Bansal, S.; Li, Y.; Bansal, S.; Klotzbier, W.; Singh, B.; Jayatilake, M.; Sridharan, V.; Fernández, J.A.; Griffin, J.H.; Weiler, H.; Boerma, M.; Cheema, A.K. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma. Metabolites2024, 14, 245.
Bansal, S.; Li, Y.; Bansal, S.; Klotzbier, W.; Singh, B.; Jayatilake, M.; Sridharan, V.; Fernández, J.A.; Griffin, J.H.; Weiler, H.; Boerma, M.; Cheema, A.K. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma. Metabolites 2024, 14, 245.
Bansal, S.; Li, Y.; Bansal, S.; Klotzbier, W.; Singh, B.; Jayatilake, M.; Sridharan, V.; Fernández, J.A.; Griffin, J.H.; Weiler, H.; Boerma, M.; Cheema, A.K. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma. Metabolites2024, 14, 245.
Bansal, S.; Li, Y.; Bansal, S.; Klotzbier, W.; Singh, B.; Jayatilake, M.; Sridharan, V.; Fernández, J.A.; Griffin, J.H.; Weiler, H.; Boerma, M.; Cheema, A.K. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma. Metabolites 2024, 14, 245.
Abstract
Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems including kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind-legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TCA and urea cycles, and arginine metabolism. We also observed gender and genotype modulated metabolic perturbations post radiation exposure. The APCHi mice showed near normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites including amino acids, citric acid, and hypoxanthine in APCHi mice are indicative of APC-mediated protection from radiation injuries. With the help of these findings the role of APC in plasma molecular events after acute -radiation exposure in a gender-specific manner can be established for the first time.
Keywords
Activated Protein C; Metabolomics; Lipidomics; DEARE; Radiation injury; C57BL/6N mouse
Subject
Biology and Life Sciences, Other
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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