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.

The meta‐analytical paradigm in an in silico hybrid: Pathways and networks perturbed during exposure to varying degrees of hypobaric hypoxia

“…This study, for the first time, reveals the universally perturbed pathways in both rat and human unhindered by differing conditions of hypoxic exposure. The collective studies (as shown in Supporting Information Data File S1) provide proteomic investigations of the plasma or specific tissues where subject was either human or rat . Some studies showcase only DE proteins but stop short of providing information regarding the processes that these proteins will affect.…”

“…The datasets taken were from the authors’ previous publications regarding effects of HH on proteome and a few other select publications regarding the same [, ] for a total of 154 DE proteins. The datasets were chosen on the basis of two criteria.…”

“…Hypobaric hypoxia (HH) is a decline in the oxygen reserves of an organism due to decreasing barometric pressure that causes a remarkable perturbation in complex III of the electron transport chain. The secondary effects of HH on proteomes are reported in numerous publications . These studies constrained HH to particular organism for fixed duration and intensity.…”

“…Therefore, a protein list comprising 154 differentially expressed (DE) proteins was created using previous studies [, ] that investigated the proteome of either human or Sprague–Dawley rat or both to find the pathways and networks perturbed by HH. The conjoining of two disparate organisms across genera and species stems from the authors’ past studies wherein it was clearly demonstrated that both the model organism (Sprague–Dawley rat) and the actual organism (human) have similar responses to HH at the physiological and proteome levels .…”

Cobalt in athletes: hypoxia and doping - new crossroads

“…Generation of Co-substituted myoglobin is used in designing artificial myoglobin-based oxygen carriers (Neya et al, 2014). In addition, cobalt preconditioning also affects other key networks, including lipid metabolism and cell cycle regulation (Ahmad et al, 2016).…”