Characterization of two Caenorhabditis elegans Orthologs of Selenium-binding protein 1, associated with aging

Köhnlein, Karl GND

The selenium-binding protein 1 (SELENBP1) contains selenium probably in the form of selenite. SELENBP1 is involved in the regulation of cell proliferation and differentiation, and it is downregulated in many types of tumors. To better understand principal functions of SELENBP1 in vivo, the aim of this work was to investigate the role and the regulation of two putative SELENBP1 orthologs, Y37A1B.5 and R11G10.2, in the model organism C. elegans. Knockdown of these proteins had previously been shown to increase lifespan and stress resistance of C. elegans. In this thesis, it was demonstrated that Y37A1B.5 expression is induced by selenite. Two transcription factors, MDT 15 and EGL 27, regulated Y37A1B.5 abundance and influenced the stress resistance elicited by treatment with Y37A1B.5 RNAi. Y37A1B.5 appears to protect C. elegans from high concentrations of selenium, as treatment selenite dose-dependently increased protein levels of Y37A1B.5 and Y37A1B.5 depletion shortened the survival of worms exposed to toxic doses of selenite. In contrast to the hypodermal localization of Y37A1B.5, R11G10.2 was found exclusively in two head neurons, BAG and AFD, which are involved in the response to O2 and CO2,, in the perception of environmental temperatures as well as in lifespan regulation. It was demonstrated that depletion of R11G10.2 results in increased levels of reduced glutathione in the worms, which could contribute to the observed stress resistance upon treatment with R11G10.2 RNAi. The neuronal expression of R11G10.2 might indicate similarities to human SELENBP1, which was discussed to be important for normal brain function. In summary, this work identified several functions of the two SELENBP1 orthologs in the nematode Caenorhabditis elegans, with show similarities to the role of SELENBP1 in humans, and it elucidated molecular mechanisms underlying the observed increases in stress resistance and lifespan upon knockdown of the orthologs Y37A1B.5 and R11G10.2.

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