Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice
| Autor: | Anneke Koeman, Coert J. Zuurbier, Arnold de Haan, Gert Schaart, Rick Bezemer, Can Ince, Kirsten M. Smeele, Markku Laakso, Maarten R. Drost, Markus W. Hollmann, Otto Eerbeek, Sami Heikkinen |
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| Přispěvatelé: | Anesthesiology, Medical Biology, Biomedical Engineering and Physics, Translational Physiology, Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, Kinesiology, Research Institute MOVE, Faculteit der Geneeskunde, Nutrition and Movement Sciences, Anesthesiologie, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting |
| Rok vydání: | 2010 |
| Předmět: |
Male
Cell death medicine.medical_specialty Programmed cell death Physiology Clinical Biochemistry Ischemia Molecular and Genomic Physiology Biology Mice chemistry.chemical_compound SDG 3 - Good Health and Well-being In vivo Hexokinase Internal medicine Lactate dehydrogenase Physiology (medical) medicine Animals Receptor Mice Knockout Sex Characteristics Skeletal muscle Muscle ischemia medicine.disease Mitochondria Mice Inbred C57BL Endocrinology medicine.anatomical_structure chemistry Reperfusion Injury Muscle Female Reperfusion injury |
| Zdroj: | Pflugers Archiv, 459(5), 705-712. Springer Verlag Pflügers Archiv European Journal of Physiology, 459(5), 705-712. Springer Verlag Plügers Archiv, 459(5), 705-712. Springer Verlag Smeele, K M, Eerbeek, O, Koeman, A, Bezemer, R, Ince, C, Heikkinen, S, Laakso, M, de Haan, A, Schaart, G, Drost, M R, Hollmann, M W & Zuurbier, C J 2010, ' Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice ', Pflügers Archiv European Journal of Physiology, vol. 459, no. 5, pp. 705-712 . https://doi.org/10.1007/s00424-010-0787-3 Pflugers Archiv-European Journal of Physiology, 459(5), 705-712. Springer Verlag Pflugers Archiv |
| ISSN: | 0031-6768 |
| DOI: | 10.1007/s00424-010-0787-3 |
| Popis: | Cellular studies have demonstrated a protective role of mitochondrial hexokinase against oxidative insults. It is unknown whether HK protective effects translate to the in vivo condition. In the present study, we hypothesize that HK affects acute ischemia-reperfusion injury in skeletal muscle of the intact animal. Male and female heterozygote knockout HKII (HK(+/-)), heterozygote overexpressed HKII (HK(tg)), and their wild-type (WT) C57Bl/6 littermates mice were examined. In anesthetized animals, the left gastrocnemius medialis (GM) muscle was connected to a force transducer and continuously stimulated (1-Hz twitches) during 60 min ischemia and 90 min reperfusion. Cell survival (%LDH) was defined by the amount of cytosolic lactate dehydrogenase (LDH) activity still present in the reperfused GM relative to the contralateral (non-ischemic) GM. Mitochondrial HK activity was 72.6 +/- 7.5, 15.7 +/- 1.7, and 8.8 +/- 0.9 mU/mg protein in male mice, and 72.7 +/- 3.7, 11.2 +/- 1.4, and 5.9 +/- 1.1 mU/mg in female mice for HK(tg), WT, and HK(+/-), respectively. Tetanic force recovery amounted to 33 +/- 7% for male and 17 +/- 4% for female mice and was similar for HK(tg), WT, and HK(+/-). However, cell survival was decreased (p = 0.014) in male HK(+/-) (82 +/- 4%LDH) as compared with WT (98 +/- 5%LDH) and HK(tg) (97 +/- 4%LDH). No effects of HKII on cell survival was observed in female mice (92 +/- 2% LDH). In conclusion, in this mild model of acute in vivo ischemia-reperfusion injury, a partial knockout of HKII was associated with increased cell death in male mice. The data suggest for the first time that HKII mediates skeletal muscle ischemia-reperfusion injury in the intact male animal. |
| Databáze: | OpenAIRE |
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