The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion
Open accessAbstract
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that also modulates physiologic cell signaling pathways.MIF is expressed in cardiomyocytes and limits cardiac injury by enhancing AMPK activity during ischemia.Reperfusion injury is mediated in part by activation of the stress kinase JNK, but whether MIF modulates JNK in this setting is unknown.We examined the role of MIF in regulating JNK activation and cardiac injury during experimental ischemia/reperfusion in mouse hearts.Isolated perfused Mif -/-hearts had greater contractile dysfunction, necrosis, and JNK activation than WT hearts, with increased upstream MAPK kinase 4 phosphorylation, following ischemia/reperfusion.These effects were reversed if recombinant MIF was present during reperfusion, indicating that MIF deficiency during reperfusion exacerbated injury.Activated JNK acts in a proapoptotic manner by regulating BCL2-associated agonist of cell death (BAD) phosphorylation, and this effect was accentuated in Mif -/-hearts after ischemia/reperfusion. Similar detrimental effects of MIF deficiency were observed in vivo following coronary occlusion and reperfusion in Mif -/-mice.Importantly, excess JNK activation also was observed after hypoxia-reoxygenation in human fibroblasts homozygous for the MIF allele with the lowest level of promoter activity.These data indicate that endogenous MIF inhibits JNK pathway activation during reperfusion and protects the heart from injury.These findings have clinical implications for patients with the low-expression MIF allele. Results Endogenous MIF regulates JNK activation through the CD74 receptor during ischemia/reperfusion.Isolated, perfused WT and Mif -/-hearts were subjected to global ischemia for 15 minutes, followed by up to 30 minutes of reperfusion, in order to determine the role of Conflict of interest: Yale University has applied for a patent describing the use of MIF genotyping and MIF-directed therapies in cardiac ischemia injury.
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SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558
The JNK signal transduction pathway
Weston, C. R., & Davis, R. J. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.001 · Cited by 1,021
Russell, R. R., Li, J., Coven, D. L., Pypaert, M., Zechner, C., Palmeri, M., Giordano, F. J., Mu, J., Birnbaum, M. J., & Young, L. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19297 · Cited by 738
Self-citationMiller, E. J., Li, J., Leng, L., McDonald, C., Atsumi, T., Bucala, R., & Young, L. H. (2008) · Nature · doi:10.1038/nature06504 · Cited by 429
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Cited by
Ischemia and reperfusion—from mechanism to translation
Eltzschig, H. K., & Eckle, T. (2011) · Nature Medicine · doi:10.1038/nm.2507 · Cited by 3,382
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Del Re, D. P., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 961
AMP-activated protein kinase regulation and biological actions in the heart
Zaha, V. G., & Young, L. H. (2012) · Circulation Research · doi:10.1161/circresaha.111.255505 · Cited by 279
Self-citationCardiokines: recent progress in elucidating the cardiac secretome
Shimano, M., Ouchi, N., & Walsh, K. (2012) · Circulation · doi:10.1161/circulationaha.112.150656 · Cited by 116
Bardella, C., Olivero, M., Lorenzato, A., Geuna, M., Adam, J., O'Flaherty, L., Rustin, P., Tomlinson, I., Pollard, P. J., & Di Renzo, M. F. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06160-11 · Cited by 33
Metadata
- Authors
- Qi, D., Hu, X., Wu, X., Merk, M., Leng, L., Bucala, R., & Young, L. H.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-12-01
- Volume
- 119
- Issue
- 12
- Pages
- 3807-3816
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2117810566
- Cited by
- 174
- References
- 4
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Qi, D., Hu, X., Wu, X., Merk, M., Leng, L., Bucala, R., & Young, L. H. (2009). Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. Journal of Clinical Investigation. https://doi.org/10.1172/jci39738
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