Abstract
General anaesthesia is associated with hypothermia, oxidative stress, and immune depression. Uncoupling Protein (UCP2) is a member of the mitochondrial carrier family present in many organs including the spleen, the lung and the brain. A role of UCP2 in the activation of the inflammatory/immune cells, in the secretion of hormones, and in the excitability of neurons by regulating the production of reactive oxygen species has been discussed. Because of the side effects of anaesthesia listed above, we aimed to question the expression and the function of UCP2 during anaesthesia. Induction of anaesthesia with ketamine (20 mg/kg) or isoflurane (3.6%) and induction of sedation with the α2 adrenergic receptor agonist medetomidine (0.2 mg/kg) stimulated infiltration of immune cells in the lung and increased UCP2 protein content in the lung, in both immune and non-immune cells. UCP2 content in the lung inversely correlated with body temperature decrease induced by medetomidine treatment. Challenge of the Ucp2−/− mice with isoflurane and medetomidine revealed an earlier behavioral recovery phenotype. Transponder analysis of body temperature and activity showed no difference between Ucp2−/− and control mice in basal conditions. However, upon an acute decrease of body temperature induced by medetomidine, Ucp2−/− mice exhibited increased locomotion activity. Together, these results show that UCP2 is rapidly mobilized during anaesthesia and sedation in immune cells, and suggest a role of UCP2 in locomotion.
Highlights
The administration of anesthetics is accompanied with undesired side effects, comprising lung respiratory depression and hypothermia [1]
The increment of UCP2 expression in animals transplanted with bone marrow cells from UCP2 deficient mice was intermediary between that in non-transplanted mice and in animals transplanted with bone marrow cells from wild type mice, suggesting that UCP2 is increased in structural cells and in resident inflammatory/immune cells
We show for the first time that UCP2 responds to a physiological change induced by several anesthetics and a myorelaxant
Summary
The administration of anesthetics is accompanied with undesired side effects, comprising lung respiratory depression and hypothermia [1]. Close relatives of UCP1 (i.e., UCP2 and UCP3) have been isolated in tissues other than BAT [5,6] Their mechanisms of action are still under debate and it has been suggested that they are involved in the regulation of mitochondrial dependent fatty acid oxidation and reactive oxygen production [7]. While UCP3 is mainly expressed in muscle, UCP2 is present in many organs and cell types It is predominantly expressed in the inflammatory/ immune system, in white adipose tissue, in the digestive system, in the lung and in some regions of the brain, including the hypothalamus [8,9]. Because general anaesthesia is associated with immune depression [17], inflammation [18], hypothermia, mitochondrial perturbations [19] and oxidative stress [20], we aimed to investigate the expression and function of UCP2 upon anaesthesia and sedation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Bioenergetics
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
