Regulation of nitric oxide production in snail (<i>Lymnaea stagnalis</i>) defence cells: a role for PKC and ERK signalling pathways

Wright, Bernice; Lacchini, Audrey H.; Davies, Angela J.; Walker, Anthony J.

doi:10.1042/bc20050066

Cited by 65 publications

(61 citation statements)

References 49 publications

(96 reference statements)

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“…This was unexpected given the involvement of PKC in both PMA-and laminarininduced H 2 O 2 release by L. stagnalis hemocytes [20] as well as in vertebrate cells as described previously [21]. In addition, the importance of PKC in a variety of molluscan immune-related functions has become increasingly apparent in recent years [23,24]. Perhaps the task PKC carries out in PMA-induced H 2 O 2 release is achieved by a different signaling protein(s) such as PI 3 K or PLA 2 in the BSA-gal induced pathway.…”

Section: Discussionmentioning

confidence: 92%

Regulation of hydrogen peroxide release in circulating hemocytes of the planorbid snail Biomphalaria glabrata

Humphries

Yoshino

2008

Developmental & Comparative Immunology

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Biomphalaria spp. serve as obligate intermediate hosts for the human blood fluke Schistosoma mansoni. Following S. mansoni penetration of Biomphalaria glabrata, hemocytes of resistant snails migrate towards the parasite, encasing the larva in a multicellular capsule resulting in its destruction via a cytotoxic reaction. Recent studies have revealed the importance of hydrogen peroxide and nitric oxide (H 2 O 2 , NO) in parasite killing [1,2]. It is assumed H 2 O 2 and NO production is tightly regulated although the specific molecules involved remain largely unknown. Consequently, the potential role of cell signaling pathways in B. glabrata hemocyte H 2 O 2 production was investigated by evaluating the effects of specific inhibitors of selected signaling proteins. Results suggest that both ERK and p38 MAPKs are involved in the regulation of B. glabrata H 2 O 2 release in response to stimulation by PMA and galactose-conjugated BSA. However, the involvement of the signaling proteins PKC, PI 3 kinase and PLA 2 differs between PMA-and BSA-gal-induced H 2 O 2 production.

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Section: Discussionmentioning

confidence: 92%

Regulation of hydrogen peroxide release in circulating hemocytes of the planorbid snail Biomphalaria glabrata

Humphries

Yoshino

2008

Developmental & Comparative Immunology

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“…Work in our laboratory has led to the detection of PKC-like proteins in L. stagnalis haemocytes and has shown that PKC phosphorylation and activation are modulated following LPS challenge (Walker and Plows, 2003). Further research also showed that PKC and ERK play a role in phagocytosis (Plows et al, 2004) and the production of nitric oxide (NO) (Wright et al, 2006) by L. stagnalis haemocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Laminarin is an oligomeric ␤-1, 3-glucan that contains ␤-1, 6-interstrand linkages; occurring in brown algae, it is structurally analogous to an oligosaccharide involved in cell-cell recognition. Laminarin elicits various responses in a range of organisms; for example it activates cell signalling in plants (Klarzynski et al, 2000) and stimulates the production of NO and O 2 -by M. galloprovincialis haemocytes (Arumugam et al, 2000) and NO by L. stagnalis haemocytes (Wright et al, 2006). It is considered that, in molluscs and insects, laminarin interacts with ␤-1, 3-glucan-binding proteins on haemocytes and stimulates the NADPH oxidase pathway, a component of the respiratory burst (Söderhäll and Cerenius, 1998;Arumugam et al, 2000).…”

Section: Production Of H 2 O 2 By Laminarin-stimulated Haemocytes Ismentioning

confidence: 99%

β-1, 3-glucan modulates PKC signalling inLymnaea stagnalisdefence cells: a role for PKC in H2O2 production and downstream ERK activation

