title: Revisiting cobalt chloride preconditioning to prevent hypobaric hypoxia-induced damage: identification of global proteomic alteration and key networks.
abstract: Several studies have supported the hypoxia mimetic roles and cytoprotective properties of cobalt chloride in vitro and in vivo. However, a clear understanding of biological process-based mechanism that integrates the available information remains unknown. This study was aimed to explore the potential mechanism of cobalt chloride deciphering its benefits and well-known physiological challenge caused by hypobaric hypoxia that reportedly affects nearly 24 % of the global population. In order to explore the mechanism of CoCl2, we used global proteomic and systems biology approach in rat model to provide a deeper insight into molecular mechanisms of preconditioning. Furthermore, key conclusions were drawn based on biological network analysis and their enrichment with ontological overlaps. The study was further strengthened by consistent identification of validation of proteins using immunoblotting. CoCl2-pretreated animals exposed to hypoxia showed two significant networks, one lipid metabolism and other cell cycle associated, with a total score of 23 and eight focus molecules. In this study, we delineated two primary routes: one, by direct modulation of reactive oxygen species metabolism and, second, by regulation of lipid metabolism which was not known until now. The previously known benefits of cobalt chloride during physiological challenge by hypobaric hypoxia are convincing and could be explained by some basic set of metabolic and molecular reorganization within the hypoxia model. Interestingly, we also observed some of the completely unknown roles of cobalt chloride such as regulation of lipid that could undulate the translational roles of cobalt chloride supplementation beyond hypoxia preconditioning.
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India. yasminchem@gmail.com.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Ahmad
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Adtiya
authors.initials: A
authors.lastname: Arya
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Subhojit
authors.initials: S
authors.lastname: Paul
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Neurobiology Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Prasad
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Lucknow Road Timarpur, Delhi, 110054, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Bhargava
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D003035:Cobalt / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control; D050356:Lipid Metabolism / Q000235:genetics*; D040901:Proteomics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003035:Cobalt; C018021:cobaltous chloride
keywords: Biological networks; Cobalt chloride preconditioning; Hypobaric hypoxia; Proteomics