Expression of Taurine Transporter (TauT) is Modulated by Heat Shock Factor 1 (HSF1) in Motor Neurons of ALS

Mol Neurobiol (2013) 47:699710 DOI 10.1007/s12035-012-8371-9

Expression of Taurine Transporter (TauT) is Modulated by Heat Shock Factor 1 (HSF1) in Motor Neurons of ALS

Min-Kyung Jung & Ki Yoon Kim & Na-Young Lee &

Young-Sook Kang & Yu Jin Hwang & Yunha Kim &

Jung-Joon Sung & Ann McKee & Neil Kowall &

Junghee Lee & Hoon Ryu

Received: 13 September 2012 /Accepted: 29 October 2012 /Published online: 23 November 2012 # Springer Science+Business Media New York 2012

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 [3H] 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.

Keywords Taurine transporter . Heat shock factor 1 . Transcription .Taurineuptake .Amyotrophiclateralsclerosis

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by a loss of upper and lower motor neurons resulting in progressive muscle wasting and paralysis [1]. The incidence of ALS is 12/100,000/year and may be rising. The vast majority of ALS cases are sporadic, but about 510 % of cases is familial. Missense mutations of Cu/Zn...