{"title":"MnSOD酶敲低小鼠的中枢神经系统氧毒性和血糖水平","authors":"Ricarina Rabinovitz, Mirit Eynan","doi":"10.1016/j.resp.2023.104122","DOIUrl":null,"url":null,"abstract":"<div><p>Many studies have been conducted in the search for the mechanism underlying CNS-oxygen toxicity (OT), which may be fatal when diving with a closed-circuit apparatus. We investigated the influence of hyperbaric oxygen (HBO) on blood glucose level (BGL) in Mn-superoxide dismutase (SOD2) knockdown mice regarding CNS-OT in particular under stress conditions such as hypoglycemia or hyperglycemia. Two groups of mice were used: SOD2 knockdown (Heterozygous, HET) mice and their WT family littermates. Animals were exposed to HBO from 2 up to 5 atmosphere absolute (ATA). Blood samples were drawn before and after each exposure for measurement of BGL. The mice were sacrificed following the final exposure, which was at 5 ATA. We used RT-PCR and Western blot to measure levels of glucose transporter 1 (GLUT1) and hypoxia inducible factor (HIF)1a in the cortex and hippocampus. In the hypoglycemic condition, the HET mice were more sensitive to oxidative stress than the WT. In addition, following exposure to sub-toxic HBO, which does not induce CNS-OT, BGL were higher in the HET mice compared with the WT. The expression of mRNA of GLUT1 and HIF-1a decreased in the hippocampus in the HET mice, while the protein level decreased in the HET and WT following HBO exposure. The results suggest that the higher BGL following HBO exposure especially at SOD2 HET mice is in part due to reduction in GLUT1 as a consequence of lower HIF-1a expression. This may add part to the puzzle of the understanding the mechanism leading to CNS-OT.</p></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CNS-oxygen toxicity and blood glucose levels in MnSOD enzyme knockdown mice\",\"authors\":\"Ricarina Rabinovitz, Mirit Eynan\",\"doi\":\"10.1016/j.resp.2023.104122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Many studies have been conducted in the search for the mechanism underlying CNS-oxygen toxicity (OT), which may be fatal when diving with a closed-circuit apparatus. We investigated the influence of hyperbaric oxygen (HBO) on blood glucose level (BGL) in Mn-superoxide dismutase (SOD2) knockdown mice regarding CNS-OT in particular under stress conditions such as hypoglycemia or hyperglycemia. Two groups of mice were used: SOD2 knockdown (Heterozygous, HET) mice and their WT family littermates. Animals were exposed to HBO from 2 up to 5 atmosphere absolute (ATA). Blood samples were drawn before and after each exposure for measurement of BGL. The mice were sacrificed following the final exposure, which was at 5 ATA. We used RT-PCR and Western blot to measure levels of glucose transporter 1 (GLUT1) and hypoxia inducible factor (HIF)1a in the cortex and hippocampus. In the hypoglycemic condition, the HET mice were more sensitive to oxidative stress than the WT. In addition, following exposure to sub-toxic HBO, which does not induce CNS-OT, BGL were higher in the HET mice compared with the WT. The expression of mRNA of GLUT1 and HIF-1a decreased in the hippocampus in the HET mice, while the protein level decreased in the HET and WT following HBO exposure. The results suggest that the higher BGL following HBO exposure especially at SOD2 HET mice is in part due to reduction in GLUT1 as a consequence of lower HIF-1a expression. This may add part to the puzzle of the understanding the mechanism leading to CNS-OT.</p></div>\",\"PeriodicalId\":20961,\"journal\":{\"name\":\"Respiratory Physiology & Neurobiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory Physiology & Neurobiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1569904823001106\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Physiology & Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1569904823001106","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
CNS-oxygen toxicity and blood glucose levels in MnSOD enzyme knockdown mice
Many studies have been conducted in the search for the mechanism underlying CNS-oxygen toxicity (OT), which may be fatal when diving with a closed-circuit apparatus. We investigated the influence of hyperbaric oxygen (HBO) on blood glucose level (BGL) in Mn-superoxide dismutase (SOD2) knockdown mice regarding CNS-OT in particular under stress conditions such as hypoglycemia or hyperglycemia. Two groups of mice were used: SOD2 knockdown (Heterozygous, HET) mice and their WT family littermates. Animals were exposed to HBO from 2 up to 5 atmosphere absolute (ATA). Blood samples were drawn before and after each exposure for measurement of BGL. The mice were sacrificed following the final exposure, which was at 5 ATA. We used RT-PCR and Western blot to measure levels of glucose transporter 1 (GLUT1) and hypoxia inducible factor (HIF)1a in the cortex and hippocampus. In the hypoglycemic condition, the HET mice were more sensitive to oxidative stress than the WT. In addition, following exposure to sub-toxic HBO, which does not induce CNS-OT, BGL were higher in the HET mice compared with the WT. The expression of mRNA of GLUT1 and HIF-1a decreased in the hippocampus in the HET mice, while the protein level decreased in the HET and WT following HBO exposure. The results suggest that the higher BGL following HBO exposure especially at SOD2 HET mice is in part due to reduction in GLUT1 as a consequence of lower HIF-1a expression. This may add part to the puzzle of the understanding the mechanism leading to CNS-OT.
期刊介绍:
Respiratory Physiology & Neurobiology (RESPNB) publishes original articles and invited reviews concerning physiology and pathophysiology of respiration in its broadest sense.
Although a special focus is on topics in neurobiology, high quality papers in respiratory molecular and cellular biology are also welcome, as are high-quality papers in traditional areas, such as:
-Mechanics of breathing-
Gas exchange and acid-base balance-
Respiration at rest and exercise-
Respiration in unusual conditions, like high or low pressure or changes of temperature, low ambient oxygen-
Embryonic and adult respiration-
Comparative respiratory physiology.
Papers on clinical aspects, original methods, as well as theoretical papers are also considered as long as they foster the understanding of respiratory physiology and pathophysiology.