Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0151814 (
coronary occlusion
)
3,687
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sphingosine 1-phosphate
(
S1P
) 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
S1P
receptor subtypes were deleted. Mice lacking either
S1P
(2) or
S1P
(3) 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
S1P
(2,3) receptor double-knockout mice, infarct size following I/R was increased by >50%. I/R leads to activation of ERK, JNK, and p38 MAP kinases; however, these responses were not diminished in
S1P
(2,3) receptor knockout compared with WT mice. In contrast, activation of Akt in response to I/R was markedly attenuated in
S1P
(2,3) receptor knockout mouse hearts. Neither
S1P
(2) nor
S1P
(3) 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
S1P
(2) and
S1P
(3) 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
S1P
(2) or
S1P
(3) receptor knockout mice and completely abolished in the
S1P
(2,3) receptor double-knockout myocytes. Our data demonstrate that activation of
S1P
(2) and
S1P
(3) 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.
...
PMID:Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. 1729 97
