title: Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins during sepsis.
abstract: Altered phosphorylation and Ca(2+) sensitivity of cardiac myofibrillar proteins during different phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). The results show that phosphorylation of troponin I (TnI) was increased by 268% during the early phase (9 h after CLP) but decreased by 46% during the late phase (18 h after CLP) of sepsis. Phosphorylation of C protein was increased by 76% during the early phase but decreased by 41% during the late phase of sepsis. Phosphorylation of myosin light chain-2 (MLC-2) remained unaltered during the early phase but was decreased by 38% during the late phase of sepsis. Phosphorylation of TnT was unaffected during the progression of sepsis. The increases in the phosphorylation of TnI and C protein during early sepsis were associated with the decrease in the Ca(2+) sensitivity of myofilaments and the increases in myocardial changes in tension development (+dP/dt(max)) and cAMP level. The decreases in the phosphorylation of TnI and C protein during late sepsis coincided with the declines in the activities of myofibrillar ATPase, Ca(2+) sensitivity of myofilaments, myocardial +/-dP/dt(max), and cAMP content. The increases and the decreases in the phosphorylation of TnI and C protein, +/-dP/dt(max), and the tissue cAMP level were sensitive to isoproterenol stimulation and propranolol inhibition. These findings suggest that alterations in the phosphorylation of myofibrillar proteins, such as TnI, C protein, and MLC-2, and changes in the activities and the Ca(2+) sensitivity of myofibrillar ATPase may contribute to the altered cardiac function during the progression of sepsis. Furthermore, the sepsis-induced alterations in the phosphorylation and Ca(2+) sensitivity of cardiac myofibrillar proteins were mediated via a beta-adrenergic receptor pathway.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Sciences Center, Beijing 100083, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Wu
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: M S
authors.initials: MS
authors.lastname: Liu
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism*; D024722:Cardiac Myosins; D002352:Carrier Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009210:Myofibrils / Q000737:chemistry / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology; D014020:Tissue Extracts / Q000737:chemistry / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism*; D020107:Troponin T / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D002352:Carrier Proteins; D018994:Myosin Light Chains; D014020:Tissue Extracts; D019210:Troponin I; D020107:Troponin T; C020723:citrate-binding transport protein; C107184:myosin light chain 2; D000251:Adenosine Triphosphatases; D024722:Cardiac Myosins; D007545:Isoproterenol; D002118:Calcium