Sphingosine 1-phosphate S1P^sub 2^ and S1P^sub 3^ receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 292; no. 6; p. H2944
• Main Authors: Means, Christopher K, Chun-Yang, Xiao, Li, Zhuangjie, Zhang, Tong
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.06.2007
• Subjects: Cardiology; Cardiovascular disease; Clinical outcomes; Heart; Phosphates; Rodents
• ISSN: 0363-6135; 1522-1539

Sphingosine 1-phosphate (S 1P) is released at sites of tissue injury and effects cellular responses through activation of G protein-coupled receptors. The role of S1P in regulating cardiomyocyte survival following in vivo myocardial ischemia-reperfusion (I/R) injury was examined by using mice in which specific ... receptor subtypes were deleted. Mice lacking either ... or ... receptors and subjected to 1-h coronary occlusion followed by 2 h of reperfusion developed infarcts equivalent to those of wild-type (WT) mice. However, in ... receptor double-knockout mice, infarct size following hR was increased by >50%. hR leads to activation of ERK, JNK, and p38 MAP kinases; however, these responses were not diminished in ... receptor knockout compared with WT mice. In contrast, activation of Akt in response to hR was markedly attenuated in ... receptor knockout mouse hearts. Neither ... nor ... receptor deletion alone impaired I/R-induced Akt activation, which suggests redundant signaling through these receptors and is consistent with the finding that deletion of either receptor alone did not increase I/R injury. The involvement of cardiomyocytes in ... and ... receptor mediated activation of Akt was tested by using cells from WT and S1P receptor knockout hearts. Akt was activated by S1P, and this was modestly diminished in cardiomyocytes from ... or ... receptor knockout mice and completely abolished in the ... receptor double-knockout myocytes. Our data demonstrate that activation of ... and ... receptors plays a significant role in protecting cardiomyocytes from I/R damage in vivo and implicate the release of S1P and receptor- mediated Akt activation in this process. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)