Ca2+-independent phospholipase A2 is a novel determinant of store-operated Ca2+ entry
| Autor: | Peter Csutora, Sergey I. Zakharov, Elena S. Trepakova, Victoria M. Bolotina, Tarik Smani, Endri Leno |
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| Rok vydání: | 2003 |
| Předmět: |
Blood Platelets
Vascular smooth muscle Thapsigargin Patch-Clamp Techniques Phosphodiesterase Inhibitors Myocytes Smooth Muscle Naphthalenes Biochemistry Jurkat cells Phospholipases A Membrane Potentials Group VI Phospholipases A2 chemistry.chemical_compound Jurkat Cells Mice Phospholipase A2 BAPTA Animals Humans Molecular Biology Aorta SOC channels Manganese biology Chemistry Cell Biology Transfection Oligonucleotides Antisense Cell biology Rats Electrophysiology Phospholipases A2 Pyrones biology.protein Calcium Calcium Channels Rabbits |
| Zdroj: | The Journal of biological chemistry. 278(14) |
| ISSN: | 0021-9258 |
| Popis: | Store-operated cation (SOC) channels and capacitative Ca(2+) entry (CCE) play very important role in cellular function, but the mechanism of their activation remains one of the most intriguing and long lasting mysteries in the field of Ca(2+) signaling. Here, we present the first evidence that Ca(2+)-independent phospholipase A(2) (iPLA(2)) is a crucial molecular determinant in activation of SOC channels and store-operated Ca(2+) entry pathway. Using molecular, imaging, and electrophysiological techniques, we show that directed molecular or pharmacological impairment of the functional activity of iPLA(2) leads to irreversible inhibition of CCE mediated by nonselective SOC channels and by Ca(2+)-release-activated Ca(2+) (CRAC) channels. Transfection of vascular smooth muscle cells (SMC) with antisense, but not sense, oligonucleotides for iPLA(2) impaired thapsigargin (TG)-induced activation of iPLA(2) and TG-induced Ca(2+) and Mn(2+) influx. Identical inhibition of TG-induced Ca(2+) and Mn(2+) influx (but not Ca(2+) release) was observed in SMC, human platelets, and Jurkat T-lymphocytes when functional activity of iPLA(2) was inhibited by its mechanism-based suicidal substrate, bromoenol lactone (BEL). Moreover, irreversible inhibition of iPLA(2) impaired TG-induced activation of single nonselective SOC channels in SMC and BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)-induced activation of whole-cell CRAC current in rat basophilic leukemia cells. Thus, functional iPLA(2) is required for activation of store-operated channels and capacitative Ca(2+) influx in wide variety of cell types. |
| Databáze: | OpenAIRE |
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