00069-8
  16. Spector, A., Huang, R. C. and Wang, G. M. (1985) The effect of $H_2O_2$ on lens epithelial cell glutathione. Curr. Eye Res. 4, 1289-1295. https://doi.org/10.3109/02713688509017689
  17. Spector, A. and Garner, W. H. (1981) Hydrogen peroxide and human cataract. Exp. Eye Res. 33, 673-681. https://doi.org/10.1016/S0014-4835(81)80107-8
  18. Spector, A. (1995) Oxidative stress induced cataract: mechanism of action. FASEB J. 9, 1173-1182. https://doi.org/10.1096/fasebj.9.12.7672510
  19. Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456-1462. https://doi.org/10.1126/science.7878464
  20. Truscott, R. J. and Augusteyn, R. C. (1977) Oxidative changes in human lens proteins during senile nuclear cataract formation. Biochim. Biophys. Acta 492, 43-52. https://doi.org/10.1016/0005-2795(77)90212-4
  21. Wakamatsu, T. H., Dogru, M. and Tsubota, K. (2008) Tearful relations: oxidative stress, inflammation and eye diseases. Arq. Bras. Oftalmol. 71, 72-79. https://doi.org/10.1590/S0004-27492008000700015

Cited by

  1. Protective effect of berberine against oxidative stress-induced apoptosis in rat bone marrow-derived mesenchymal stem cells vol.12, pp.6, 2016, https://doi.org/10.3892/etm.2016.3866
  2. 1118-20, an indazole diarylurea compound, inhibits hepatocellular carcinoma HepG2 proliferation and tumour angiogenesis involving Wnt/β-catenin pathway and receptor tyrosine kinases vol.67, pp.10, 2015, https://doi.org/10.1111/jphp.12440
  3. Neuroprotective effects of Aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion vol.33, pp.5, 2015, https://doi.org/10.3233/RNN-150509
  4. Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion vol.20, pp.5, 2016, https://doi.org/10.4196/kjpp.2016.20.5.515
  5. Anti-apoptotic effect of modified Chunsimyeolda-tang, a traditional Korean herbal formula, on MPTP-induced neuronal cell death in a Parkinson's disease mouse model vol.176, 2015, https://doi.org/10.1016/j.jep.2015.11.013
  6. Apoptosis or senescence? Which exit route do epithelial cells and fibroblasts preferentially follow? vol.156, 2016, https://doi.org/10.1016/j.mad.2016.03.010
  7. Protection afforded by quercetin against H2O2-induced apoptosis on PC12 cells via activating PI3K/Akt signal pathway vol.36, pp.1, 2016, https://doi.org/10.3109/10799893.2015.1049363
  8. Comparative effects of calcium and potassium channel modulators on ischemia/reperfusion injury in the isolated rat heart pp.1573-4919, 2018, https://doi.org/10.1007/s11010-018-3384-y
  9. Eaf2 protects human lens epithelial cells against oxidative stress-induced apoptosis by Wnt signaling vol.17, pp.2, 2014, https://doi.org/10.3892/mmr.2017.8246
  10. Novel Combination of Alprostadil-D-tocopheryl Polyethylene Glycol Succinate for Treatment of Erectile Dysfunction vol.15, pp.6, 2014, https://doi.org/10.3923/ijp.2019.738.744
  11. Cordycepin Exerts Neuroprotective Effects via an Anti-Apoptotic Mechanism based on the Mitochondrial Pathway in a Rotenone-Induced Parkinsonism Rat Model vol.18, pp.8, 2014, https://doi.org/10.2174/1871527318666190905152138
  12. Knockdown of Tripartite motif-containing 22 (TRIM22)relieved the apoptosis of lens epithelial cells by suppressing the expression of TNF receptor-associated factor 6 (TRAF6) vol.12, pp.1, 2014, https://doi.org/10.1080/21655979.2021.1980645