The expression of apoptosis-regulating proteins Bcl-2 and Bad in liver cells of C57Bl/6 mice under light-induced functional pinealectomy and after correction with melatonin
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Abstract
The presence of humans and animals under long-term continuous lighting leads to a suppression of melatonin synthesis, that is, to light-induced functional pinealectomy (LIFP), and the development of desynchronosis. To create LIFP, C57Bl/6 mice were kept under 24-hour lighting (24hL) for 14 days. The animals in the control group were kept under standard lighting conditions. In the next series of experiments, mice with LIFP received daily intragastrically either melatonin (1 mg/kg body weight in 200 μl of distilled water) or 200 μl of water as a placebo. The comparison group consisted of intact animals that received placebo under standard lighting conditions. Immunohistochemical analysis (using an indirect avidin-biotin peroxidase method) revealed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in sinusoid liver cells (a heterogeneous population consisting of the endotheliocytes, Kupffer cells, Ito cells, and Pit cells) and in individual hepatocytes. The Bad expression area in the liver of LIFP mice increased 4 times against a background of the unchanged Bcl-2 expression area. Changes in the brightness (a parameter inversely proportional to the marker concentration) of Bad and Bcl-2 areas did not reach significance. Our results indicate a weakening of the antiapoptotic protection of liver cells of LIFP animals, which creates conditions for activation of the “mitochondrial branch” of apoptosis. Melatonin treatment of LIFP mice resulted in a 3.3-fold increase in Bcl-2 expression area and a 2.7 % decrease in Bcl-2 region brightness compared with the experimental untreated group. Bad protein parameters were unreliable. Thus, melatonin treatment of animals cancels the effect of LIFP, restoring the Bcl-2 expression area and increasing this protein concentration, which indicates an increase in antiapoptotic protection and creates conditions for blocking the development of the “mitochondrial branch” of apoptosis in liver cells.
Supporting agencies: The work was carried out within the framework of the budget project No. 0324-2019-0046. The study was performed using the equipment of the Center for genetic resources of laboratory animals of the Institute of Cytology and Genetics SB RAS, supported by the Ministry of Education and Science of Russia (Unique identifier of the project RFMEFI62119X0023)
About the Authors
S. V. Michurina
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
I. Yu. Ishchenko
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
S. A. Arkhipov
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
A. Yu. Letyagin
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences;
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
M. A. Korolev
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
E. L. Zavjalov
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Novosibirsk
References
1. Agil A., El-Hammadi M., Jiménez-Aranda A., Tassi M., Abdo W., Fernández-Vázquez G., Reiter R.J. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats. J. Pineal. Res. 2015; 59(1):70-79. https://doi.org/10.1111/jpi.12241.
2. Arendt J. Melatonin: countering chaotic time cues. Front. Endocrinol. (Lausanne). 2019;10:391. https://doi.org/10.3389/fendo.2019.00391.
3. Borodin Yu.I., Trufakin V.A., Michurina S.V., Shurlygina A.V. Structural and Temporal Organization of the Liver, Lymphatic, Immune, and Endocrine Systems in Violation of the Light Regime and Melatonin Treatement. Novosibirsk: Manuscript Publ., 2012. (in Russian)
4. ChenW.R., Yang J.Q., Liu F., Shen X.Q., ZhouY.J. Melatonin attenuates vascular calcification by activating autophagy via an AMPK/mTOR/ ULK1 signaling pathway. Exp. Cell. Res. 2020;389(1):111883. https://doi.org/10.1016/j.yexcr.2020.111883.
5. Col C., Dinler K., Hasdemir O., Buyukasik O., Bugdayci G. Oxidative stress and lipid peroxidation products: effect of pinealectomy or exogenous melatonin injections on biomarkers of tissue damage during acute pancreatitis. Hepatobiliary Pancreat. Dis. Int. 2010; 9(1):78-82. PMID: 20133234.
