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Inhibition of calcium-independent phospholipase A impairs agonist-induced calcium entry in keratinocytes

Ross, K, Parker, G, Whitaker, M and Reynolds, MJ (2007) Inhibition of calcium-independent phospholipase A impairs agonist-induced calcium entry in keratinocytes. British Journal of Dermatology, 158 (1). pp. 31-37. ISSN 1365-2133

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Open Access URL: https://doi.org/10.1111/j.1365-2133.2007.08298.x (Published version)


BACKGROUND: In many cells, depletion of intracellular calcium (Ca2+) reservoirs triggers Ca2+ entry through store-operated Ca2+ channels in the plasma membrane. However, the mechanisms of agonist-induced calcium entry (ACE) in keratinocytes are not fully understood. OBJECTIVES: This study was designed to determine if pharmacological inhibition of calcium-independent phospholipase A (iPLA(2)) impairs ACE in normal human epidermal keratinocytes. METHODS: Confocal laser scanning microscopy was used to monitor the dynamics of Ca2+ signalling in keratinocytes loaded with the calcium-sensitive dye Fluo-4. Cells were stimulated with extracellular nucleotides [adenosine triphosphate (ATP) or uridine triphosphate (UTP)] or with lysophosphatidic acid (LPA), a bioactive lipid that regulates keratinocyte proliferation and differentiation. RESULTS: Both ATP and UTP induced Ca2+ release in primary human keratinocytes. This was not followed by robust Ca2+ influx when the experiments were performed in low Ca2+ (70 micromol L(-1)) medium. Upon elevation of extracellular Ca2+ to 1.2 mmol L(-1), however, a biphasic response consisting of an initial Ca2+ peak followed by an elevated plateau was observed. The plateau phase was inhibited when cells were treated with bromoenol lactone, a specific pharmacological inhibitor of iPLA(2). These findings indicate that iPLA(2) activity is required for ACE in keratinocytes. LPA also evoked Ca2+ release in keratinocytes but failed to induce sustained Ca2+ entry even when extracellular Ca2+ was elevated to 1.2 mmol L(-1). CONCLUSION: Our results demonstrate for the first time an important role for iPLA(2) in regulating ACE in primary human keratinocytes.

Item Type: Article
Uncontrolled Keywords: 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Date Deposited: 31 Aug 2021 09:02
Last Modified: 04 Sep 2021 05:06
DOI or Identification number: 10.1111/j.1365-2133.2007.08298.x
URI: https://researchonline.ljmu.ac.uk/id/eprint/15409

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