Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training
Cardiac adaptation to endurance training includes improved contractility by a non-yet clarified mechanism. Since IGF-1 is the main mediator of the physiological response to exercise, we explored its effect on cardiac contractility and the putative involvement of nitric oxide (NO) and CaMKII in contr...
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| Autores principales: | , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2017
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/108322 https://www.jmmc-online.com/article/S0022-2828(17)30292-4/fulltext |
| Aporte de: |
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I19-R120-10915-108322 |
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dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Ciencias Veterinarias IGF-1, nitric oxide synthase 1 CaMKII cardiac contractility exercise training |
| spellingShingle |
Ciencias Médicas Ciencias Veterinarias IGF-1, nitric oxide synthase 1 CaMKII cardiac contractility exercise training Burgos, Juan Ignacio Yeves, Alejandra del Milagro Barrena, Jorge Pablo Portiansky, Enrique Leo Vila Petroff, Martín Gerardo Ennis, Irene Lucía Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| topic_facet |
Ciencias Médicas Ciencias Veterinarias IGF-1, nitric oxide synthase 1 CaMKII cardiac contractility exercise training |
| description |
Cardiac adaptation to endurance training includes improved contractility by a non-yet clarified mechanism. Since IGF-1 is the main mediator of the physiological response to exercise, we explored its effect on cardiac contractility and the putative involvement of nitric oxide (NO) and CaMKII in control and swim-trained mice.
IGF-1 increased cardiomyocyte shortening (128.1 ± 4.6% vs. basal; p ˂ 0.05) and accelerated relaxation (time to 50% relengthening: 49.2 ± 2.0% vs. basal; p ˂ 0.05), effects abrogated by inhibition of: AKT with MK-2206, NO production with the NO synthase (NOS) inhibitor L-NAME and the specific NOS1 inhibitor nitroguanidine (NG), and CaMKII with KN-93. In agreement, an increase in NO in response to IGF-1 (133.8 ± 2.2%) was detected and prevented by both L-NAME and NG but not KN-93, suggesting that CaMKII activation was downstream NO. In addition, we determined CaMKII activity (P-CaMKII) and phosphorylation of its target, Thr17-PLN. IGF-1, by a NO-dependent mechanism, significantly increased both (227.2 ± 29.4% and 145.3 ± 5.4%, respectively) while no changes in the CaMKII phosphorylation site of ryanodine receptor were evident. The improvement in contractility induced by IGF-1 was associated with increased Ca<sup>2+</sup> transient amplitude, rate of decay and SR content. Interestingly, this response was absent in cardiomyocytes from transgenic mice that express a CaMKII inhibitory peptide (AC3-I strain). Moreover, AC3-I mice subjected to swim training did develop physiological cardiac hypertrophy but not the contractile adaptation.
Therefore, we conclude that NO-dependent CaMKII activation plays a critical role in the improvement in contractility induced by IGF-1 and exercise training. Interestingly, this pathway would not contribute to the adaptive hypertrophy. |
| format |
Articulo Articulo |
| author |
Burgos, Juan Ignacio Yeves, Alejandra del Milagro Barrena, Jorge Pablo Portiansky, Enrique Leo Vila Petroff, Martín Gerardo Ennis, Irene Lucía |
| author_facet |
Burgos, Juan Ignacio Yeves, Alejandra del Milagro Barrena, Jorge Pablo Portiansky, Enrique Leo Vila Petroff, Martín Gerardo Ennis, Irene Lucía |
| author_sort |
Burgos, Juan Ignacio |
| title |
Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| title_short |
Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| title_full |
Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| title_fullStr |
Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| title_full_unstemmed |
Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training |
| title_sort |
nitric oxide and camkii: critical steps in the cardiac contractile response to igf-1 and swim training |
| publishDate |
2017 |
| url |
http://sedici.unlp.edu.ar/handle/10915/108322 https://www.jmmc-online.com/article/S0022-2828(17)30292-4/fulltext |
| work_keys_str_mv |
AT burgosjuanignacio nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining AT yevesalejandradelmilagro nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining AT barrenajorgepablo nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining AT portianskyenriqueleo nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining AT vilapetroffmartingerardo nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining AT ennisirenelucia nitricoxideandcamkiicriticalstepsinthecardiaccontractileresponsetoigf1andswimtraining |
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Repositorios |
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