Lacchini

Davies

Mackintosh

et al. 2006

Journal of Experimental Biology

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SUMMARY Haemocytes from the gastropod snail Lymnaea stagnalis (Linnaeus)were used as a model to characterize protein kinase C (PKC) signalling events in molluscan defence cells. Challenge of freshly collected haemocytes with theβ-1, 3-glucan laminarin resulted in a transient increase in the phosphorylation of haemocyte PKC, with maximal phosphorylation (represented by a 3.5-fold increase) occurring at 10 min; this effect was blocked by the PKC inhibitor, GF109203X. Moreover, extracellular signal-regulated kinase (ERK)was found to be a downstream target of molluscan PKC, operating via a MAPK/ERK kinase (MEK)-dependent mechanism. Pharmacological inhibition of PKC phosphorylation by U-73122 and ET-18-OCH3 suggested that laminarin-dependent PKC signalling was modulated via phospholipase C(PLC); however, a role for phosphatidylinositol-3-kinase (PI-3-K) is unlikely since the PI-3-K inhibitor LY294002 was without effect. Generation of H2O2 by haemocytes in response to laminarin was also investigated. H2O2 output increased in a dose- and time-dependent manner, with 10 mg ml-1 laminarin eliciting a 9.5-fold increase in H2O2 production after 30 min. H2O2 production was significantly attenuated by the PKC inhibitors, GF109203X and Gö 6976, and by the NADPH-oxidase inhibitor,apocynin. In conclusion, these data further our understanding of PKC signalling events in molluscan haemocytes and for the first time define a role for PKC in H2O2 production by these defence cells. Given that H2O2 is an important anti-pathogen molecule, and that haemocytes play a crucial role in the elimination of invading organisms,PKC signalling in these cells is likely to be crucial to the molluscan innate defence response.

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“…In some experiments, the proteasome inhibitor Z-Leu-Leu-Leu-aldehyde (MG132; 50 μM; Merck Chemicals, Nottinghamshire, UK), the MEK1/2 inhibitor, 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126; 1-10 μM; Sigma), or vehicle control (0.1% (v/v) DMSO; Sigma) were added with or without ESPs. The inhibitor, U0126, has previously been used at these concentrations to block MEK1/2 activity in B. glabrata and Lymnaea stagnalis haemocytes, subsequently suppressing the phosphorylation (activation) of ERK (Plows et al 2004;Plows et al 2005;Wright et al 2006;Zahoor et al 2008Zahoor et al , 2009). The concentration chosen for MG132 was similar to that used by Kim et al (1999).…”

Section: Haemocytes and Haemocyte Treatmentsmentioning

confidence: 99%

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata

Zahoor

Davies²,

Kirk³

et al. 2010

Cell Stress and Chaperones

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Synthesis of heat shock proteins (HSPs) following cellular stress is a response shared by many organisms. Amongst the HSP family, the ∼70 kDa HSPs are the most evolutionarily conserved with intracellular chaperone and extracellular immunoregulatory functions. This study focused on the effects of larval excretory-secretory products (ESPs) from the parasite Schistosoma mansoni on HSP70 protein expression levels in haemocytes (defence cells) from its snail intermediate host Biomphalaria glabrata. S. mansoni larval stage ESPs are known to interfere with haemocyte physiology and behaviour. Haemocytes from two different B. glabrata strains, one which is susceptible to S. mansoni infection and one which is resistant, both showed reduced HSP70 protein levels following 1 h challenge with S. mansoni ESPs when compared to unchallenged controls; however, the reduction observed in the resistant strain was less marked. The decline in intracellular HSP70 protein persisted for at least 5 h in resistant snail haemocytes only. Furthermore, in schistosome-susceptible snails infected by S. mansoni for 35 days, haemocytes possessed approximately 70% less HSP70. The proteasome inhibitor, MG132, partially restored HSP70 protein levels in ESP-challenged haemocytes, demonstrating that the decrease in HSP70 was in part due to intracellular degradation. The extracellular signal-regulated kinase (ERK) signalling pathway appears to regulate HSP70 protein expression in these cells, as the mitogen-activated protein-ERK kinase 1/2 (MEK1/2) inhibitor, U0126, significantly reduced HSP70 protein levels. Disruption of intracellular HSP70 protein expression in B. glabrata haemocytes by S. mansoni ESPs may be a strategy employed by the parasite to manipulate the immune response of the intermediate snail host.

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Regulation of nitric oxide production in snail (Lymnaea stagnalis) defence cells: a role for PKC and ERK signalling pathways

Cited by 65 publications

References 49 publications

Regulation of hydrogen peroxide release in circulating hemocytes of the planorbid snail Biomphalaria glabrata

Regulation of hydrogen peroxide release in circulating hemocytes of the planorbid snail Biomphalaria glabrata

β-1, 3-glucan modulates PKC signalling inLymnaea stagnalisdefence cells: a role for PKC in H2O2 production and downstream ERK activation

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata

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