6. Darenskaya M.A., Kolesnikova L.I., Kolesnikov S.I. COVID-19: oxidative stress and the relevance of antioxidant therapy. Vestnik Rossijskoj Akademii Meditsynskikh Nauk = Annals of the Russian Academy of Medical Sciences. 2020;75(4):318-325. https://doi.org/10.15690/vramn1360. (in Russian)
7. Delibas N., Tuzmen N., Yonden Z., Altuntas I. Effect of functional pinealectomy on hippocampal lipid peroxidation, antioxidant enzymes and N-methyl-D-aspartate receptor subunits 2A and 2B in young and old rats. Neuro Endocrinol. Lett. 2002;23(4):345-350. PMID: 12195239.
8. El-Missiry M.A., El-Missiry Z.M.A., Othman A.I. Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19. Eur. J. Pharmacol. 2020;882:173329. https://doi.org/10.1016/j.ejphar.2020.173329.
9. Gupta S., Haldar C. Nycthemeral variation in melatonin receptor expression in the lymphoid organs of a tropical seasonal breeder Funambulus pennanti. J. Comp. Physiol. A. 2014;200(12):1045-1055. https://doi.org/10.1007/s00359-014-0959-2.
10. Hardeland R. Melatonin and the electron transport chain. Cell. Mol. Life Sci. 2017;74(21):3883-3896. https://doi.org/10.1007/s00018-017-2615-9.
11. Hu J., Srivastava K., Wieland M., Runge A., Mogler C., Besemfelder E., Terhardt D., Vogel M.J., Cao L., Korn C., Bartels S., Thomas M., Augustin H.G. Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat. Science. 2014; 343(6169):416-419. https://doi.org/10.1126/science.1244880.
12. Huo X., Wang C., Yu Z., Peng Y., Wang S., Feng S., Zhang S., Tian X., Sun C., Liu K., Deng S., Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: an implication of the therapeutic potential. J. Pineal Res. 2017;62(4): e12390. https://doi.org/10.1111/jpi.12390.
13. Ishchenko I.Y., Michurina S.V. Regional lymph nodes in the liver of rats in functional pinealectomy. Bull. Exp. Biol. Med. 2014;157(5): 671-676. https://doi.org/10.1007/s10517-014-2636-4.
14. Jing Y., Bai F., Chen H., Dong H. Melatonin prevents blood vessel loss and neurological impairment induced by spinal cord injury in rats. J. Spinal. Cord. Med. 2017;40(2):222-229. https://doi.org/10.1080/10790268.2016.1227912.
15. Jockers R., Delagrange P., Dubocovich M.L., Markus R.P., Renault N., Tosini G., Cecon E., Zlotos D.P. Update on melatonin receptors: IUPHAR Review 20. Br. J. Pharmacol. 2016;173(18):2702-2725. https://doi.org/10.1111/bph.13536.
16. Jou M.J., Peng T.I., Reiter R.J. Protective stabilization of mitochondrial permeability transition and mitochondrial oxidation during mitochondrial Ca2+ stress by melatonin’s cascade metabolites C3-OHM and AFMK in RBA1 astrocytes. J. Pineal Res. 2019;66(1):e12538. https://doi.org/10.1111/jpi.12538.
17. Li R., Toan S., Zhou H. Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease. Aging (Albany NY). 2020;12(7):6467-6485. https://doi.org/10.18632/aging.102972.
18. Michurina S.V., Ishchenko I.Yu., Arkhipov S.A., Cherepanova M.A., Vasendin D.V., Zavjalov E.L. Apoptosis in the liver of male db/db mice during the development of obesity and type 2 diabetes. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2020;24(4):435-440. https://doi.org/10.18699/VJ20.43-o.
19. Michurina S.V., Ischenko I.Yu., Arkhipov S.A., Klimontov V.V., Cherepanova M.A., Korolev M.A., Rachkovskaya L.N., Zav’yalov E.L., Konenkov V.I. Melatonin-aluminum oxide-polymethylsiloxane complex on apoptosis of liver cells in a model of obesity and type 2 diabetes mellitus. Bull. Exp. Biol. Med. 2017;164(2):165-169. https://doi.org/10.1007/s10517-017-3949-x.
