The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Ischemic preconditioning protects by activating prosurvival kinases at reperfusion
Abstract
Pharmacological activation of the prosurvival kinases Akt and ERK-1/2 at reperfusion, after a period of lethal ischemia, protects the heart against ischemia-reperfusion injury. We hypothesized that ischemic preconditioning (IPC) protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion. In isolated perfused Sprague-Dawley rat hearts subjected to 35 min of lethal ischemia, the phosphorylation states of Akt, ERK-1/2, and p70 S6 kinase (p70S6K) were determined after 15 min of reperfusion, and infarct size was measured after 120 min of reperfusion. IPC induced a biphasic response in Akt and ERK-1/2 phosphorylation during the preconditioning and reperfusion phases after the period of lethal ischemia. IPC induced a fourfold increase in Akt, ERK-1/2, and p70S6K phosphorylation at reperfusion and reduced the infarct risk-to-volume ratio (56.9 ± 5.7 and 20.9 ± 3.6% for control and IPC, respectively, P < 0.01). Inhibiting the IPC-induced phosphorylation of Akt, ERK-1/2, and p70S6K at reperfusion with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 or the MEK-1/2 inhibitor PD-98059 abrogated IPC-induced protection (46.3 ± 5.8, 49.2 ± 4.0, and 20.9 ± 3.6% for IPC + LY-294002, IPC + PD-98059, and IPC, respectively, P < 0.01), demonstrating that the phosphorylation of these kinases at reperfusion is required for IPC-induced protection. In conclusion, we demonstrate that the reperfusion phase following sustained ischemia plays an essential role in mediating IPC-induced protection. Specifically, we demonstrate that IPC protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion.
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Cites
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Self-citationThe Phosphatidylinositol 3-Kinase (PI3K)-Akt Pathway Suppresses Bax Translocation to Mitochondria
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Ischemic Preconditioning Activates Phosphatidylinositol-3-Kinase Upstream of Protein Kinase C
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Protein kinase C. Its role in ischemic preconditioning in the rat.
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MicroRNAs in Development and Disease
Sayed, D., & Abdellatif, M. (2011) · Physiological Reviews · doi:10.1152/physrev.00006.2010 · Cited by 1,078
Bøtker, H. E., Kharbanda, R., Schmidt, M. R., Bøttcher, M., Kaltoft, A. K., Terkelsen, C. J., Munk, K., Andersen, N. H., Hansen, T. M., Trautner, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(09)62001-8 · Cited by 989
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Rapid DNA methylation changes after exposure to traffic particles
Baccarelli, A., Wright, R. O., Bollati, V., Tarantini, L., Litonjua, A. A., Suh, H. H., Zanobetti, A., Sparrow, D., Vokonas, P. S., & Schwartz, J. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200807-1097oc · Cited by 653
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Metadata
- Authors
- Hausenloy, D. J., Tsang, A., Mocanu, M. M., & Yellon, D. M.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2005-02
- Volume
- 288
- Issue
- 2
- Pages
- H971-H976
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2116899872
- Cited by
- 512
- References
- 17
- FWCI
- 21.56
- Type
- journal article
- Language
- en
- Open access
- closed
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