title: Increased oxidative stress and anaerobic energy release, but blunted Thr172-AMPKα phosphorylation, in response to sprint exercise in severe acute hypoxia in humans.
abstract: AMP-activated protein kinase (AMPK) is a major mediator of the exercise response and a molecular target to improve insulin sensitivity. To determine if the anaerobic component of the exercise response, which is exaggerated when sprint is performed in severe acute hypoxia, influences sprint exercise-elicited Thr(172)-AMPKα phosphorylation, 10 volunteers performed a single 30-s sprint (Wingate test) in normoxia and in severe acute hypoxia (inspired Po(2): 75 mmHg). Vastus lateralis muscle biopsies were obtained before and immediately after 30 and 120 min postsprint. Mean power output and O(2) consumption were 6% and 37%, respectively, lower in hypoxia than in normoxia. O(2) deficit and muscle lactate accumulation were greater in hypoxia than in normoxia. Carbonylated skeletal muscle and plasma proteins were increased after the sprint in hypoxia. Thr(172)-AMPKα phosphorylation was increased by 3.1-fold 30 min after the sprint in normoxia. This effect was prevented by hypoxia. The NAD(+)-to-NADH.H(+) ratio was reduced (by 24-fold) after the sprints, with a greater reduction in hypoxia than in normoxia (P < 0.05), concomitant with 53% lower sirtuin 1 (SIRT1) protein levels after the sprint in hypoxia (P < 0.05). This could have led to lower liver kinase B1 (LKB1) activation by SIRT1 and, hence, blunted Thr(172)-AMPKα phosphorylation. Ser(485)-AMPKα(1)/Ser(491)-AMPKα(2) phosphorylation, a known negative regulating mechanism of Thr(172)-AMPKα phosphorylation, was increased by 60% immediately after the sprint in hypoxia, coincident with increased Thr(308)-Akt phosphorylation. Collectively, our results indicate that the signaling response to sprint exercise in human skeletal muscle is altered in severe acute hypoxia, which abrogated Thr(172)-AMPKα phosphorylation, likely due to lower LKB1 activation by SIRT1.
authors.affiliation: Department of Physical Education, University of Las Palmas de Gran Canaria (Campus Universitario de Tafira Las Palmas de Gran Canaria, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Morales-Alamo
authors.forename: Jesús Gustavo
authors.initials: JG
authors.lastname: Ponce-González
authors.forename: Amelia
authors.initials: A
authors.lastname: Guadalupe-Grau
authors.forename: Lorena
authors.initials: L
authors.lastname: Rodríguez-García
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santana
authors.forename: Maria Roser
authors.initials: MR
authors.lastname: Cusso
authors.forename: Mario
authors.initials: M
authors.lastname: Guerrero
authors.forename: Borja
authors.initials: B
authors.lastname: Guerra
authors.forename: Cecilia
authors.initials: C
authors.lastname: Dorado
authors.forename: José A L
authors.initials: JA
authors.lastname: Calbet
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D015308:Anaerobic Threshold; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D004734:Energy Metabolism; D015444:Exercise; D005080:Exercise Test; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000201:enzymology* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D053580:Muscle Strength; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010766:Phosphorylation; D050050:Protein Carbonylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D052097:Quadriceps Muscle / Q000201:enzymology* / Q000503:physiopathology; D012420:Running; D012720:Severity of Illness Index; D056564:Sirtuin 1 / Q000378:metabolism; D013912:Threonine; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D020690:GTPase-Activating Proteins; D007328:Insulin; C518767:TBC1D4 protein, human; D009243:NAD; D013912:Threonine; D019344:Lactic Acid; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1