Defining the Role of Protein Kinase c in Calcium-ionophore-(A23187)-Mediated Activation of Phospholipase A2 in Pulmonary Endothelium
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Defining the Role of Protein Kinase c in Calcium-ionophore-(A23187)-Mediated
Activation of Phospholipase A2 in Pulmonary Endothelium
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| Creator |
Sanyal, Tapati
Michael, John R Chakraborti, Sajal |
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| Subject |
Infectious Diseases and Immunology
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| Description |
We sought to investigate the mechanisms by which the calcium ionophore A23187 triggers arachidonic acid release in bovine pulmonary endothelial cells and to test the hypothesis that protein kinase C is involved in this process. Our results indicate that the mechanism by which A23187 increases phospholipase A2 activity and arachidonic acid release in bovine pulmonary arterial endothelial cells depends upon the concentration studied. At concentrations of 1 pM and 2.5 pM, A23187 increases phospholipase A2 activity and arachidonic acid release without stimulating protein kinase C. At membrane-bound protein kinase C. To test the hypothesis that these doses of A23187 increase phospholipase A2 activity by stimulating protein kinase C, we studied the effect of prior treatment with the protein kinase C inhibitor sphingosine. Sphingosine inhibits the increase in phospholipase A2 activity and arachidonic acid release caused by A23187 over the range 5 - 12.5 pM. To investigate further the potential role of protein kinase C, we studied the effects of the inactive phorbol ester 4a-phorbol 12P-myristate 13aacetate (4a-PMA) and an active phorbol ester 4P-phorbol 12P-myristate 13a-acetate (48 PMA). concentrations of 5 - 12.5 pM, A23187 increases arachidonic acid release and phospholipase A2 activity in conjunction with a dose-dependent activation of Neither 4a-PMA nor 4P-PMA affected basal arachidonic acid release. 4a-PMA also did not augment the effects of A23187. In contrast, 4P-PMA significantly augments the increase in phospholipase A2 activity and arachidonic acid release caused by lower doses of A231 87. Under these conditions,sphingosine completely inhibits the stimulatory effects of 4P-PMA on protein kinase C translocation,phospholipase A2 and arachidonic acid release. Thus, at low doses (1 pM and 2.5 pM) A23187 increases phospholipase A, activity and arachidonic acid release by a mechanism that does not involve protein kinase C. At these A23187 doses, activating membrane-bound protein kinase C with 4P-PMA causes a synergistic increase in phospholipase Az activity and arachdonic acid release. At higher doses (5 - 12.5 pM), A23187 acts in large part by stimulating protein kinase C translocation. Overall,our results indicate that activating membrane-bound protein kinase C by itself is an insufficient stimulus to increase phospholipase A, activity and arachidonic acid release in pulmonary endothelial cells, but activating protein kinase C can substantially augment the increase in phospholipase A2 activity and arachidonic acid caused by a small increase in intracellular calcium.
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| Publisher |
Blackwell Publishing
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| Date |
1992
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1804/1/EUROPEAN_JOURNAL_OF_BIOCHEMISTRY___206_(_3)_965%2D972_;1992[27].pdf
Sanyal, Tapati and Michael, John R and Chakraborti, Sajal (1992) Defining the Role of Protein Kinase c in Calcium-ionophore-(A23187)-Mediated Activation of Phospholipase A2 in Pulmonary Endothelium. European Journal Of Biochemistry, 206 (3). pp. 965-972. |
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| Relation |
http://dx.doi.org/
http://www.eprints.iicb.res.in/1804/ |
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