Protein kinase C-α and -δ are required for NADPH oxidase activation in WKYMVm-stimulated IMR90 human fibroblasts

Iaccio, Annalisa; Collinet, Claudio; Gesualdi, Nicola Montesano; Ammendola, Rosario

doi:10.1016/j.abb.2006.11.009

Cited by 24 publications

(20 citation statements)

References 51 publications

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“…PKCδ was recently shown to play a central role in the regulation of NADPH oxidase activation in non-neuronal systems (Fan et al, 2005;Zhao et al, 2005;Iaccio et al, 2006;Waki et al, 2006) in addition to Rac1 and Rac2. In these studies, PKCδ regulated NADPH oxidase activity by up-regulation of NOX1 subunit, a homologue of the catalytic subunit gp91 phox (NOX1), at the mRNA level via epidermal growth factor.…”

Section: Discussionmentioning

confidence: 99%

“…In these studies, PKCδ regulated NADPH oxidase activity by up-regulation of NOX1 subunit, a homologue of the catalytic subunit gp91 phox (NOX1), at the mRNA level via epidermal growth factor. PKCδ also regulates the phosphorylation and translocation of the p67 phox subunit to the plasma membrane to activate the gp91 phox catalytic subunit (Fan et al, 2005;Zhao et al, 2005;Iaccio et al, 2006;Waki et al, 2006). Taken together, PKCδ and NADPH oxidase possibly interact to accelerate oxidative damage in the nigral dopaminergic system.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

et al. 2007

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Oxidative stress is widely recognized as a key mediator of degenerative processes in Parkinson's disease (PD). Recently, we demonstrated that the dopaminergic toxin MPP + initiates oxidative stress to cause caspase-3-dependent apoptotic cell death in mesencephalic dopaminergic neuronal (N27) cells. In this study, we determined the source of reactive oxygen species (ROS) produced during MPP + -induced apoptotic cell death. In addition to mitochondria, plasma membrane NADPH oxidase is considered a major producer of ROS inside the cell. Here, we show that N27 cells express key NADPH oxidase subunits gp91 phox and p67 phox . We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000 μM), apocynin (100-1000 μM), and diphenylene iodonium (DPI, 3-30 μM), to inhibit intrinsic NADPH oxidase activity in N27 cells. Flow cytometric analysis using the ROS-sensitive dye hydroethidine revealed that AEBSF blocked 300 μM MPP + -induced ROS production for over 45 min in N27 cells, in a dose-dependent manner. Further treatment with DPI, apocynin, and SOD also blocked MPP + -induced ROS production. In Sytox cell death assays, co-treatment with AEBSF, apocynin, or DPI for 24 hr significantly suppressed MPP + -induced cytotoxic cell death. Similarly, co-treatment with these inhibitors also significantly attenuated MPP + -induced increases in caspase-3 enzymatic activity. Furthermore, quantitative DNA fragmentation ELISA assays revealed that AEBSF, DPI, and apocynin rescue N27 cells from MPP + -induced apoptotic cell death. Together, these results indicate for the first time that intracellular ROS generated by NAPDH oxidase are present within the mesencephalic neuronal cells, and are a key determinant of MPP + -mediated dopaminergic degeneration in in vitro models of dopaminergic degeneration. This study supports a critical role of NADPH oxidase in the oxidative damage in PD; targeting this enzyme may lead to novel therapies for PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

et al. 2007

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“…We demonstrated that in IMR90 human fibroblasts, binding of WKYMVm to FPRL1, which is expressed in these cells [34], induces superoxide generation consequent to MEK-and PTX-dependent serine phosphorylation and membrane translocation of the regulatory cytosolic NADPH oxidase subunit p47 phox [34]. In the same cells WKYMVm activates also selected protein kinase C (PKC) isoforms required for NADPH oxidase-dependent superoxide generation [35].…”

Section: Formyl-peptide Receptorsmentioning

confidence: 97%

Expression and Signaling of Formyl-Peptide Receptors in the Brain

2010

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The human formyl-peptide receptor (FPR) and its variants FPRL1 and FPRL2 belong to the G-protein coupled seven transmembrane receptor (GPCR) family sensitive to pertussis toxin. FPR and FPRL1 were first detected in phagocytic leukocytes, and FPRL2 was found in monocytes and in dendritic cells. The three receptors were subsequently identified in other cell types or tissues, including neuronal cells and brain, where FPR and FPRL1 play a key role in angiogenesis, cell proliferation, protection against and cell death, as well as in neuroendocrine functions. Binding of different agonists to FPRs triggers several signaling pathways, activates NFkB and STAT3 transcriptional factors and induces the accumulation of the CDK inhibitors p21(waf1/cip1), p16(INK4) and p27(kip1). Signaling molecules, such as ERKs, JNK, PKC, p38MAPK, PLC and PLD are involved in these intracellular cascades. In this article we briefly review FPRs expression and signaling in neuronal cells.

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“…HEK293 cells, which express a NADPH oxidase-like enzyme, but not formyl peptide receptors, transiently transfected with FPR2 cDNA generate superoxide on stimulation with WKYMVm, demonstrating that FPR2 is a biologically functional receptor in these cells [126]. NADPH oxidase-dependent superoxide generation by WKYMVm in IMR90 cells requires also the activation of PKCα and PKCδ which translocate from the cytosolic to the membrane fraction upon stimulation with the hexapeptide [127] (Scheme 3). In human lung cancer CaLu-6 cells, stimulation with WKYMVm induces EGFR tyrosine phosphorylation, p47 phox phosphorylation, NADPH-oxidase-dependent superoxide generation and c-Src kinase activity (Scheme 4).…”

Section: Ligands From Peptide Librarymentioning

confidence: 99%

Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists

Cattaneo

Parisi

Ammendola

2013

IJMS

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The formyl peptide receptor 2 (FPR2) is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR) family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ)-42 and prion protein (Prp)106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP)-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent signal transduction pathways, including activation of phospholipase C (PLC), protein kinase C (PKC) isoforms, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, the mitogen-activated protein kinase (MAPK) pathway, p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine kinase receptor transactivation, phosphorylation and nuclear translocation of regulatory transcriptional factors, release of calcium and production of oxidants. FPR2 is an attractive therapeutic target, because of its involvement in a range of normal physiological processes and pathological diseases. Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2 agonists.

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Protein kinase C-α and -δ are required for NADPH oxidase activation in WKYMVm-stimulated IMR90 human fibroblasts

Cited by 24 publications

References 51 publications

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

Expression and Signaling of Formyl-Peptide Receptors in the Brain

Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists

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