DNA Microarray Analysis on the Genes Differentially Expressed in the Liver of the Pufferfish, Takifugu rubripes, Following an Intramuscular Administration of Tetrodotoxin

Abstract

Pufferfish accumulate tetrodotoxin (TTX) mainly in the liver and ovary. This study aims at investigating the effect of TTX accumulation in the liver of cultured specimens of torafugu Takifugu rubripes on the hepatic gene expression by microarray analysis on Day 5 after the intramuscular administration of 0.25 mg TTX/kg body weight into the caudal muscle. TTX was detected in the liver, skin and ovary in the TTX-administered individuals. The total amount of TTX accumulated in the body was 67 ± 8% of the administered dose on Day 5. Compared with the buffer-administered control group, a total of 59 genes were significantly upregulated more than two-fold in the TTX-administered group, including those encoding chymotrypsin-like elastase family member 2A, transmembrane protein 168 and Rho GTP-activating protein 29. In contrast, a total of 427 genes were downregulated by TTX administration, including those encoding elongation factor G2, R-spondin-3, nuclear receptor activator 2 and fatty acyl-CoA hydrolase precursor. In conclusion, our results demonstrate that the intramuscular administration of TTX changes the expression of hepatic genes involved in various signaling pathways.

Marine Neurotoxins’ Effects on Environmental and Human Health: An OMICS Overview

“…Microarray [34] Takifugu rubripes Modulation of the NaV kinetic. Microarray and RT-qPCR [35] Nassarius succinctus, Nassarius variciferus…”

“…Feroudj et al [34] demonstrated an upregulation of interleukin-6, known to induce the expression of APP in the liver during injury [134], and complement components such as APP. A recent study on the liver of T. rubripes was interested in dysregulated molecular pathways 5 days after intramuscular administration of TTX, analyzed by microarray and RT-qPCR [35]. APP were not able to be observed in dysregulation; however, Matsumoto et al [35] demonstrated an upregulation of 69 genes, including the sodium channel β-2 subunit gene, which modulates the kinetics of channel gating as well as the stabilization and location of TTX-sensitive NaV [135,136].…”

“…A recent study on the liver of T. rubripes was interested in dysregulated molecular pathways 5 days after intramuscular administration of TTX, analyzed by microarray and RT-qPCR [35]. APP were not able to be observed in dysregulation; however, Matsumoto et al [35] demonstrated an upregulation of 69 genes, including the sodium channel β-2 subunit gene, which modulates the kinetics of channel gating as well as the stabilization and location of TTX-sensitive NaV [135,136]. With this result, the upregulation of dysferlin may explain the damage to plasmatic membranes by TTX accumulation in the liver 5 days after exposure.…”

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

“…Some studies exploring these mechanisms have shown that when non-toxic cultured specimens of Takifugu rubripes or Takifugu niphobles are reared with a TTX-containing diet, toxins are efficiently accumulated in their livers and skin, where they are retained for a long period even after the toxic diet is stopped. Many recent studies have used high through-put profiling technologies to identify the related pattern of tetrodotoxin accumulation in pufferfish [12,13], but few have untangled the critical regulatory mechanism between the differentially expressed proteins and mRNAs during TTX transfer and accumulation in the skin [14,15]. Transcriptomics and proteomics have been used to identify important molecular mechanisms involved in various biological processes [16].…”