Experimental study of the pattern of genes activated by multi-day intermittent hypoxia in the rat pancreas

Authors

DOI:

https://doi.org/10.14739/2310-1237.2023.3.292536

Keywords:

pancreas, hypoxia, Cops5, F10, Jmjd6, Lgals3, Rbpjl, Vegfa genes

Abstract

Intermittent hypoxia affects a variety of pathological conditions in the body and is used in medicine to reproduce the sanogenic therapeutic effect. Intermittent hypoxia is used for clinical indications to improve lung function; increase the body’s adaptive capacity; in obstructive sleep apnoea syndrome; in anaemia, diabetes mellitus. In cancer radiotherapy, intermittent hypoxic training helps to increase the sensitivity of the tumour to treatment. Intermittent hypoxia is useful in rehabilitation medicine to improve the physical recovery of patients after surgery or injury to improve the body’s functional capabilities. However, to date, the activity of regulatory genes, that activate the molecular mechanisms of the above-mentioned sanogenic effects of intermittent hypoxia has not been sufficiently studied.

The aim of the study: to determine the expression of hypoxia-related genes in pancreas of Wistar rats under intermittent hypoxia.

Materials and methods. The CFX-96 Touch™ real-time reverse transcription polymerase chain reaction (PCR) (Bio-Rad, USA) and the RT2 Profiler™ PCR Array Rat Hypoxia Signalling Pathway kit (QIAGEN, Germany) were used to analyse gene expression in experimental animals, where 84 genes involved in the hypoxia signalling pathway identified in the pancreas were studied.

Results. According to the results of PCR analysis of pancreatic samples from intact animals and animals exposed to hypoxic training, the activity of the gene panel can be distributed as follows: genes with high expression compared to the intact group of animals, genes with low expression compared to the intact group of animals and genes in which no significant changes were detected in the samples compared to the intact group of animals. We have found, that the genes Cops5, F10, Jmjd6, Lgals3, Rbpjl, Vegfa have high expression activity compared to the intact group of animals.

Conclusions. The increase in the expression of Cops5 by 10.29 times, Lgals3 by 2.94 times and Rbpjl by 5.73 times as a result of intermittent hypoxia can be regarded as an activating factor for the increase in the proliferation of endocrine and exocrine pancreatic cells and the growth of their antiapoptotic potential. The 3.20-fold increase in Jmjd6 gene expression under intermittent hypoxia can be interpreted as a regulatory effect through protein dehydroxylation and promotion of antiapoptotic protein activity in endocrine and exocrine pancreatic cells. The 5.99-fold increased level of Vegfa expression may promote angiogenesis in the pancreas under intermittent hypoxia.

Author Biographies

T. V. Ivanenko, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, Associate Professor of the Department of Pathological Physiology with Course of Normal Physiology

Yu. M. Kolesnyk, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, DSc, Professor of the Department of Pathological Physiology with the Course of Normal Physiology, Rector of Zaporizhzhia State Medical and Pharmaceutical University, Honored Science and Technology Figure of Ukraine

A. V. Abramov, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, DSc, Professor of the Department of Pathological Physiology with the Course of Normal Physiology

References

Navarrete-Opazo, A., & Mitchell, G. S. (2014). Therapeutic potential of intermittent hypoxia: a matter of dose. American journal of physiology. Regulatory, integrative and comparative physiology, 307(10), R1181-R1197. https://doi.org/10.1152/ajpregu.00208.2014

Raffay, T. M., & Martin, R. J. (2020). Intermittent hypoxia and bronchial hyperreactivity. Seminars in fetal & neonatal medicine, 25(2), 101073. https://doi.org/10.1016/j.siny.2019.101073

Korkushko, O. V., & Slipchenko, V. H. (Eds.). (2015). Hipoksiia yak metod pidvyshchennia adaptatsiinoi zdatnosti orhanizmu [Hypoxia as a method of increasing the adaptive capacity of the body]. Kyiv: NTUU "KPI". [in Ukrainian].

Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021). Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target. International journal of molecular sciences, 22(11), 5703. https://doi.org/10.3390/ijms22115703

Gonzalez-Rothi, E. J., Lee, K. Z., Dale, E. A., Reier, P. J., Mitchell, G. S., & Fuller, D. D. (2015). Intermittent hypoxia and neurorehabilitation. Journal of applied physiology, 119(12), 1455-1465. https://doi.org/10.1152/japplphysiol.00235.2015

Ivanenko, T. V, Kolesnyk, Yu. M, & Abramova, T. V. (2017). Analiz endokrynnoho statusu ta rivnia ekspresii bilkiv apoptozu i proliferatsii v pankreatychnykh ostrivtsiakh shchuriv z eksperymentalnym tsukrovym diabetom pislia zakinchennia pereryvchastykh hipoksychnykh trenuvan. Patolohiia, reabilitatsiia, adaptatsiia, 15(2), 17-20. [in Ukrainian].

