PMID- 28526336 OWN - NLM STAT- MEDLINE DCOM- 20180706 LR - 20181202 IS - 1879-3150 (Electronic) IS - 0041-0101 (Linking) VI - 133 DP - 2017 Jul TI - Activation of Na(+)/H(+) exchanger other than formation of transmembrane pore underlies the cytotoxicity of nematocyst venom from Chrysaora helvola Brandt jellyfish. PG - 162-168 LID - S0041-0101(17)30154-X [pii] LID - 10.1016/j.toxicon.2017.05.016 [doi] AB - We previously reported unexpected apoptosis-like cell death induced by nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish. To assess whether the pore formation mechanism underlay the action of NV, the change in cell membrane permeability was studied in both chicken erythrocytes and human CNE-2 cells. Initially, paradoxical results were derived from osmoprotectant protection assays. Polyethylene glycol (PEG)(2000), which completely inhibited the NV induced hemolysis, failed to protect CNE-2 cells. Detailed experiments showed that PEG protection from hemolysis is concentration dependent and indicated caution when estimating the pore size formed by NV with the osmotic protection method. NV-treated CNE-2 cells remained impermeable to dyes with various molecular weights (MWs) (622.6-40,000 Da). Furthermore, membrane depolarization and selective permeability to Na(+) other than K(+) were induced in CNE-2 cells. No oxidative damage to the cell membrane was detected. Amiloride, an inhibitor of Na(+)/H(+) exchanger (NHE), substantially protected both CNE-2 cells and erythrocytes from NV. Combined with the previously reported increase in intracellular pH, we supposed that NV activated plasma membrane NHE without forming transmembrane pores. Interestingly, glutathione (GSH) showed significant protection to CNE-2 cells while potentiating the hemolytic power of NV. This finding may suggest a key role of reactive oxygen species (ROS) in the cytotoxicity of NV. To the best of our knowledge, this is the first report that a hemolytic jellyfish venom acts through NHE in a manner other than compromising membrane integrity. The current work provides new insight into the arsenal of toxic jellyfishes. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Fan, Lanlan AU - Fan L AD - School of Pharmacy, Guangxi University of Chinese Medicine, 530001, Nanning, China. FAU - Luo, Jun AU - Luo J AD - School of Pharmacy, Guangxi University of Chinese Medicine, 530001, Nanning, China. FAU - Li, Xiaoyong AU - Li X AD - National Engineering Laboratory of Southwest Endangered Medicinal Resources Development, Guangxi Botanical Garden of Medicinal Plants, 530023, Nanning, China. FAU - Chen, Ming AU - Chen M AD - State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 541004, Guilin, China. FAU - Shu, Wei AU - Shu W AD - Department of Cell Biology & Genetics, Guangxi Medicinal University, Nanning, 530021, China. FAU - Qu, Xiaosheng AU - Qu X AD - National Engineering Laboratory of Southwest Endangered Medicinal Resources Development, Guangxi Botanical Garden of Medicinal Plants, 530023, Nanning, China. Electronic address: 239653129@qq.com. LA - eng PT - Journal Article DEP - 20170517 PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Cnidarian Venoms) RN - 0 (Sodium-Hydrogen Exchangers) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Membrane Permeability MH - Chickens MH - Cnidarian Venoms/*toxicity MH - Glutathione/metabolism MH - Hemolysis MH - Humans MH - Polyethylene Glycols MH - *Scyphozoa MH - Sodium-Hydrogen Exchangers/*metabolism OTO - NOTNLM OT - Chrysaora helvola Brandt OT - Glutathione OT - Na(+) influx OT - Na(+)/H(+) exchanger OT - Nematocyst venom OT - Permeability EDAT- 2017/05/21 06:00 MHDA- 2018/07/07 06:00 CRDT- 2017/05/21 06:00 PHST- 2016/11/19 00:00 [received] PHST- 2017/04/25 00:00 [revised] PHST- 2017/05/15 00:00 [accepted] PHST- 2017/05/21 06:00 [pubmed] PHST- 2018/07/07 06:00 [medline] PHST- 2017/05/21 06:00 [entrez] AID - S0041-0101(17)30154-X [pii] AID - 10.1016/j.toxicon.2017.05.016 [doi] PST - ppublish SO - Toxicon. 2017 Jul;133:162-168. doi: 10.1016/j.toxicon.2017.05.016. Epub 2017 May 17.