Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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.

SUBMITTER: Jung MK

PROVIDER: S-EPMC8383465 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Taurine transporter (TauT) deficiency impairs ammonia detoxification in mouse liver.

Project description:Hepatic ammonia handling was analyzed in taurine transporter (TauT) KO mice. Surprisingly, hyperammonemia was present at an age of 3 and 12 months despite normal tissue integrity. This was accompanied by cerebral RNA oxidation. As shown in liver perfusion experiments, glutamine production from ammonia was diminished in TauT KO mice, whereas urea production was not affected. In livers from 3-month-old TauT KO mice protein expression and activity of glutamine synthetase (GS) were unaffected, whereas the ammonia-transporting RhBG protein was down-regulated by about 50%. Double reciprocal plot analysis of glutamine synthesis versus perivenous ammonia concentration revealed that TauT KO had no effect on the capacity of glutamine formation in 3-month-old mice, but doubled the ammonia concentration required for half-maximal glutamine synthesis. Since hepatic RhBG expression is restricted to GS-expressing hepatocytes, the findings suggest that an impaired ammonia transport into these cells impairs glutamine synthesis. In livers from 12-, but not 3-month-old TauT KO mice, RhBG expression was not affected, surrogate markers for oxidative stress were strongly up-regulated, and GS activity was decreased by 40% due to an inactivating tyrosine nitration. This was also reflected by kinetic analyses in perfused liver, which showed a decreased glutamine synthesizing capacity by 43% and a largely unaffected ammonia concentration dependence. It is concluded that TauT deficiency triggers hyperammonemia through impaired hepatic glutamine synthesis due to an impaired ammonia transport via RhBG at 3 months and a tyrosine nitration-dependent inactivation of GS in 12-month-old TauT KO mice.

| S-EPMC6442586 | biostudies-literature

Taurine and its transporter TAUT positively affect male reproduction and early embryo development.

Project description: Not available

| S-EPMC9156853 | biostudies-literature

Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts.

Project description:The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na(+) concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.

| S-EPMC3298736 | biostudies-literature

HSF1 Mouse Fibroblast Heat Shock - Scanner7

Project description:Mouse HSF1+/+ and HSF1-/- Fibroblasts Heat Shock Time Courses Scanned on Scanner 7 (Axon 4000B) Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set

2005-08-05 | GSE3074 | GEO

Transcriptional regulation of small heat shock protein genes by heat shock factor 1 (HSF1) in Liriomyza trifolii under heat stress.

Project description:Small heat shock proteins (sHSPs) function as molecular chaperones in multiple physiological processes and are active during thermal stress. sHSP expression is controlled by heat shock transcription factor (HSF); however, few studies have been conducted on HSF in agricultural pests. Liriomyza trifolii is an introduced insect pest of horticultural and vegetable crops in China. In this study, the master regulator, HSF1, was cloned and characterized from L. trifolii, and the expression levels of HSF1 and five sHSPs were studied during heat stress. HSF1 expression in L. trifolii generally decreased with rising temperatures, whereas expression of the five sHSPs showed an increasing trend that correlated with elevated temperatures. All five sHSPs and HSF1 showed an upward trend in expression with exposure to 40 ℃ without a recovery period. When a recovery period was incorporated after thermal stress, the expression patterns of HSF1 and sHSPs in L. trifolii exposed to 40 °C was significantly lower than expression with no recovery period. To elucidate potential interactions between HSF1 and sHSPs, double-stranded RNA was synthesized to knock down HSF1 in L. trifolii by RNA interference. The knockdown of HSF1 by RNAi decreased the survival rate and expression of HSP19.5, HSP20.8, and HSP21.3 during high-temperature stress. This study expands our understanding of HSF1-regulated gene expression in L. trifolii exposed to heat stress.

| S-EPMC8492843 | biostudies-literature

Heat shock factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response.

