Hypercapnia-inducible factor: a hypothesis
Abstract
Abstract. Cells and tissues sense and respond to hypercapnia by global activation or down-regulation of hundreds of genes and switching on/off a number of signaling and metabolic pathways. We hypothesize for the first time that such complex rearrangements are hardly possible without subtle guidance by a specific master regulator which we suggest to name hypercapnia-inducible factor (HcIF). Whether there are structural and functional similarities between HcIF and HIF remain to be elucidated. However, there are reasons to believe that, as master genes, HcIF and HIF can cooperate or compete depending on the situation. Only further research will warrant existence of HcIF as a molecular master regulator of the response to hypercapnia.
References
Taylor, C. T.; Cummins, E. P. Regulation of gene expression by carbon dioxide. J Physiol 2011, 589, 4, 797-803. doi: 10.1113/jphysiol.2010.201467
Schmidt, H.; Malik, A.; Bicker, A.; Poetzsch, G.; Avivi, A. et al. Hypoxia tolerance, longevity and cancer-resistance in the mole rat Spalax – a liver transcriptomics approach. Sci Rep 2017, 7, 1, p. 14348. doi: 10.1038/s41598-017-13905-z
Shigemura, M.; Lecuona, E.; Angulo, M.; Dada, L. A.; Edwards, M. B. et al. Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans. Sci Rep 2019, 9, 1, p. 18251. doi: 10.1038/s41598-019-54683-0.
Shigemura, M.; Welch, L. C.; Sznajder, J. I. Hypercapnia regulates gene expression and tissue function. Front Physiol 2020; 598111-598122. doi:10.3389/fphys.2020.598122.
Cummins, E. P.; Strowitzki, M. J.; Taylor, C. T. Mechanisms and consequences of oxygen and carbon dioxide sensing in mammals. Physiol Rev 2020, 100, 1, 463-488. doi: 10.1152/physrev.00003.2019
Muradian, K. K.; Tolstun, D. A.; Paier, A. G.; Popa-Wagner, A.; Fraifeld, V. E. Embryonic stem cells, telomeres and aging. J Ageing Restor Med 2019, 2, 3, 115-122.
Planavsky, N. J.; Reinhard, C. T.; Wang, X.; Thomson, D.; McGoldrick, P. et al. Earth history. Low mid-Proterozoic atmospheric oxygen levels and the delayed rise of animals. Science 2014; p. 346, 635-638. doi: 10.1126/science.1258410
Wong, M. L.; Charnay, B. D.; Gao, P., Yung, Y. L.; Russell, M. J. Nitrogen Oxides in Early Earth's Atmosphere as Electron Acceptors for Life's Emergence. Astrobiology 2017, 10, 975-983. doi: 10.1089/ast.2016.1473. Epub 2017 Oct 12. PMID: 29023147
Catling, D. C,; Zahnle, K. J. The Archean atmosphere. Sci Adv 2020; 6, 9, eaax1420. doi: 10.1126/sciadv.aax1420
Wang, G. L.; Jiang, B. H; Rue, E. A.; Semenza, G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 1995, 92, 12, 5510-5514.
Semenza, G. L. Hypoxia-inducible factors in physiology and medicine. Cell 2012, 148, 3, 399-408. doi: 10.1016/j.cell.2012.01.021
Jiang, B. H.; Rue, E.; Wang, G. L.; Roe, R.; Semenza, G. L. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 1996, 271, 30, 17771-17778
Pagani, A.; Aitzetmüller, M. M.; Brett, E. A.; König, V.; Wenny, R. et al. Skin Rejuvenation through HIF-1α Modulation. Plast Reconstr Surg 2018, 141, 4, 600e-607e. doi: 10.1097/PRS.0000000000004256
Saha, P.; Kim, M.; Tulshyan, A.; Guo, Y.; Mishra, R. et al. Hypoxia-inducible factor 1-alpha enhances the secretome to rejuvenate adult cardiosphere-derived cells. J Thorac Cardiovasc Surg 2021, S0022-5223, 21, 01046-1. doi: 10.1016/j.jtcvs.2021.07.015
Tyshkovskiy, A.; Bozaykut, P.; Borodinova, A. A.; Gerashchenko, M. V.; Ables, G. P. et al. Identification and application of gene expression signatures associated with lifespan extension. Cell Metab 2019, 30, 3, 573-593.e8. doi: 10.1016/j.cmet.2019.06.018
Sharabi, K.; Hurwitz, A.; Simon, A. J.; Beitel, G. J.; Morimoto, R. I. et al. Elevated CO2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans. Proc Natl Acad Sci U S A 2009, 106, 10, 4024-4029. doi: 10.1073/pnas.0900309106
Zuela, N.; Friedman, N.; Zaslaver, A.; Gruenbaum,Y. Measuring the effects of high CO2 levels in Caenorhabditis elegans. Methods 2014, 68, 3, 487-491. doi: 10.1016/j.ymeth.2014.03.008
Timchenko, A. N.; Utko, N. A.; Muradian, K. H. The higher oxygen content in the atmosphere decreases and carbon dioxide increases the lifespan of Drosophila melanogaster (in Russian). Problems of Aging and Longevity 2008, 17, 2, 230–239.
Timchenko, A. N.; Tolstun, D. A.; Bezrukov, V. V.; Muradian, K. K. Hypercapnic atmosphere as a means of reducing the oxidative processes, preventing excess metabolism and life extension (in Russian). Problems of Aging and Longevity 2012, 21, 43–44.
Selfridge, A. C.; Cavadas, M. A.; Scholz, C. C.; Campbell, E. L.; Welch, L. C. et al. Hypercapnia suppresses the HIF-dependent adaptive response to hypoxia. J Biol Chem 2016, 291, 22, 11800-11808.
Tsuji, T.; Aoshiba, K.; Itoh, M.; Nakamura, H.; Yamaguchi, K. Hypercapnia accelerates wound healing in endothelial cell monolayers exposed to hypoxia. Open Respir Med J 2013, 7, 6-12. doi: 10.2174/1874306401307010006
Tolstun, D.; Knyazer, A.; Tushynska, T.; Dubiley, T.; Bezrukov, V. et al. Metabolic remodeling of mice by hypoxic-hypercapnic environment: imitating the naked mole-rat. Biogerontology 2020, 21, 143-153. doi: 10.1007/s10522-019-09848-9
Chi, Y. H.; Ahn, J. E.; Yun, D. J.; Lee, S. Y.; Liu, T. X. et al. Changes in oxygen and carbon dioxide environment alter gene expression of cowpea bruchids. J Insect Physiol 2011, 57, 1, 220-230. doi: 10.1016/j.jinsphys.2010.11.011