title: Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice.
abstract: Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS,n= 9) and heterozygous (HbAS,n= 10) SCD (Townes) mice in comparison to control (HbAA,n= 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice (P< 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls (P< 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice.NEW & NOTEWORTHYThe main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD.
authors.affiliation: Aix-Marseille Univ, CNRS, CRMBM, Marseille, France; and benjamin.chatel@live.fr.
authors.forename: Benjamin
authors.identifier: http://orcid.org/0000-0002-8197-1903
authors.initials: B
authors.lastname: Chatel
authors.affiliation: Aix-Marseille Univ, CNRS, CRMBM, Marseille, France; and.|Université Savoie Mont Blanc, Laboratoire Interuniversitaire de Biologie de la Motricité, EA 7424, Chambéry, France.
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Messonnier
authors.affiliation: Université Savoie Mont Blanc, Laboratoire Interuniversitaire de Biologie de la Motricité, EA 7424, Chambéry, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourdé
authors.affiliation: Aix-Marseille Univ, CNRS, CRMBM, Marseille, France; and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vilmen
authors.affiliation: Aix-Marseille Univ, CNRS, CRMBM, Marseille, France; and.
authors.forename: Monique
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Aix-Marseille Univ, CNRS, CRMBM, Marseille, France; and.
authors.forename: David
authors.initials: D
authors.lastname: Bendahan
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000755:Anemia, Sickle Cell / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D010725:Phosphocreatine / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012146:Rest / Q000502:physiology
chemical_list: D006451:Hemoglobin, Sickle; D010725:Phosphocreatine
keywords: exercise intensity; hemoglobin polymerization; muscle energetics; pH; physical activity