title: Expression of taurine transporter (TauT) is modulated by heat shock factor 1 (HSF1) in motor neurons of ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive paralysis caused by the degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 (SOD1) are a cause of familial ALS. In the present study, we demonstrated an age-dependent increase in taurine transporter (TauT) immunoreactivity in spinal cord motor neurons of ALS transgenic mice (mutant SOD1 (G93A)) and a similar increase in TauT in spinal motor neurons of patients with ALS. Chromatin immunoprecipitation analysis verified that heat shock factor 1 (HSF1) preferentially occupies the HSF1 binding element in the promoter of TauT under oxidative stress conditions. Knockdown of HSF1 by small interfering RNA reduced the transcriptional activity of TauT. Using [(3)H] taurine, we confirmed that an elevated expression of TauT directly contributes to increased taurine uptake in ALS motor neurons. In addition, we showed that taurine plays an antioxidant role and may prevent motor neuron loss due to oxidative stress in ALS. Our findings suggest that HSF1-induced TauT expression partially protects motor neurons by compensating for constitutive oxidative stress, which is thought to be a key mechanism contributing to the pathogenesis of ALS. Taken together, our results suggest that TauT is a novel pathological marker for stressed motor neurons in ALS and that modulation of TauT and taurine may slow neuronal degeneration in ALS.
authors.affiliation: WCU Neurocytomics Group, Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, South Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Jung
authors.forename: Ki Yoon
authors.initials: KY
authors.lastname: Kim
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Lee
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Kang
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Hwang
authors.forename: Yunha
authors.initials: Y
authors.lastname: Kim
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.forename: Ann
authors.initials: A
authors.lastname: McKee
authors.forename: Neil
authors.initials: N
authors.lastname: Kowall
authors.forename: Junghee
authors.initials: J
authors.lastname: Lee
authors.forename: Hoon
authors.initials: H
authors.lastname: Ryu
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D000099247:Taurine Transporters
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D014157:Transcription Factors; D000099247:Taurine Transporters; C490017:Hsf1 protein, mouse