title: The effect of standard chow and reduced hexokinase II on growth, cardiac and skeletal muscle hexokinase and low-flow cardiac ischaemia-reperfusion injury.
abstract: In the present study, we examined whether standard chow (SDS versus Purina 5001; both low fat, high carbohydrate) and reductions in hexokinase (HK) II (wild-type versus HKII(+/-) mice) affect (1) growth parameters, (2) HK levels in cardiac and skeletal muscle and (3) low-flow cardiac ischaemia-reperfusion (IR) injury. Total HK activity and HKI and HKII expressions were determined, and low-flow IR injury was examined in isolated hearts subjected to 40 min 5% low-flow ischaemia and 120 min reperfusion. Standard chow, but not HKII reductions, significantly affected body weight, heart weight and cardiac hypertrophy. Both standard chow and reduced HKII diminished total cardiac and skeletal muscle HK activity. For the heart, the Purina chow-induced decrease in total HK activity was through decreases in HKI expression, whereas for skeletal muscle post-translational mechanisms are suggested. Both standard chow and reduced HKII demonstrated a non-significant trend for affecting cardiac IR damage. However, the low-flow ischaemia model was associated with mild sublethal injury only (∼1% cell death). In conclusion, standard chow affects body weight, heart weight and HK activity and HKI expression in the heart, without altering HKII expression. This implicates standard chow as an important factor in genomic, physiological research models and demonstrates that large differences in fat or carbohydrates in the diet are not necessary to affect growth. In a cardiac low-flow IR model, resulting in only mild injury, standard chow or reduced HKII does not significantly affect IR damage.
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Department of Anesthesiology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Smeele
authors.forename: Leontien H
authors.initials: LH
authors.lastname: ter Horst
authors.forename: Anneke
authors.initials: A
authors.lastname: Koeman
authors.forename: Sami
authors.initials: S
authors.lastname: Heikkinen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.forename: Coert J
authors.initials: CJ
authors.lastname: Zuurbier
mesh_terms: D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000662:veterinary; D005260:Female; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D009929:Organ Size; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: C515658:HK1 protein, mouse; D006593:Hexokinase