Blockade of protein kinase C is involved in the inhibition by cycloheterophyllin of neutrophil superoxide anion generation

Wang, J. P.; Raung, Shue L; Tsao, Lo‐Ti; Hsu, Mei‐Feng; Lin, Chun‐Nan

doi:10.1007/pl00004982

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…To evaluate this possibility, HEK293 cells were treated with PMA (phorbol 12-myristate 13-acetate) (500 nM; 60 min) to then assess changes in ligand-induced βarr2 recruitment and internalization. Activation of typical and novel PKC isoforms by the phorbol ester [42, 43] increased βarr2 recruitment (Fig. 6a) and DOR internalization (Fig.…”

Section: Resultsmentioning

confidence: 99%

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

Charfi

Nagi

Mnie-Filali

et al. 2013

Cell. Mol. Life Sci.

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Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells.

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Section: Resultsmentioning

confidence: 99%

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

Charfi

Nagi

Mnie-Filali

et al. 2013

Cell. Mol. Life Sci.

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“…heterophyllus . Previous studies have reported that cycloheterophyllin has anti-platelet, anti-oxidative, anti-inflammatory, anti-diabetic, and anti-tuberculosis activity [9–11, 23, 24]. In this study, we further investigated the molecular mechanisms and biological activities of cycloheterophyllin with a particular focus on its protective effect against UVA-induced damage and oxidative stress injury.…”

Section: Discussionmentioning

confidence: 98%

“…Cycloheterophyllin (C 30 H 30 O 7 ), a prenylflavone (Fig 1A), is isolated from Artocarpus heterophyllus , and has pharmacological and biological functions including anti-inflammatory effects, anti-platelet activities, and antioxidant properties [8–11]. However, it is unknown whether cycloheterophyllin can modulate the signaling pathways triggered by UVA in human dermal fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Photoprotective Effects of Cycloheterophyllin against UVA-Induced Damage and Oxidative Stress in Human Dermal Fibroblasts

Huang

et al. 2016

PLoS ONE

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Ultraviolet (UV) radiation, particularly ultraviolet A (UVA), is known to play a major role in photoaging of the human skin. Many studies have demonstrated that UV exposure causes the skin cells to generate reactive oxygen species and activates the mitogen-activated protein kinase (MAPK) pathway. Previous studies have also demonstrated that cycloheterophyllin has an antioxidant effect and can effectively scavenge free radicals. Extending the aforementioned investigations, in this study, human dermal fibroblasts were used to investigate the protective effect of cycloheterophyllin against UV-induced damage. We found that cycloheterophyllin not only significantly increased cell viability, but also attenuated the phosphorylation of MAPK after UVA exposure. Furthermore, cycloheterophyllin could reduce hydrogen peroxide (H2O2) generation and down-regulate H2O2-induced MAPK phosphorylation. In the in vivo studies, the topical application of cycloheterophyllin before UVA irradiation significantly decreased trans-epidermal water loss (TEWL), erythema, and blood flow rate. These results indicate that cycloheterophyllin is a photoprotective agent that inhibits UVA-induced oxidative stress and damage, and could be used in the research on and prevention of skin photoaging.

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“…Neutrophils (4 × 10 7 cells ml −1 ) were stimulated with kazinol B or phorbol 12‐myristate 13‐acetate (PMA) at 37°C, and then disrupted in Tris buffer with 1 mM EGTA and 10 μg ml −1 of leupeptin and antipain by sonication, and fractionated as previously described (Wang et al , 1997b). The cytosol and the particulate fractions were stored at −70°C until use.…”

Section: Methodsmentioning

confidence: 99%

The signal transduction mechanism involved in kazinol B‐stimulated superoxide anion generation in rat neutrophils

Wang

Tsao

Raung

et al. 1998

British J Pharmacology

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1 In this study, the underlying mechanism of stimulation of respiratory burst by kazinol B, a natural isoprenylated¯avan, in rat neutrophils in vitro was investigated. 2 Kazinol B concentration-dependently stimulated the superoxide anion (O 2 ⋅7 ) generation, with a lag but transient activation pro®le, in neutrophils but not in a cell-free system. The maximum response (13.2+1.4 nmol O 2 ⋅7 10 min 71 per 10 6 cells) was observed at 10 mM kazinol B.3 Pretreatment of neutrophils with phorbol 12-myristate 13-acetate (PMA) or formylmethionyl-leucylphenylalanine (fMLP) signi®cantly enhanced the O 2 ⋅7 generation following the subsequent stimulation of cells with kazinol B. 4 Cells pretreated with EGTA or a protein kinase inhibitor staurosporine e ectively attenuated the kazinol B-induced O 2 ⋅7 generation. However, a p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and a phosphoinositide 3-kinase (PI3K) inhibitor wortmannin had no e ect on the kazinol Binduced response. 5 Kazinol B signi®cantly stimulated [Ca 2+ ] i elevation in neutrophils, with a lag and slow rate of rise activation pro®le, and this response was attenuated by a phospholipase C (PLC) inhibitor U73122. Kazinol B also stimulated the inositol bis-and trisphosphate (IP 2 and IP 3 ) formation with a 1 min lag time. 6 The membrane-associated PKC-a and PKC-y but not PKC-i were increased following the stimulation of neutrophils with kazinol B. It was more rapid and sensitive in the activation of PKC-y than PKC-a by kazinol B. Kazinol B partially inhibited the [ 3 H]phorbol 12,13-dibutyrate ([ 3 H]PDB) binding to the neutrophil cytosolic PKC. 7 Neither the cellular mass of phosphatidic acid (PA) and phosphatidylethanol (PEt), in the presence of ethanol, nor the protein tyrosine phosphorylation were stimulated by kazinol B. In addition, the kazinol B-induced O 2 ⋅7 generation remained relatively unchanged in cells pretreated with ethanol or a tyrosine kinase inhibitor genistein. 8 Collectively, these results indicate that the stimulation of the respiratory burst by kazinol B is probably mediated by the synergism of PKC activation and [Ca 2+ ] i elevation in rat neutrophils.

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Blockade of protein kinase C is involved in the inhibition by cycloheterophyllin of neutrophil superoxide anion generation

Cited by 12 publications

References 38 publications

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

Photoprotective Effects of Cycloheterophyllin against UVA-Induced Damage and Oxidative Stress in Human Dermal Fibroblasts

The signal transduction mechanism involved in kazinol B‐stimulated superoxide anion generation in rat neutrophils

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