β adrenergic receptor/cAMP/PKA signaling contributes to the intracellular Ca2+ release by tentacle extract from the jellyfish Cyanea capillata

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Intracellular Ca ²⁺ overload induced by extracellular Ca ²⁺ entry has previously been confirmed to be an important mechanism for the cardiotoxicity as well as the acute heart dysfunction induced by jellyfish venom, while the underlying mechanism remains to be elucidated.

Methods

Under extracellular Ca ²⁺-free or Ca ²⁺-containing conditions, the Ca ²⁺ fluorescence in isolated adult mouse cardiomyocytes pre-incubated with tentacle extract (TE) from the jellyfish Cyanea capillata and β blockers was scanned by laser scanning confocal microscope. Then, the cyclic adenosine monophosphate (cAMP) concentration and protein kinase A (PKA) activity in primary neonatal rat ventricular cardiomyocytes were determined by ELISA assay. Furthermore, the effect of propranolol against the cardiotoxicity of TE was evaluated in Langendorff-perfused rat hearts and intact rats.

Results

The increase of intracellular Ca ²⁺ fluorescence signal by TE was significantly attenuated and delayed when the extracellular Ca ²⁺ was removed. The β adrenergic blockers, including propranolol, atenolol and esmolol, partially inhibited the increase of intracellular Ca ²⁺ in the presence of 1.8 mM extracellular Ca ²⁺ and completely abolished the Ca ²⁺ increase under an extracellular Ca ²⁺-free condition. Both cAMP concentration and PKA activity were stimulated by TE, and were inhibited by the β adrenergic blockers. Cardiomyocyte toxicity of TE was antagonized by β adrenergic blockers and the PKA inhibitor H89. Finally, the acute heart dysfuction by TE was antagonized by propranolol in Langendorff-perfused rat hearts and intact rats.

Conclusions

Our findings indicate that β adrenergic receptor/cAMP/PKA signaling contributes to the intracellular Ca ²⁺ overload through intracellular Ca ²⁺ release by TE from the jellyfish C. capillata.

Related collections

Most cited references 45

Record: found
Abstract: found
Article: found

Is Open Access

Jellyfish Stings and Their Management: A Review

Luca Cegolon, William Heymann, John H. Lange … (2013)

Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In severe cases, the most important step is stabilizing and maintaining vital functions. With some differences between species, there seems to be evidence and consensus on oral/topical analgesics, hot water and ice packs as effective painkillers and on 30 s application of domestic vinegar (4%–6% acetic acid) to prevent further discharge of unfired nematocysts remaining on the skin. Conversely, alcohol, methylated spirits and fresh water should be carefully avoided, since they could massively discharge nematocysts; pressure immobilization bandaging should also be avoided, as laboratory studies show that it stimulates additional venom discharge from nematocysts. Most treatment approaches are presently founded on relatively weak evidence; therefore, further research (especially randomized clinical trials) is strongly recommended. Dissemination of appropriate treatment modalities should be deployed to better inform and educate those at risk. Adequate signage should be placed at beaches to notify tourists of the jellyfish risk. Swimmers in risky areas should wear protective equipment.

0 comments Cited 57 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Chironex fleckeri (box jellyfish) venom proteins: expansion of a cnidarian toxin family that elicits variable cytolytic and cardiovascular effects.

Diane L. Brinkman, Nicki Konstantakopoulos, Bernie V McInerney … (2014)

The box jellyfish Chironex fleckeri produces extremely potent and rapid-acting venom that is harmful to humans and lethal to prey. Here, we describe the characterization of two C. fleckeri venom proteins, CfTX-A (∼40 kDa) and CfTX-B (∼42 kDa), which were isolated from C. fleckeri venom using size exclusion chromatography and cation exchange chromatography. Full-length cDNA sequences encoding CfTX-A and -B and a third putative toxin, CfTX-Bt, were subsequently retrieved from a C. fleckeri tentacle cDNA library. Bioinformatic analyses revealed that the new toxins belong to a small family of potent cnidarian pore-forming toxins that includes two other C. fleckeri toxins, CfTX-1 and CfTX-2. Phylogenetic inferences from amino acid sequences of the toxin family grouped CfTX-A, -B, and -Bt in a separate clade from CfTX-1 and -2, suggesting that the C. fleckeri toxins have diversified structurally and functionally during evolution. Comparative bioactivity assays revealed that CfTX-1/2 (25 μg kg(-1)) caused profound effects on the cardiovascular system of anesthetized rats, whereas CfTX-A/B elicited only minor effects at the same dose. Conversely, the hemolytic activity of CfTX-A/B (HU50 = 5 ng ml(-1)) was at least 30 times greater than that of CfTX-1/2. Structural homology between the cubozoan toxins and insecticidal three-domain Cry toxins (δ-endotoxins) suggests that the toxins have a similar pore-forming mechanism of action involving α-helices of the N-terminal domain, whereas structural diversification among toxin members may modulate target specificity. Expansion of the cnidarian toxin family therefore provides new insights into the evolutionary diversification of box jellyfish toxins from a structural and functional perspective.

