Mouse anti-Human MTPN monoclonal antibody, clone 2G4

Fish have been highly exposed to radiation in freshwater systems after the Chernobyl Nuclear Power Plant (NPP) accident in 1986 and in freshwater and marine systems after the more recent Fukushima NPP accident in 2011. In the years after the accident, the radioactivity levels rapidly declined due to radioactive decay and environmental processes, but chronic lower dose exposures persisted. To gain insights into the long-term effects of environmental low dose radiation on fish ovaries development, a high-throughput transcriptomic approach including a de novo assembly was applied to different gonad phenotypes of female perch: developed gonads from reference lakes, developed/irradiated from medium contaminated lake, and both developed/irradiated and undeveloped from more highly contaminated lakes. This is the most comprehensive analysis to date of the gene responses in wildlife reproductive system to radiation. Some gene responses that were modulated in irradiated gonads were found to be involved in biological processes including cell differentiation and proliferation (ggnb2, mod5, rergl), cytoskeleton organization (k1C18, mtpn), gonad development (nell2, tcp4), lipid metabolism (ldah, at11b, nltp), reproduction (cyb5, cyp17A, ovos), DNA damage repair (wdhd1, rad51, hus1), and epigenetic mechanisms (dmap1). Identification of these genes provides a better understanding of the underlying molecular mechanisms underpinning the development of the gonad phenotypes of wild perch and how fish may respond to chronic exposure to radiation in their natural environment, though causal attribution of gene responses remains unclear in the undeveloped gonads.

Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic (beta-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic (beta-cells line INS-1832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375. We also studied the effect of this molecule on 3T3 -L1 pre-adipocytes cells demonstrating a down regulation of Mtpn and a dramatic increase of miR-375. Moreover, in the in vitro breast cancer model such as MDA-MB-231 and MCF-7 cells, 9cRA showed different effect on both Mtpn and miR-375 expression. In INS-1832/13, 3T3 -L1 pre-adipocytes and MCF-7 but not in MDA-MB-231, the effect of 9cRA on Mptn gene expression and its miR was under the control of RARs and RXRs receptors, as revealed by the exposure of these cell line to LE540 or HX603 receptor antagonists. In our findings 9cRA emerges has a hormone with a regulatory action on miR-375 that in most cases interfere with Mtpn expression.