Influence of sex hormones on DNA content and cystathionine-γ-lyase expression in rat myocardium

Authors

  • A. V. Melnik National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • N. V. Zaichko National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • I. L. Chereshnyuk National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • О. А. Khodakіvskyi National Pirogov Memorial Medical University, Vinnytsia, Ukraine,
  • O. А. Haiduk National Pirogov Memorial Medical University, Vinnytsia, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2017.6.114693

Keywords:

cell cycle, DNA, heart, cystathionine-gamma-lyase expression, hydrogen sulfide

Abstract

Till now sexual features of cystathionine-γ-lyase/H2S system functioning in heart and its relationship to DNA content in myocardial cells nuclei depending on the level of sex hormones.

The aim of this work was to evaluate the effect of sex hormones different levels on DNA fragmentation, indicators of cell cycle, cystathionine-γ-lyase expression and H2S content in heart in male and female rats.

Materials and мethods. The experiments were performed on 40 white laboratory rats of both sexes. Deficiency of sex hormones in the organism of rats was created by castration (ovariectomy and testectomy respectively to female and male rats) with surgical method. Estradiol and testosterone in blood plasma of the animals were determined by immunoenzyme method. DNA level in myocardial cells nuclei was determined by flow DNA cytometry. Cystathionine-γ-lyase gene expression was determined by real time polymerase chain reaction in (Real-time PCR). H2S content in heart was evaluated by spectrophotometry. Statistical processing of the obtained results was performed using standard methods by applying the software package MS Excel and Statistica SPSS 10.0 for Windows.

Results. It has been found that in male rats expression of cystathionine-γ-lyase and H2S content in myocardium were significantly lower, by 46.9 and 16.1 % (p < 0.05) respectively, than in female rats. Along with this, males had greater activity of apoptosis, proliferation and polyploidization compared to females. Gonadectomy in males reduced expression of cystathionine-γ-lyase (47.0 %, p < 0.05), content of H2S in myocardium (by 22.2 %, p<0.05), activity of apoptosis, proliferation and polyploidization in heart, whereas castration of females caused opposite changes in relation to the control group. Gonadectomy in the animals changed the vector of sex differences in the studied parameters: cystathionine-γ-lyase expression and H2S content in myocardium of castrated males was significantly higher, whereas activity of apoptosis, proliferation, and polyploidization were less than in the relevant group of females.

Conclusions. System of cystathionine-γ-lyase/H2S in myocardium is an important molecular target through which multidirectional sex hormones influence on DNA content in the nuclei of myocardial cells of rats is implemented.

References

Regitz-Zagrosek, V., Oertelt-Prigione, S., Seeland, U., & Hetzer, R. (2010). Sex and gender differences in myocardial hypertrophy and heart failure. Circ J, 74(7), 1265–1273. doi: 10.1253/circj.CJ-10-0196.

Ostadal, B., & Ostadal, P. (2014). Sex-based differences in cardiac ischaemic injury and protection: therapeutic implications. Br J Pharmacol, 171(3), 541–554. doi: 10.1111/bph.12270.

Bouma, W., Noma, M., Kanemoto, S., Matsubara, M., Leshnower, B.G, Hinmon, R., et al. (2010). Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression. Am J Physiol Heart Circ Physiol, 298(5), 1510–1517. doi: 10.1152/ajpheart.01021.2009.

Bhupathy, P., Haines, C. D., & Leinwand, L. A. (2010). Influence of sex hormones and phytoestrogens on heart disease in men and women. Womens Health (Lond), 6(1), 77–95. doi: 10.2217/whe.09.80.

Kimura, H. (2014). Production and physiological effects of hydrogen sulfide. Antioxid Redox Signal, 20(5), 783–793. doi: 10.1089/ars.2013.5309.

Calvert, J. W., Coetzee, W. A., & Lefer, D. J. (2010). Novel Insights Into Hydrogen Sulfide–Mediated Cytoprotection. Antioxidants & Redox Signaling, 12(10), 1203–1217. doi: 10.1089/ars.2009.2882.

Papapetropoulos, A., Pyriochou, A., Altaany, Z., Yang, G., Marazioti, A., Zhou, Z., et al. (2009). Hydrogen sulfide is an endogenous stimulator of angiogenesis. Proc Natl Acad Sci U. S. A, 106(51), 21972–21977. doi: 10.1073/pnas.0908047106.

Nomura, T., Ueyama, T., Ashihara, E., Tateishi, K., Asada, S., Nakajima, N., et al. (2008). Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-beta family signaling. Biochem Biophys Res Commun, 365(4), 863–869. doi: 10.1016/j.bbrc.2007.11.087.

Aloisi, A. M., Ceccarelli, I., & Fiorenzani, P. (2003). Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats. Ann. N Y. Acad. Sci., 1007, 232–237. doi: 10.1196/annals.1286.022.

Joshi, S. A., Shaikh, S., Ranpura, S., & Khole, V. V. (2003). Postnatal development and testosterone dependence of a rat epididymal protein identified by neonatal tolerization. Reproduction, 125(4), 3495–3507.

Wiliński, B., Wiliński, J., Somogyi, E., Piotrowska, J., Góralska, M., & Macura, B. (2011). Carvedilol induces endogenous hydrogen sulfide tissue concentration changes in various mouse organs. Folia Biol (Krakow), 59(3–4), 151–155. doi: 10.3409/fb59_3-4.151-155. •

Sen, N., Paul, B. D., Gadalla, M. M., Mustafa, A. K., Sen, T., Xu, R., et al. (2012). Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions. Mol Cell, 45(1), 13–24. doi: 10.1016/j.molcel.2011.10.021.

Varfolomeev, E., Goncharov, T., Vucic, D. (2015). Roles of c-IAP proteins in TNF receptor family activation of NF-κB signaling. Methods Mol Biol, 1280, 269–282. doi: 10.1007/978-1-4939-2422-6_15.

Barr, L. A., & Calvert, J. W. (2014) Discoveries of hydrogen sulfide as a novel cardiovascular therapeutic. Circ J, 78(9), 2111–2118.

Walsh, S., Pontén, A., Fleischmann, B. K., & Jovinge, S. (2010). Cardiomyocyte cell cycle control and growth estimation in vivo--an analysis based on cardiomyocyte nuclei. Cardiovasc Res, 86(3), 365–373. doi: 10.1093/cvr/cvq005.

Zhang, Y., Wang, J., Li, H., Yuan, L., Wang, L., Wu, B., & Ge, J. (2015). Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts. Sci China Life Sci, 58(11), 1126–1134. doi: 10.1007/s11427-015-4904-6.

Meng, G., Zhu, J., Xiao, Y., Huang, Z., Zhang, Y., Tang, X., et al. (2015). Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis. Oxid Med Cell Longev, 2015, 691070. doi: 10.1155/2015/691070.

How to Cite

1.
Melnik AV, Zaichko NV, Chereshnyuk IL, Khodakіvskyi ОА, Haiduk OА. Influence of sex hormones on DNA content and cystathionine-γ-lyase expression in rat myocardium. Zaporozhye Medical Journal [Internet]. 2017Nov.15 [cited 2024Dec.28];(6). Available from: http://zmj.zsmu.edu.ua/article/view/114693

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Section

Original research