| Autor: |
Haq, Syed, Kilter, Heiko, Michael, Ashour, Tao, Jingzang, O'Leary, Eileen, Sun, Xio Ming, Walters, Brian, Bhattacharya, Kausik, Chen, Xin, Cui, Lei, Andreucci, Michele, Rosenzweig, Anthony, Guerrero, J. Luis, Patten, Richard, Liao, Ronglih, Molkentin, Jeffery, Picard, Michael, Bonventre, Joseph V., Force, Thomas |
| Předmět: |
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| Zdroj: |
Nature Medicine; Jul2003, Vol. 9 Issue 7, p944, 8p |
| Abstrakt: |
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] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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