title: Proteomics approach to examine the cardiotoxic effects of Nemopilema nomurai Jellyfish venom.
abstract: Nemopilema nomurai is one of the largest species of jellyfish in the world. It blooms mainly offshore of Korea, China, and Japan. Increasing population numbers of N. nomurai is increasing the risk of sea bathers to the jellyfish stings and accompanying envenomations. Cardiovascular effects, and cytotoxicity and hemolytic activities have been previously reported in rodent models. To understand the mechanism of cardiac toxicity, we examined the effect of N. nomurai jellyfish venom (NnV) at the proteome level on rat cardiomyocytes cell line H9c2 using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Cells treated with NnV displayed dose-dependent inhibition of viability. Cellular changes at proteome level were investigated after 6h and 12h of venom treatment. Electrophoretic examination revealed 72 protein spots displaying significant quantitative changes. These proteins were analyzed by MALDI-TOF/MS. Thirty four differentially expressed proteins were successfully identified; 24 proteins increased in quantity and 10 proteins decreased, compared to the respective controls. Proteins altered in content in Western blot analyses included myosin VII, annexin A2, aldose reductase, suppressor of cytokine signaling 1 (SOCS1), and calumenin, which are well-known marker proteins of cardiac dysfunctions.
  
  
  CONCLUSIONS
  This is the first report revealing the cardiac toxicity of NnV at the proteome level. NnV directly targeted proteins involved in cardiac dysfunction or maintenance. Suppressor of cytokine signaling 1 (SOCS1), which inhibits the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, was upregulated by NnV. Other proteins related to cardiac arrest that were over-expressed included aldose reductase and calumenin. These results clarify the underlying mechanism of cardiomyocyte damage caused by NnV. By inhibiting these particular targets and more precisely identifying the components of NnV-mediated cardiac toxicity, jellyfish venom-associated poisoning could be reduced or prevented.
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Indu
authors.initials: I
authors.lastname: Choudhary
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hyunkyoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Pyo
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Yunwi
authors.initials: Y
authors.lastname: Heo
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Seong Kyeong
authors.initials: SK
authors.lastname: Bae
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kwon
authors.affiliation: Headquarters for Marine Environment, National Fisheries Research & Development Institute, Shiran-ri, Gijang-eup, Gijang-gun, Busan 619-705, Republic of Korea.
authors.forename: Won Duk
authors.initials: WD
authors.lastname: Yoon
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea; Institutes of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Changkeun
authors.initials: C
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea; Institute of Animal Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea. Electronic address: ekim@gnu.ac.kr.
authors.forename: Euikyung
authors.initials: E
authors.lastname: Kim
mesh_terms: D054715:Cardiotoxins / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003064:Cnidarian Venoms / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
chemical_list: D054715:Cardiotoxins; D003064:Cnidarian Venoms; D020543:Proteome
keywords: 2DE; Jellyfish; MALDI-TOF/MS; Nemopilema nomurai; Protein; Venom