Multi-Omics Analysis of Gene and Protein Candidates Possibly Related to Tetrodotoxin Accumulation in the Skin of Takifugu flavidus.

Huimin Feng,Kun Qiao,Bei Chen,Hua Hao,Zhiyu Liu,Zhen Huang,Qin Wang,Chunchun Wang,Min Xu

doi:10.3390/md19110639

Abstract

Pufferfish is increasingly regarded by many as a delicacy. However, the tetrodotoxin (TTX) that accumulates in its body can be lethal upon consumption by humans. TTX is known to mainly accumulate in pufferfish skin, but the accumulation mechanisms are poorly understood. In this study, we aimed to explore the possible mechanism of TTX accumulation in the skin of the pufferfish Takifugu flavidus following treatment with TTX. Through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we detected 37.3% of toxin accumulated in the skin at the end of the rearing period (168 h). Transcriptome and proteome analyses revealed the mechanism and pathways of TTX accumulation in the skin of T. flavidus in detail. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analyses strongly suggest that cardiac muscle contraction and adrenergic signaling in cardiomyocyte pathways play an important role in TTX accumulation. Moreover, some upregulated and downregulated genes, which were determined via RNA-Seq, were verified with qPCR analysis. This study is the first to use multi-omics profiling data to identify novel regulatory network mechanisms of TTX accumulation in the skin of pufferfish.

Highlights

Introduction published maps and institutional affilPufferfish, called blowfish, refers to any of approximately 90 species of the familyTetraodontidae
TTX was orally administered via gavage to non-toxic cultured specimens of the puffTTXT.was orally administered via transfer gavage and to non-toxic cultured erfish flavidus to investigate the toxin accumulation profilesspecimens in the skin.of the pufferfish flavidus to investigate the toxin transfer and accumulation
These findings show that TTX is transferred mainly to the liver flavidus following short-term administration, and that TTX can accumulate in the skin of T

Summary

Introduction

Introduction published maps and institutional affilPufferfish, called blowfish, refers to any of approximately 90 species of the familyTetraodontidae. Pufferfish, called blowfish, refers to any of approximately 90 species of the family. It is common knowledge that pufferfish inflate themselves with air or water into a spherical shape. Puffers are primarily found in the sea and, in some instances, in brackish water or freshwater [1]. Pufferfish are sometimes used as food and have long been regarded as one of the most delicious fish in Japan. Many pufferfish possess a potent neurotoxin, tetrodotoxin (TTX), which is especially concentrated in the internal organs. The liver and ovary are highly toxic in general, whereas in brackish water and freshwater species, toxicity is higher in the skin

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