Female-to-male differential transcription patterns of miRNA-mRNA networks in the livers of dioxin-exposed mice.

Non-coding microRNAs (miRNAs) have important roles in regulating the expression of liver mRNAs in response to xenobiotic-exposure, but their roles concerning dioxins such as TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin) are less clear. This report concerns the potential implication of liver (class I) and circulating (class II) miRNAs in hepatotoxicity of female and male mice after acute exposure to TCDD. The data show that, of a total of 38 types of miRNAs, the expression of eight miRNAs were upregulated in both female and male mice exposed to TCDD. Inversely, the expression of nine miRNAs were significantly downregulated in both animal genders. Moreover, certain miRNAs were preferentially induced in either females or males. The potential downstream regulatory effects of miRNAs on their target genes was evaluated by determining the expression of three group of genes that are potentially involved in cancer biogenesis, other diseases and in hepatotoxicity. It was found that certain cancer-related genes were more highly expressed females rather than males after exposure to TCDD. Furthermore, a paradoxical female-to-male transcriptional pattern was found for several disease-related and hepatotoxicity-related genes. These results suggest the possibility of developing of new miRNA-specific interfering molecules to address their dysfunctions as caused by TCDD.

Mammalian lipid droplets: structural, pathological, immunological and anti-toxicological roles.

Mammalian lipid droplets (LDs) are specialized cytosolic organelles consisting of a neutral lipid core surrounded by a membrane made up of a phospholipid monolayer and a specific population of proteins that varies according to the location and function of each LD. Over the past decade, there have been significant advances in the understanding of LD biogenesis and functions. LDs are now recognized as dynamic organelles that participate in many aspects of cellular homeostasis plus other vital functions. LD biogenesis is a complex, highly-regulated process with assembly occurring on the endoplasmic reticulum although aspects of the underpinning molecular mechanisms remain elusive. For example, it is unclear how many enzymes participate in the biosynthesis of the neutral lipid components of LDs and how this process is coordinated in response to different metabolic cues to promote or suppress LD formation and turnover. In addition to enzymes involved in the biosynthesis of neutral lipids, various scaffolding proteins play roles in coordinating LD formation. Despite their lack of ultrastructural diversity, LDs in different mammalian cell types are involved in a wide range of biological functions. These include roles in membrane homeostasis, regulation of hypoxia, neoplastic inflammatory responses, cellular oxidative status, lipid peroxidation, and protection against potentially toxic intracellular fatty acids and lipophilic xenobiotics. Herein, the roles of mammalian LDs and their associated proteins are reviewed with a particular focus on their roles in pathological, immunological and anti-toxicological processes.

Involvement of hepatic lipid droplets and their associated proteins in the detoxification of aflatoxin B1 in aflatoxin-resistance BALB/C mouse.

The highly potent carcinogen, Aflatoxin B1, induces liver cancer in many animals including humans but some mice strains are highly resistant. This murine resistance is due to a rapid detoxification of AFB1. Hepatic lipid droplets (LDs) ultimately impact the liver functions but their potential role in AFB1 detoxification has not been addressed. This study describes the structural and functional impacts on hepatic LDs in BALB/C mice after exposure to 44 (low dose) or 663 (high dose) µg AFB1/kg of body weight. After 7 days, the liver of AFB1-dosed mice did not accumulate any detectable AFB1 or its metabolites and this was associated with a net increase in gene transcripts of the AhR-mediating pathway. Of particular interest, the livers of high-dose mice accumulated many more LDs than those of low-dose mice. This was accompanied with a net increase in transcript levels of LD-associated protein-encoding genes including Plin2, Plin3 and Cideb and an alteration in the LDs lipid profiles that could be likely due to the induction of lipoxygenase and cyclooxygenase genes. Interestingly, our data suggest that hepatic LDs catalyze the in vitro activation of AFB1 into AFB1-exo-8,9-epoxide and subsequent hydrolysis of this epoxide into its corresponding dihydrodiol. Finally, transcript levels of CYP1A2, CYP1B1, GSTA3 and EH1 genes were elevated in livers of high-dose mice. These data suggest new roles for hepatic LDs in the trapping and detoxifying of aflatoxins.

Sequencing and Gene Expression Analysis of Leishmania tropica LACK Gene.

BACKGROUND: Leishmania Homologue of receptors for Activated C Kinase (LACK) antigen is a 36-kDa protein, which provokes a very early immune response against Leishmania infection. There are several reports on the expression of LACK through different life-cycle stages of genus Leishmania, but only a few of them have focused on L.tropica. METHODS: The present study provides details of the cloning, DNA sequencing and gene expression of LACK in this parasite species. First, several local isolates of Leishmania parasites were typed in our laboratory using PCR technique to verify of Leishmania parasite species. After that, LACK gene was amplified and cloned into a vector for sequencing. Finally, the expression of this molecule in logarithmic and stationary growth phase promastigotes, as well as in amastigotes, was evaluated by Reverse Transcription-PCR (RT-PCR) technique. RESULTS: The typing result confirmed that all our local isolates belong to L.tropica. LACK gene sequence was determined and high similarity was observed with the sequences of other Leishmania species. Furthermore, the expression of LACK gene in both promastigotes and amastigotes forms was confirmed. CONCLUSION: Overall, the data set the stage for future studies of the properties and immune role of LACK gene products.