Project description:Despite its pivotal roles in biology, how the transcriptional activity of c-MYC is tuned quantitatively remains poorly defined. Here, we show that heat shock factor 1 (HSF1), the master transcriptional regulator of the heat shock response, acts as a prime modifier of the c-MYC-mediated transcription. HSF1 deficiency diminishes c-MYC DNA binding and dampens its transcriptional activity genome wide. Mechanistically, c-MYC, MAX, and HSF1 assemble into a transcription factor complex on genomic DNAs, and surprisingly, the DNA binding of HSF1 is dispensable. Instead, HSF1 physically recruits the histone acetyltransferase general control nonderepressible 5 (GCN5), promoting histone acetylation and augmenting c-MYC transcriptional activity. Thus, we find that HSF1 specifically potentiates the c-MYC-mediated transcription, discrete from its canonical role in countering proteotoxic stress. Importantly, this mechanism of action engenders two distinct c-MYC activation states, primary and advanced, which may be important to accommodate diverse physiological and pathological conditions.

| S-EPMC10592515 | biostudies-literature

HSF1 and HSF3 cooperatively regulate the heat shock response in lizards.

Project description:Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs.

| S-EPMC5501597 | biostudies-literature

Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival.

Project description:Heat shock factor 1 (HSF1) mediates the cellular response to stress to increase the production of heat shock protein (HSP) chaperones for proper protein folding, trafficking, and degradation; failure of this homeostatic mechanism likely contributes to neurodegeneration. We show that the neuroprotective drug riluzole increased the amount of HSF1 in NG108-15 neuroprogenitor cells by slowing the specific turnover of HSF1 and supporting a more robust and sustained activation of HSF1. Using Hsp70-luciferase as a functional readout of the activity of HSF1, we show that riluzole amplified the heat shock induction of the reporter gene with an optimal increase at 1 ?M. Immunocytochemical staining and Western blot quantitation of HSP70 in NG108-15 neuroprogenitor cells and embryonic spinal cord neurons provided corroborative evidence that riluzole amplified the HSF1-dependent regulation of HSP70 expression. Parallel studies on the GLT1 glutamate transporter showed that riluzole increased GLT1-reporter and GLT1 protein expression and that the increase was enhanced by heat shock and coincident with the increased expression of HSP70 and HSP90. This result is consistent with the anti-glutamatergic profile of riluzole and the presence of multiple heat shock elements on the GLT1 gene promoter, suggesting that riluzole may modulate GLT1 expression through HSF1. The increased HSP chaperones and GLT1 transporter blunted glutamate-induced and N-methyl D-aspartate receptor-mediated excitotoxic death. In summary, we show that riluzole increased the amount and activity of HSF1 to boost the expression of HSPs and GLT1 for neuroprotection under stress.

| S-EPMC3024774 | biostudies-literature

RNA-seq of HSF1 phase separation in heat shock and non-heat shock cells.

Project description:We investigated whether interfering with HSF1 LLPS affected the expression of its target genes using RNA sequencing. We found HS induced HSPs gene expression in LLPS-dependent manner. LLPS-dependent gene activation was also observed in M1 cells under NHS condition. In addition, LLPS-incompetent M3 infected cells showed less HSP gene expression even under HS condition. Thus, these data collectively support a crucial role for LLPS of HSF1 in activating HSP genes expression.

2021-12-19 | GSE191134 | GEO

HSF1Base: A Comprehensive Database of HSF1 (Heat Shock Factor 1) Target Genes.

Project description:HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist the refolding or degradation of damaged intracellular proteins. Accumulating evidence reveals however that HSF1 participates in several other physiological and pathological processes such as differentiation, immune response, and multidrug resistance, as well as in ageing, neurodegenerative demise, and cancer. To address how HSF1 controls these processes one should systematically analyze its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analyzing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and the Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodeling, ribosome biogenesis, and ageing. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR.

| S-EPMC6888953 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data