RT Journal Article
T1 A Caenorhabditis elegans ortholog of human selenium-binding protein 1 is a pro-aging factor protecting against selenite toxicity.
A1 Köhnlein, Karl
A1 Urban, Nadine
A1 Guerrero-Gomez, David
A1 Steinbrenner, Holger
A1 Urbanek, Pavel
A1 Priebs, Josephine
A1 Koch, Philipp
A1 Kaether, Christoph
A1 Miranda-Vizuete, Antonio
A1 Lars-Oliver, Klotz
K1 Caenorhabditis elegans
K1 Lifespan
K1 Selenium-binding protein
K1 Stress signaling
AB Human selenium-binding protein 1 (SELENBP1) was originally identified as a protein binding selenium, most likely as selenite. SELENBP1 is associated with cellular redox and thiol homeostasis in several respects, including its established role as a methanethiol oxidase that is involved in degradation of methanethiol, a methionine catabolite, generating hydrogen sulfide (H2S) and hydrogen peroxide (H2O2). As both H2S and reactive oxygen species (such as H2O2) are major regulators of Caenorhabditis elegans lifespan and stress resistance, we hypothesized that a SELENBP1 ortholog in C. elegans would likely be involved in regulating these aspects. Here we characterize Y37A1B.5, a putative selenium-binding protein 1 ortholog in C. elegans with 52% primary structure identity to human SELENBP1. While conferring resistance to toxic concentrations of selenite, Y37A1B.5 also attenuates resistance to oxidative stress and lowers C. elegans lifespan: knockdown of Y37A1B.5 using RNA interference resulted in an approx. 10% increase of C. elegans lifespan and an enhanced resistance against the redox cycler paraquat, as well as enhanced motility. Analyses of transgenic reporter strains suggest hypodermal expression and cytoplasmic localization of Y37A1B.5, whose expression decreases with worm age. We identify the transcriptional coregulator MDT-15 and transcription factor EGL-27 as regulators of Y37A1B.5 levels and show that the lifespan extending effect elicited by downregulation of Y37A1B.5 is independent of known MDT-15 interacting factors, such as DAF-16 and NHR-49. In summary, Y37A1B.5 is an ortholog of SELENBP1 that shortens C. elegans lifespan and lowers resistance against oxidative stress, while allowing for a better survival under toxic selenite concentrations.
PB Elsevier BV
YR 2019
FD 2019-09-11
LK http://hdl.handle.net/10668/14552
UL http://hdl.handle.net/10668/14552
LA en
NO Köhnlein K, Urban N, Guerrero-Gómez D, Steinbrenner H, Urbánek P, Priebs J, et al. A Caenorhabditis elegans ortholog of human selenium-binding protein 1 is a pro-aging factor protecting against selenite toxicity. Redox Biol. 2020 Jan;28:101323.
NO This research was funded by Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany) through Research Training Group “ProMoAge” (RTG 2155, to C.K. and L.O.K.) and, in early stages, by Friedrich-Schiller-Universität Jena through start-up funds to L.O.K.. We gratefully acknowledge Dr. Karol Szafranski (Core Facility Life Science Computing, Leibniz Institute on Aging, Jena) for discussion and Dr. Marco Groth (Core Facility DNA Sequencing, Leibniz Institute on Aging, Jena) for technological support.
DS RISalud
RD Apr 10, 2025