Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes

Sekharam, Madhavi; Cunnick, Joan E.; Wu, Jie

doi:10.1042/bj3460751

Cited by 25 publications

(1 citation statement)

References 26 publications

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“…The duration of a [Ca 2+ ] i transient depends on the balance of [Ca 2+ ] i extrusion from the cytosol by [Ca 2+ ] i pumps (such as the plasma membrane Ca 2+ ATPase, PMCA) and [Ca 2+ ] i re‐entry into the ER through SERCA pumps. Both PMCA and SERCA activity may be impaired in NHEK stimulated with LPA, given that LPA has been shown to induce H 2 O 2 production in HaCaT keratinocytes 32 and H 2 O 2 can inhibit PMCA 33 and SERCA 34 activity.…”

Section: Discussionmentioning

confidence: 99%

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

Ross¹,

Parker²,

Whitaker³

et al. 2007

Br J Dermatol

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BackgroundIn 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.ObjectivesThis study was designed to determine if pharmacological inhibition of calcium-independent phospholipase A (iPLA2) impairs ACE in normal human epidermal keratinocytes.MethodsConfocal 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.ResultsBoth 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 μmol 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 iPLA2. These findings indicate that iPLA2 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.ConclusionOur results demonstrate for the first time an important role for iPLA2 in regulating ACE in primary human keratinocytes.

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Section: Discussionmentioning

confidence: 99%

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

Ross¹,

Parker²,

Whitaker³

et al. 2007

Br J Dermatol

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Redox signaling and the MAP kinase pathways

2003

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The mitogen-activated protein (MAP) kinases are a large family of proline-directed, serine/threonine kinases that require tyrosine and threonine phosphorylation of a TxY motif in the activation loop for activation through a phosphorylation cascade involving a MAPKKK, MAPKK and MAPK, often referred to as the MAP kinase module. Three separate such modules have been identified, based on the TxY motif of the MAP kinase and the dual-specificity kinases that strictly phosphorylate their specific TxY sequence. They are the extracellular signal regulated kinases (ERKs), c-jun N-terminal kinases (JNKs) and p38 MAPKs. The ERKs are mainly associated with proliferation and differentiation while the JNKs and p38MAP kinases regulate responses to cellular stresses. Redox homeostasis is critical for proper cellular function. While reactive oxygen species (ROS) and oxidative stress have been implicated in injury, a rapidly growing literature suggests that a transient increase in ROS levels is an important mediator of proliferation and results in activation of various signaling molecules and pathways, among which the MAP kinases. This review will summarize the role of ROS in MAP kinase activation in various systems, including in macrophages, cells of myeloid origin that play an essential role in inflammation and express a multi-component NADPH oxidase that catalyzes the receptor-regulated production of ROS.

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Thrombin induces expression of cytokine‐induced SH2 protein (CIS) in rat brain astrocytes: Involvement of phospholipase A₂, cyclooxygenase, and lipoxygenase

Yang

Jou

et al. 2004

Glia

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Previously we have reported that thrombin induces inflammatory mediators in brain glial cells (Ryu et al. 2000. J Biol Chem 275:29955). In the present study, we found that thrombin induced a negative regulator of a cytokine signaling molecule, cytokineinduced SH2 protein (CIS), in rat brain astrocytes. In response to thrombin, CIS expression was increased at both the mRNA and protein levels. Although STAT5 is known to regulate CIS expression, thrombin did not activate STAT5, and inhibitors of JAK2 (AG490) and JAK3 (WHI-P97 and WHI-P154) had little effect on thrombin-induced CIS expression. In contrast, cytosolic phospholipase A 2 (cPLA 2 ), cyclooxygenase (COX), and lipoxygenase (LO) play a role in CIS expression, since inhibitors of cPLA 2 , cyclooxygenase (COX), and LO significantly reduced CIS expression. Reactive oxygen species (ROS) scavengers (N-acetylcysteine [NAC] and trolox) reduced thrombin-induced CIS expression, and inhibitors of COX and LO reduced ROS produced by thrombin. Furthermore, prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ), products of COX and LO, respectively, potentiated thrombin-induced CIS expression, indicating that ROS, and PGE 2 and LTB 4 generated by COX and LO, mediate CIS expression. Since interferon-␥ (IFN-␥)-induced GAS-luciferase activity and tyrosine phosphorylation of STAT1 and STAT3 were lower in CIS-transfected cells compared to control vector-transfected cells, CIS could have anti-inflammatory activity. These data suggest that thrombin-stimulation of ROS and prostaglandin and leukotriene production via the cPLA 2 , COX and LO pathways results in CIS expression. More importantly, CIS expression may be a negative feedback mechanism that prevents prolonged inflammatory responses.

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Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes

Cited by 25 publications

References 26 publications

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

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

Redox signaling and the MAP kinase pathways

Thrombin induces expression of cytokine‐induced SH2 protein (CIS) in rat brain astrocytes: Involvement of phospholipase A₂, cyclooxygenase, and lipoxygenase

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Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes

Cited by 25 publications

References 26 publications

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

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

Redox signaling and the MAP kinase pathways

Thrombin induces expression of cytokine‐induced SH2 protein (CIS) in rat brain astrocytes: Involvement of phospholipase A2, cyclooxygenase, and lipoxygenase

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Thrombin induces expression of cytokine‐induced SH2 protein (CIS) in rat brain astrocytes: Involvement of phospholipase A₂, cyclooxygenase, and lipoxygenase