20. Michurina S.V., Ishchenko I.Yu., Arkhipov S.A., Klimontov V.V., Rachkovskaya L.N., Konenkov V.I., Zavyalov E.L. Effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 in the liver of mice with obesity and type 2 diabetes mellitus. Bull. Exp. Biol. Med. 2016;162(2):269-272. https://doi.org/10.1007/s10517-016-3592-y.
21. Michurina S.V., Shurlygina A.V., Belkin A.D., Vakulin G.M., Verbitskaia L.V., Trufakin V.A. Changes in liver and in some organs of immune system of animals exposed to twenty-four-hour illumination. Morfologiia. 2005;128(4):65-68. PMID: 16400925. (in Russian)
22. Michurina S.V., Vasendin D.V., Ishchenko I.Yu. Physiological and biological effects of melatonin: some results and prospects for the study. Rossiyskiy Fiziologicheskiy Zhurnal im. I.M. Sechenova = I.M. Sechenov Physiological Journal. 2018;104(3):257-271. (in Russian)
23. Morin L.P. Nocturnal light and nocturnal rodents: similar regulation of disparate functions? J. Biol. Rhythms. 2013;28(2):95-106. https://doi.org/10.1177/0748730413481921.
24. Motoyama S., Saito S., Alojado M.E., Itoh H., Kitamura M., Suzuki H., Saito R., Momiyama H., Nakae H., Ogawa J., Inaba H. Hydrogen peroxide induces midzonal heat shock protein 72 and apoptosis in sinusoidal endothelial cells of hypoxic rat liver. Crit. Care Med. 2000; 28(5):1509-1514. https://doi.org/10.1097/00003246-200005000-00042.
25. Motoyama S., Saito S., Saito R., Minamiya Y., Nakamura M., Okuyama M., Imano H., Ogawa J. Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver. J. Surg. Res. 2003; 110(1):211-216. https://doi.org/10.1016/s0022-4804(03)00006-4.
26. Polčic P., Mentel M. Reconstituting the mammalian apoptotic switch in yeast. Genes (Basel ). 2020;11(2):145. https://doi.org/10.3390/genes11020145.
27. Reiter R.J., Rosales-Corral S.A., Tan D.X., Alatorre-Jimenez M., Lopez C. Circadian dysregulation and melatonin rhythm suppression in the context of aging. In: Jazwinski S., Belancio V., Hill S. (Eds). Circadian Rhythms and Their Impact on Aging. (Ser. Healthy Ageing and Longevity. Vol. 7). Springer, Cham, 2017;1-25. https://doi.org/10.1007/978-3-319-64543-8_1.
28. Reiter R.J., Tan D.X., Rosales-Corral S., Galano A., Jou M.J., AcunaCastroviejo D. Melatonin mitigates mitochondrial meltdown: interactions with SIRT3. Int. J. Mol. Sci. 2018;19(8):2439. https://doi.org/10.3390/ijms19082439.
29. Reiter R.J., Tan D.X., Rosales-Corral S., Manchester L.C. The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini-Rev. Med. Chem. 2013;13(3):373-384. https://doi.org/10.2174/1389557511313030006.
30. Russart K.L.G., Nelson R.J. Light at night as an environmental endocrine disruptor. Physiol. Behav. 2018;190:82-89. https://doi.org/10.1016/j.physbeh.2017.08.029.
31. Sahna E., Parlakpinar H., Vardi N., Ciğremis Y., Acet A. Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats. Acta Histochem. 2004;106(5):331-336. https://doi.org/10.1016/j.acthis.2004.07.006.
32. Willis S., Day C.L., Hinds M.G., Huang D.C. The Bcl-2-regulated apoptotic pathway. J. Cell. Sci. 2003;116(Pt.20):4053-4056. https://doi.org/10.1242/jcs.00754.
33. Woolbright B.L., Jaeschke H. Xenobiotic and endobiotic mediated interactions between the cytochrome P450 system and the inflammatory response in the liver. Adv. Pharmacol. 2015;74:131-161. https://doi.org/10.1016/bs.apha.2015.04.001.
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