17β-Estradiol modulates huntingtin levels in rat tissues and in human neuroblastoma cell line.
17β-Estradiol (E2) exerts neurotrophic and neuroprotective functions in the brain. Here, E2-induced increased levels of huntingtin (HTT), a protein involved in several crucial neuronal functions is reported. E2 physiological concentrations up-regulate HTT in hippocampus and striatum of rats as well as in human neuroblastoma cells. This effect requires both nuclear and extra-nuclear estrogen receptor (ER)α activities. Intriguingly, HTT silencing completely prevents E2 protective effects against oxidative stress injury. In conclusion, these data indicate for the first time that HTT is an E2-inducible protein involved in the first steps of E2-induced signaling pathways committed to neuronal protection against oxidative stress.
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
Maria Teresa
MT
Nuzzo
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
Marco
M
Fiocchetti
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
Michela
M
Servadio
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy.
Viviana
V
Trezza
Interdepartmental Laboratory of Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, I-00146 Roma, Italy.
Paolo
P
Ascenzi
Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, I-00146 Roma, Italy. Electronic address: maria.marino@uniroma3.it.
Maria
M
Marino
D000818:Animals; D045744:Cell Line, Tumor; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D020868:Gene Silencing; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar
C086055:HTT protein, human; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D004958:Estradiol
17-β-Estradiol; Estrogen receptor α; Human neuroblastoma cells; Huntingtin; Neuroglobin