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Deletion of cytosolic phospholipase A2 promotes striated muscle growth.
- Source :
-
Nature Medicine . Jul2003, Vol. 9 Issue 7, p944. 8p. - Publication Year :
- 2003
-
Abstract
- Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A[sub 2] (PLA[sub 2]) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA[sub 2] is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a[sup -/-] mice, which lack the gene encoding cytosolic PLA[sub 2]. The mechanism underlying this phenotype is that cytosolic PLA[sub 2] negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA[sub 2] leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-ζ, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-ζ, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA[sub 2] and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PHOSPHOLIPASE A2
*STRIATED muscle
*ARACHIDONIC acid
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 9
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 10152484
- Full Text :
- https://doi.org/10.1038/nm891