Abstract
Microgravity can cause abnormalities and even damage to the cardiovascular system. We investigated if differences exist in the expression level of proteins in myocardial tissues after exposure to simulated microgravity, this could allow to explore microgravity impact on the cardiovascular system. Tail-suspended rats were established as a microgravity model and myocardial tissues were isolated for further identification by 2-dimensional gel electrophoresis (2-DE) combined with mass spectrometry. 864 proteins in myocardial tissues were separated and 15 proteins were identified to be differentially expressed in simulated microgravity model group, including that nine proteins were significantly down-regulated, two were significantly up-regulated, and four barely expressed. The nine down-regulated proteins were further identified as superoxide dismutase (SOD), lactate dehydrogenase (LDH), methylbutenoyl-co-carboxylase, pyruvate kinase 3 or β-fibrinogen, enolase 3, calcineurin (CaN), and two unknown proteins. Particularly, expression of CaN was determined to be down-regulated through Western blotting analysis, which could potentially result in the cardiovascular disorders. Thus, down-regulation of CaN may lead to cardiovascular dysfunction under microgravity. Therefore, improving understanding of the underlying mechanisms of this could provide insights into cardiovascular disorders and potential targets for treatment of cardiovascular diseases under microgravity.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Aubert, A.E., Larina, I., Momken, I., Blanc, S., White, O., Prisk, G.K., Linnarsson, D.: Towards human exploration of space: the THESEUS review series on cardiovascular, respiratory, and renal research priorities. npj Microgravity 2(1), 1–9 (2016)
Christofk, H.R., Vander Heiden, M.G., Wu, N., Asara, J.M., Cantley, L.C.: Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452(7184), 181–186 (2008)
Coghlin, C., Murray, G.I.: Biomarkers of colorectal cancer: recent advances and future challenges. Proteomics Clin. Appl. 9(1–2), 64–71 (2015)
Costa, F., Ambesi-Impiombato, F.S., Beccari, T., Conte, C., Cataldi, S., Curcio, F., Albi, E.: Spaceflight induced disorders: potential nutritional countermeasures. Front. Bioeng. Biotechnol. 9, (2021)
Crucian, B., Sams, C.: Immune system dysregulation during spaceflight: clinical risk for exploration‐class missions. Brain Behav. Immun. 86(5), 1017–1018 (2009)
Falcai, M.J., Louzada, M.J.Q., De Paula, F.J.A., Okubo, R., Volpon, J.B.: A Modified Technique of Rat Tail Suspension for Longer Periods of Observation. Aviat. Space Environ. Med. 83(12), 1176–1180 (2012)
Fan, Q., Li, Y., Gao, J., Mi, T., Shi, H., Zhao, S., Bai, G., Liu, J.: Effects of Taikong Yangxinwan on the Functions of Cardiovascular in Rat under Simulated Weightlessness(in Chinese). Manned Space Flight 19(01), 64–70 (2013)
Ficicioglu, C., Payan, I.: 3-Methylcrotonyl-CoA carboxylase deficiency: metabolic decompensation in a noncompliant child detected through newborn screening. Pediatrics 118(6), 2555–2556 (2006)
Grigoriev, A., Kotovskaya, A., Fomina, G.J.A.A.: The Human Cardiovascular System during Space Flight. 68(9–10), 1495–1500 (2011)
Hodkinson, P., Anderton, R., Posselt, B., Fong, K.J.: An overview of space medicine. Br. J. Anaesth. 119(suppl_1), i143–i153 (2017)
Hughson, R.L., Helm, A., Durante, M.: Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat. Rev. Cardiol. 15(3), 167–180 (2018)
Kowaltowski, A.J., de Souza-Pinto, N.C., Castilho, R.F., Vercesi, A.E.: Mitochondria and reactive oxygen species. Free Radic. Biol. Med. 47(4), 333–343 (2009)