Ivanenko, T. V. (2015). Vliyanie gipoksicheskikh trenirovok na tsitoarkhitektoniku pankreaticheskikh ostrovkov pri eksperimentalnom sakharnom diabete. Pathologia, (1 Suppl), 52-53. [in Russian].

Ivanenko, T. V., Abramov, A. V., Kolesnyk, Yu. M., Zhulinskyi, V. O., & Kovalov, M. M. (2013). Stymuliatsiia funktsionalnoho stanu beta-klityn pankreatychnykh ostrivtsiv bahatodennoiu pereryvchastoiu hipoksiieiu. Zdobutky klinichnoi i eksperymentalnoi medytsyny, (2), 246. [in Ukrainian].

Ivanenko, T. V., & Vynokurova, A. V. (2021). Kliuchovi molekuliarno-henetychni rehuliatory dyferentsiiuvannia endokrynotsytiv pidshlunkovoi zalozy [Key molecular genetic regulators of pancreatic endocrinocyte differentiation]. Klinichna ta eksperymentalna patolohia, 20(4), 116-121. [in Ukrainian]. https://doi.org/10.24061/1727-4338.XX.4.78.2021.15

Rukstalis, J. M., & Habener, J. F. (2009). Neurogenin3: a master regulator of pancreatic islet differentiation and regeneration. Islets, 1(3), 177-184. https://doi.org/10.4161/isl.1.3.9877

Nimker, C., Singh, D. P., Saraswat, D., & Bansal, A. (2016). Preconditioning with ethyl 3,4-dihydroxybenzoate augments aerobic respiration in rat skeletal muscle. Hypoxia, 4, 109-120. https://doi.org/10.2147/HP.S102943

Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262

Mo, C., Xu, M., Wen, C., Chang, R., Huang, C., Zou, W., Zhu, X., & Guo, Q. (2018). Normalizing JMJD6 Expression in Rat Spinal Dorsal Horn Alleviates Hyperalgesia Following Chronic Constriction Injury. Frontiers in neuroscience, 12, 542. https://doi.org/10.3389/fnins.2018.00542

Xu, G., Chen, H., Wu, S., Chen, J., Zhang, S., Shao, G., Sun, L., Mu, Y., Liu, K., Pan, Q., Li, N., An, X., Lin, S., & Chen, W. (2022). Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance. Cell death & disease, 13(8), 683. https://doi.org/10.1038/s41419-022-05033-y

Pan, L., Hoffmeister, P., Turkiewicz, A., Huynh, N. N. D., Große-Berkenbusch, A., Knippschild, U., Gebhardt, J. C. M., Baumann, B., Borggrefe, T., & Oswald, F. (2021). Transcription Factor RBPJL Is Able to Repress Notch Target Gene Expression but Is Non-Responsive to Notch Activation. Cancers, 13(19), 5027. https://doi.org/10.3390/cancers13195027

Wong, W. P. S., Wang, J. C., Schipma, M. J., Zhang, X., Edwards, J. R., & El Muayed, M. (2021). Cadmium-mediated pancreatic islet transcriptome changes in mice and cultured mouse islets. Toxicology and applied pharmacology, 433, 115756. https://doi.org/10.1016/j.taap.2021.115756

Kolesnik, Yu. M., Abramov, A. V., Ivanenko, T. V., Zhulinskii, V. A., & Gancheva, O. V. (2012). Sanogennoe vliyanie mnogodnevnykh gipoksicheskikh trenirovok na endokrinnuyu funktsiyu pankreaticheskikh ostrovkov krys s eksperimentalnym sakharnym diabetom. Fiziolohichnyi zhurnal, 58(4), 67. [in Russian].

White, A. L., & Bix, G. J. (2023). VEGFA Isoforms as Pro-Angiogenic Therapeutics for Cerebrovascular Diseases. Biomolecules, 13(4), 702. https://doi.org/10.3390/biom13040702

Ivanenko, T. V., Abramov, A. V., Kolesnik, Yu. M., & Vasilenko, G. V. (2011). Endokrinnyi status i uroven ekspressii belkov Bcl-2 i p53 v pankreaticheskikh ostrovkakh u krys s eksperimentalnym sakharnym diabetom [Endocrine status and the level of Bcl2 and p53 protein expression in pancreatic islets of rats with experimental diabetes mellitus]. Pathologia, 8(2), 18-20. [in Russian].

Published

2023-12-22

How to Cite

1.
Ivanenko TV, Kolesnyk YM, Abramov AV. Experimental study of the pattern of genes activated by multi-day intermittent hypoxia in the rat pancreas. Pathologia [Internet]. 2023Dec.22 [cited 2024Mar.2];20(3):218-21. Available from: http://pat.zsmu.edu.ua/article/view/292536

Issue

Section

Original research