Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

Major histocompatibility complex class I involvement in the rejection of allogeneic erythrocytes in rainbow trout (Oncorhynchus mykiss)

Major histocompatibility complex genes are thought to be involved in allogeneic graft rejection but not many reports are available on their functional analysis in fish. Analysis of available sequences of MHC genes suggests functions in antigen presentation similar to those found in higher vertebrates. In mammals, the MHC class I and class II molecules are major determinants of allogeneic graft rejection due to their polymorphism in conjunction with their antigen presenting function. In fish, MHC class H molecules are found to be involved in rejection of allogeneic scale grafts. The present study was designed to investigate the involvement of MHC class I molecules in allograft rejection. Erythrocytes were collected from donors of rainbow trout expressed different class MHC class I alleles, stained with two dyes, mixed and grafted to the recipients that were of the same sibling group as the donors. The grafts were rejected by allogeneic recipients and the MHC class I linkage group was the major determinant for the rejection.