Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction
Само за регистроване кориснике
2005
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG h...earts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.
Кључне речи:
troponin I / calcium sensitizers / phosphorylation / stunning / cross bridge-dependent activationИзвор:
American Journal of Physiology - Heart & Circulatory Physiology, 2005, 289, 5, H2183-H2192Издавач:
- Amer Physiological Soc, Bethesda
Финансирање / пројекти:
- NHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [KO1-HL-67709, P01-HL-62426, R37-HL-22231]
DOI: 10.1152/ajpheart.00520.2005
ISSN: 0363-6135
PubMed: 16024565
WoS: 000232497500052
Scopus: 2-s2.0-27144551306
Колекције
Институција/група
Stomatološki fakultetTY - JOUR AU - Arteaga, GM AU - Warren, CM AU - Milutinović-Smiljanić, Sanja AU - Martin, AF AU - Solaro, RJ PY - 2005 UR - https://smile.stomf.bg.ac.rs/handle/123456789/1249 AB - Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function. PB - Amer Physiological Soc, Bethesda T2 - American Journal of Physiology - Heart & Circulatory Physiology T1 - Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction VL - 289 IS - 5 SP - H2183 EP - H2192 DO - 10.1152/ajpheart.00520.2005 ER -
@article{ author = "Arteaga, GM and Warren, CM and Milutinović-Smiljanić, Sanja and Martin, AF and Solaro, RJ", year = "2005", abstract = "Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.", publisher = "Amer Physiological Soc, Bethesda", journal = "American Journal of Physiology - Heart & Circulatory Physiology", title = "Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction", volume = "289", number = "5", pages = "H2183-H2192", doi = "10.1152/ajpheart.00520.2005" }
Arteaga, G., Warren, C., Milutinović-Smiljanić, S., Martin, A.,& Solaro, R.. (2005). Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction. in American Journal of Physiology - Heart & Circulatory Physiology Amer Physiological Soc, Bethesda., 289(5), H2183-H2192. https://doi.org/10.1152/ajpheart.00520.2005
Arteaga G, Warren C, Milutinović-Smiljanić S, Martin A, Solaro R. Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction. in American Journal of Physiology - Heart & Circulatory Physiology. 2005;289(5):H2183-H2192. doi:10.1152/ajpheart.00520.2005 .
Arteaga, GM, Warren, CM, Milutinović-Smiljanić, Sanja, Martin, AF, Solaro, RJ, "Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction" in American Journal of Physiology - Heart & Circulatory Physiology, 289, no. 5 (2005):H2183-H2192, https://doi.org/10.1152/ajpheart.00520.2005 . .