Transcriptomic and Metabolomic Differential Responses in Hypoxia on RBL-2H3 Cell Through Sodium Cromoglycate Mediates
DOI:
https://doi.org/10.21070/ijhsm.v1i2.17Keywords:
Hypoxia, Transcriptome, Metabolomics, RBL-2H3 cellsAbstract
Hypoxia is a state in which sufficient oxygen is not available at the tissue level, a condition that leads to hypoxemia. Mast cells (MCs) are tissue resident cells that are widely distributed in vascularized tissues such as airways and gastrointestinal tract. Previously, studies have established the effect of pre-treatment of MCs with Sodium Cromoglicate (SCG) inhibitor in lung tissues of SD rats. Thus, due to the complexity and less understanding of the cell structure of lung tissues, and in order to understand the changes of MCs under hypoxia, RBL-2H3 were utilized in an experimental in-vitro study that aimed to evaluate the transcriptomic and metabolomic variations of these cells under hypoxic conditions and after pre-treatment with SCG. Differential expression analysis identified 25 genes as differentially expressed between HSCG vs HC group. On KEGG pathway enrichment analysis, Arachidonic acid metabolism, glutathione metabolism and AMPK pathway were among the enriched pathways in the HSCG vs HC group. A total of 1,513 metabolites were identified. These metabolites were amino acids, fatty acids, organic acids, lipids, carbohydrates, and others. Metabolic pathway enrichment analysis revealed that in the HSCG_vs_HC group, Glutathione, Val-Val, Arg-Glu, Pro-Glu and 1-Stearoyl-rac-glycerol were upregulated whereas, Cytidine, Hypoxanthine, Histamine and Pro-Asp were decreased. In conclusion, our study findings reveal that SCG impacts on cell mechanisms under hypoxic conditions.
References
2. C. C. Cai et al., "Glycine protects against hypoxic-ischemic brain injury by regulating mitochondria-mediated autophagy via the AMPK pathway," Oxidative Medicine and Cellular Longevity, vol. 2019, pp. 1–12, 2019. doi: 10.1155/2019/4248529.
3. R. Cavill, D. Jennen, J. Kleinjans, and J. J. Briedé, "Transcriptomic and metabolomic data integration," Briefings in Bioinformatics, vol. 17, no. 5, pp. 891–901, 2016. doi: 10.1093/bib/bbv090.
4. W. C. Chang, "Store-operated calcium channels and pro-inflammatory signals," Acta Pharmacologica Sinica, vol. 27, no. 7, pp. 791–796, 2006. doi: 10.1111/j.1745-7254.2006.00395.x.
5. A. Dalla Valle et al., "Induction of Stearoyl-CoA 9-Desaturase 1 protects human mesenchymal stromal cells against palmitic acid-induced lipotoxicity and inflammation," Frontiers in Endocrinology, vol. 10, p. 726, 2019. doi: 10.3389/fendo.2019.00726.
6. F. Dengler, "Activation of AMPK under hypoxia: Many roads leading to Rome," International Journal of Molecular Sciences, vol. 21, no. 7, pp. 1–26, 2020. doi: 10.3390/ijms21072428.
7. F. Dengler and G. Gäbel, "The fast lane of hypoxic adaptation: Glucose transport is modulated via a HIF-hydroxylase-AMPK-axis in jejunum epithelium," International Journal of Molecular Sciences, vol. 20, no. 20, pp. 1–19, 2019. doi: 10.3390/ijms20204993.
8. F. Dengler, R. Rackwitz, H. Pfannkuche, and G. Gäbel, "Glucose transport across lagomorph jejunum epithelium is modulated by AMP-activated protein kinase under hypoxia," Journal of Applied Physiology, vol. 123, no. 6, pp. 1487–1500, 2017. doi: 10.1152/japplphysiol.00436.2017.
9. K. J. Dunham-Snary et al., "Hypoxic pulmonary vasoconstriction: From molecular mechanisms to medicine," Chest, vol. 151, no. 4, pp. 940–951, 2017. doi: 10.1016/j.chest.2016.09.001.
10. A. M. Edwards and J. B. L. Howell, "The chromones: History, chemistry, and clinical development," Clinical and Experimental Allergy, vol. 30, no. 5, pp. 756–764, 2000. doi: 10.1046/j.1365-2222.2000.00879.x.
11. F. H. Falcone, D. Wan, N. Barwary, and R. Sagi-Eisenberg, "RBL cells as models for in vitro studies of mast cells and basophils," Immunological Reviews, vol. 282, no. 1, pp. 63–79, 2018. doi: 10.1111/imr.12628.
12. M. T. Flowers and J. M. Ntambi, "Role of stearoyl-CoA desaturase in regulating lipid metabolism," Current Opinion in Lipidology, vol. 19, no. 3, pp. 248–256, 2008. doi: 10.1097/MOL.0b013e3282f9b54d.
13. M. Gaczynska, P. A. Osmulski, Y. Gao, M. J. Post, and M. Simons, "Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity," Biochemistry, vol. 42, no. 29, pp. 8663–8670, 2003. doi: 10.1021/bi034784f.
14. S. J. Galli et al., "Mast cells as 'tunable' effector and immunoregulatory cells: Recent advances," Annual Review of Immunology, vol. 23, pp. 749–786, 2005. doi: 10.1146/annurev.immunol.21.120601.141025.
15. C. Gu and J. C. Jun, "Does hypoxia decrease the metabolic rate?" Frontiers in Endocrinology, vol. 9, p. 668, 2018. doi: 10.3389/fendo.2018.00668.
16. G. A. Gusarova et al., "Hypoxia leads to Na,K-ATPase downregulation via Ca2+ release-activated Ca2+ channels and AMPK activation," Molecular and Cellular Biology, vol. 31, no. 17, pp. 3546–3556, 2011. doi: 10.1128/mcb.05114-11.
17. C. A. Hales and H. Kazemi, "Role of histamine in the hypoxic vascular response of the lung," Respiration Physiology, vol. 24, no. 1, pp. 81–88, 1975. doi: 10.1016/0034-5687(75)90123-1.
18. J. Q. Han, K. Y. Yu, and M. He, "Effects of puerarin on the neurocyte apoptosis and p-Akt (Ser473) expressions in rats with cerebral ischemia/reperfusion injury," Chinese Journal of Integrated Traditional and Western Medicine, vol. 32, no. 8, pp. 1069–1072, 2012.
19. T. Hashimoto et al., "Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their activities through Src and AMPK signaling pathways," Biochemical and Biophysical Research Communications, vol. 505, no. 1, pp. 13–19, 2018. doi: 10.1016/j.bbrc.2018.09.068.
20. H. Hu et al., "The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway," Biomedicine and Pharmacotherapy, vol. 117, p. 109106, 2019. doi: 10.1016/j.biopha.2019.109106.
21. W. W. Hu and Z. Chen, "Role of histamine and its receptors in cerebral ischemia," ACS Chemical Neuroscience, vol. 3, no. 4, pp. 302–311, 2012. doi: 10.1021/cn200126p.
22. Y. Hu and W. M. Kuebler, "The role of mast cells in pulmonary hypertension," Journal of Rare Diseases Research & Treatment, vol. 2, pp. 1–10, 2017.
