Document Detail


Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice.
MedLine Citation:
PMID:  20182739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kirsten M Smeele; Otto Eerbeek; Anneke Koeman; Rick Bezemer; Can Ince; Sami Heikkinen; Markku Laakso; Arnold de Haan; Gert Schaart; Maarten R Drost; Markus W Hollmann; Coert J Zuurbier
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Publication Detail:
Type:  Journal Article     Date:  2010-02-25
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  459     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-07-07     Revised Date:  2010-09-30    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  705-12     Citation Subset:  IM    
Affiliation:
Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anaesthesiology, Academic Medical Center, Meibergdreef 9, 1105 Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Hexokinase / genetics*,  metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Reperfusion Injury / genetics*,  metabolism*
Sex Characteristics
Chemical
Reg. No./Substance:
EC 2.7.1.1/Hexokinase
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