Liu, L., Zhang, D., Li, Y.: LncRNAs in cardiac hypertrophy: from basic science to clinical application. J. Cell Mol. Med. 24(20), 11638–11645 (2020)
Löbrich, M., Jeggo, P.A.J.S.: Hazards of Human Spaceflight. 364(6436), 127–128 (2019)
Molkentin, J.D.: Calcineurin–NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc. Res. 63(3), 467–475 (2004)
Morabito, C., Guarnieri, S., Catizone, A., Schiraldi, C., Ricci, G., Mariggio, M.A.: Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity. Sci. Rep. 7(1), 1–11 (2017)
Mulavara, A.P., Peters, B.T., Miller, C.A., Kofman, I.S., Reschke, M.F., Taylor, L.C., Lawrence, E.L., Wood, S.J., Laurie, S.S., Lee, S.: Physiological and functional alterations after spaceflight and bed rest. Med. Sci. Sports Exerc. 50(9), 1961 (2018)
Park, H.-S., Lee, S.C., Cardenas, M.E., Heitman, J.: Calcium-calmodulin-calcineurin signaling: a globally conserved virulence cascade in eukaryotic microbial pathogens. Cell Host Microbe 26(4), 453–462 (2019)
Parra-Bonilla, G., Alvarez, D.F., Al-Mehdi, A.-B., Alexeyev, M., Stevens, T.: Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation. Am. J. Physiol. Lung Cell Mol. Physiol. 299(4), L513-L522 (2010)
Ranjan, A.K., Gulati, A.: Two-Dimensional Electrophoresis and Mass Spectrometry for Protein Identification, Progenitor Cells. Springer, pp. 185–195 (2019)
Sibonga, J.D.: Spaceflight-induced bone loss: is there an osteoporosis risk? Curr. Osteoporos. Rep. 11(2), 92–98 (2013)
Song, Y., Wang, H., Yue, F., Lv, Q., Cai, B., Dong, N., Wang, Z., Wang, L.: Silk‐Based Biomaterials for Cardiac Tissue Engineering. Adv. Healthc. Mater. 9(23), 2000735 (2020)
Willey, J.S., Britten, R.A., Blaber, E., Tahimic, C.G., Chancellor, J., Mortreux, M., Sanford, L.D., Kubik, A.J., Delp, M.D., Mao, X.W.: The individual and combined effects of spaceflight radiation and microgravity on biologic systems and functional outcomes. J. Environ. Sci. Health C. 39(2), 129–179 (2021)
Zhang, R., Ran, H.H., Cai, L.L., Zhu, L., Sun, J.F., Peng, L., Liu, X.J., Zhang, L.N., Fang, Z., Fan, Y.: Simulated microgravity‐induced mitochondrial dysfunction in rat cerebral arteries. FASEB J. 28(6), 2715–2724 (2014)
Zhao, Y., Zhou, M., Liu, H., Ding, Y., Khong, H., Yu, D., Fodstad, O., Tan, M.J.: Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth. Oncogene 28(42), 3689–3701 (2009)
Zhong, G., Li, Y., Li, H., Sun, W., Cao, D., Li, J., Zhao, D., Song, J., Jin, X., Song, H.J.: Simulated microgravity and recovery-induced remodeling of the left and right ventricle. Front. Physiol. 7, 274 (2016)
Zhu, H., Wang, H., Liu, Z.: Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review. Int. J. Occup. Med. Environ. Health 28(5), 793 (2015)
Funding
This work was supported by State Key Laboratory of Aerospace Medicine Fundamentals and Applications (SMFA12B08); National Natural Science Foundation of China (30772694); International Cooperation Project of the Ministry of Science and Technology of the People’s Republic of China (2006DFA32250).
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Yishu Yin and Junlian Liu designed and performed the majority of the laboratory work. Liguo Guo, Yue Wang and Quanchun Fan helped get animal tissue. Shuang Zhao and Xiaorui Wu assisted in the 2-DE analysis. Yu Liu and Yongzhi Li helped do the data analysis. Weihong Lu and Chong Xu revised the manuscript.
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Yin, Y., Liu, J., Guo, L. et al. Proteomics Identifies Calcineurin as a Potential Target for Cardiovascular Disorders in Rats Exposed to Simulated Microgravity. Microgravity Sci. Technol. 34, 103 (2022). https://doi.org/10.1007/s12217-022-10009-w
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DOI: https://doi.org/10.1007/s12217-022-10009-w