0 comments Cited 33 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni.

Yoko M. NAKAO, K Takuwa, Rafael T Nakajima … (2000)

During summer and autumn, the box jellyfish (sea wasp) Carybdea rastoni is one of the most bothersome stinging pests to swimmers and bathers on the Japanese coast. Two labile but potent hemolytic toxins from the tentacles of Carybdea rastoni were isolated in their active forms using newly developed purification methods. The molecular masses of the isolated C. rastoni toxin-A and toxin-B (CrTX-A and CrTX-B) are 43 and 46 kDa, respectively, as calculated from SDS-PAGE. In the present study, we sequenced the full-length cDNA (1600 bp), which encodes both CrTX-A and CrTX-B. The deduced 450 amino acid sequence of the CrTXs, showed no significant homology with any known protein. This report presents the first complete sequence of a proteinaceous jellyfish toxin. Furthermore, it was revealed that CrTX-A was primarily localized in the nematocyst, whereas CrTX-B was detected only in the tentacle. Because the nematocyst is the organ responsible for the cnidarian sting, the remainder of the study focused on the toxicity of CrTX-A. We found that CrTX-A was fatally toxic to mice at 20 microg/kg (i.v.) and crayfish at 5 microg/kg (i.p.). Subcutaneously injected CrTX-A (0.1 microg) caused inflammation of mouse skin. These results showed that CrTX-A is responsible for the cutaneous inflammation observed in humans stung by C. rastoni. Copyright 2000 Academic Press.

0 comments Cited 32 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Liang Xiao: +86-21-8187-1128 , hormat830713@hotmail.com

Liming Zhang:

ORCID: http://orcid.org/0000-0002-1595-2296

+86-21-8187-1128 , lmzhang@smmu.edu.cn

Journal

Journal ID (nlm-ta): BMC Pharmacol Toxicol

Journal ID (iso-abbrev): BMC Pharmacol Toxicol

Title: BMC Pharmacology & Toxicology

Publisher: BioMed Central (London )

ISSN (Electronic): 2050-6511

Publication date (Electronic): 25 July 2017

Publication date PMC-release: 25 July 2017

Publication date Collection: 2017

Volume: 18

Electronic Location Identifier: 60

Affiliations

ISNI 0000 0004 0369 1660, GRID grid.73113.37, Department of Marine Biotechnology, Faculty of Naval Medicine, , Second Military Medical University, ; Shanghai, 200433 China

Author information

Liming Zhang http://orcid.org/0000-0002-1595-2296

Article

Publisher ID: 167

DOI: 10.1186/s40360-017-0167-0

PMC ID: 5526252

PubMed ID: 28743285

SO-VID: bce84d81-aa23-48b1-8fd2-add1e2692db2

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 18 April 2017

Date accepted : 19 July 2017

Funding

Funded by: Young Scientists Fund of National Natural Science Foundation of China

Award ID: 81401578

Award Recipient : Qianqian Wang

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81370833

Award ID: 81470518

Award Recipient : Liang Xiao Liming Zhang

Custom metadata

ScienceOpen disciplines: Toxicology

Keywords: cyanea capillata,tentacle extract,β adrenergic receptor,heart dysfunction,propranolol

Data availability:

ScienceOpen disciplines: Toxicology

Keywords: cyanea capillata, tentacle extract, β adrenergic receptor, heart dysfunction, propranolol

Comments

Comment on this article

scite_

Cited by 1

Spontaneous myogenic fasciculation associated with the lengthening of cardiac muscle in response to static preloading
Authors: Shouyan Fan, Lingfeng Gao, Annie Christel Bell …

See all cited by

Most referenced authors 461

See all reference authors