Critical Roles of Thioredoxin in Nerve Growth Factor-Mediated Signal Transduction and Neurite Outgrowth in PC12 Cells

Bai, Jie; Nakamura, Hajime; Kwon, Yong-Won; Hattori, Itaro; Yamaguchi, Yoshimi; Kim, Yong-Chul; Kondo, Norihiko; Oka, Shinichi; Ueda, Shugo; Masutani, Hiroshi; Yodoi, Junji

doi:10.1523/jneurosci.23-02-00503.2003

Cited by 105 publications

(76 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Trx promoter region contains several conserved sequences for transcription factors such as the oxidative stress responsive element (ORE) (Taniguchi et al, 1996), antioxidant responsive element (ARE) (Kim et al, 2001), and the cAMP responsive element (Bai et al, 2003). ORE is thought to be not directly involved in GGA-mediated Trx induction, because N-acetylcysteine, a potent antioxidant, had no effect on GGA- mediated Trx induction (Hirota et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…These neurotrophic factors confer cytoprotection against light-induced photoreceptor cell damage (LaVail et al, 1992;Cao et al, 2001). Trx is essential for the NGF-mediated neurite outgrowth in neuronal PC12 cells (Bai et al, 2003). Trx induced in the RPE contributes to cytoprotection against ischemia-reperfusion injury of the inner retina in rats (Yamamoto et al, 1997b).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Tanito¹,

Kwon²,

Kondo³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 μm) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nm) attenuated H2O2(200 μm)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2(50 μm)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Tanito¹,

Kwon²,

Kondo³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…It has two cysteines located in its catalytic center, and it functions as a redox regulator in cells [31,32]. Earlier studies have reported that human Trx1 is readily S-nitrosylated both in vitro and in vivo, and the NO group in S-nitrosylated Trx1 can be transferred to other proteins, such as caspase-3 (at Cys163) [33] via a process called trans-nitrosylation.…”

Section: Identification Of An S-nitrosylation Site In Thioredoxinmentioning

confidence: 99%

A strategy for direct identification of protein S-nitrosylation sites by quadrupole time-of-flight mass spectrometry

Wang

Liu

et al. 2008

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

S-nitrosylation of proteins serves an important role in regulating diverse cellular processes including signal transduction, DNA repair, and neurotransmission. Identification of Snitrosylation sites is crucial for understanding the significance of this post-translational modification (PTM) in modulating the function of a protein. However, it is challenging to identify S-nitrosylation sites directly by mass spectrometric (MS) methods due to the labile nature of the 5-NO bond. Here we describe a strategy for direct identification of protein S-nitrosylation sites in an electrospray ionization (ESI) quadrupole time-of-flight (QTOF) mass spectrometer without prior chemical derivatization of S-nitrosylated peptides. Both sample buffer composition and MS hardware parameters were carefully adjusted to ensure that S-nitrosylated peptide ions could be analyzed by the QTOF MS with optimal signal/noise ratios. It was crucial that the proteins were preserved in a sample solution containing 1 mM EDTA and 0.1 mM neocuproine at neutral pH. Proteins dissolved in this solution are amenable to in-solution tryptic digestion, which is important for the analysis of biological samples. S-nitrosylated peptides were effectively analyzed by LC/MS/MS on QTOF MS, with an optimized cone voltage of 20 V and collision energy of 4 V. We have successfully applied this method to thioredoxin, a key antioxidant protein, and identified within it an S-nitrosylation site at

show abstract

“…In general, the stimuli that promote Trx expression are also capable of promoting its intracellular movement (Bai et al, 2003;Watson et al, 2003). We herein investigated if activation of PPAR␣ could induce Trx translocation from cytosol to nucleus.…”

Section: Ppar␣ Induces the Translocation Of Trx To Nucleusmentioning

confidence: 99%

“…Trx is a cytosolic protein and shuttles between cytoplasm and nucleus under many circumstances (Bai et al, 2003;Watson et al, 2003). To study the potential intranuclear effect of Trx on regulation of PPAR␣ transcriptional activity, a possible way is to deliberately in- crease nucleus-localized Trx.…”

Section: Down-regulation Of Ppar␣ Transcriptional Activity By Ectopicmentioning

confidence: 99%

Thioredoxin-mediated Negative Autoregulation of Peroxisome Proliferator-activated Receptor α Transcriptional Activity

Liu

Shen

2006

MBoC

View full text Add to dashboard Cite

PPAR␣, a member of the nuclear receptor superfamily, and thioredoxin, a critical redox-regulator in cells, were found to form a negative feedback loop, which autoregulates transcriptional activity of PPAR␣. Thioredoxin was identified as a target gene of PPAR␣. