Calcium-independent phospholipase A(2) mediates CREB phosphorylation and c-fos expression during ischemia.

Abstract

In isolated, perfused adult rat hearts, global ischemia increased the phosphorylation of cAMP response element-binding protein (CREB) relative to control levels, and this phosphorylation was reversed with reperfusion. CREB phosphorylation elicited by 5 min of global ischemia was sensitive to treatments with the calcium-independent phospholipase A(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) and occurred in the absence of increases in myocardial cAMP content. In contrast, CREB phosphorylation elicited by 15 min of global ischemia was likely mediated by elevated cAMP levels. The expression of c-fos, in response to brief myocardial ischemia, was also sensitive to BEL treatment. The induction of iPLA(2)-mediated CREB phosphorylation was further substantiated by the observations that lysoplasmenylcholine increased both the phosphorylation of CREB and the induction of c-fos expression in the absence and presence of BEL. CREB phosphorylation in both ischemic hearts and lysoplasmenylcholine-perfused hearts was inhibited by pretreatment of hearts with the specific cAMP-dependent protein kinase (PKA) inhibitor H-89. Taken together, these data demonstrate that iPLA(2) mediates CREB phosphorylation through a PKA-dependent pathway during brief periods of myocardial ischemia, possibly through the formation of lysophospholipids.

• Authors: S D Williams, D A Ford
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 281 Issue 1 Pg. H168-76 (Jul 2001) ISSN: 0363-6135 [Print] United States
• PMID: 11406482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Lysophospholipids
• Naphthalenes
• Proto-Oncogene Proteins c-fos
• Pyrones
• RNA, Messenger
• lysoplasmalogens
• 8-Bromo Cyclic Adenosine Monophosphate
• 6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one
• Phospholipases A
• Calcium

Topics

• 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
• Animals
• Biological Transport
• Calcium (physiology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Lysophospholipids (pharmacology)
• Male
• Myocardial Ischemia (metabolism)
• Naphthalenes (pharmacology)
• Phospholipases A (metabolism, physiology)
• Phosphorylation
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Pyrones (pharmacology)
• RNA, Messenger (antagonists & inhibitors)
• Rats
• Rats, Sprague-Dawley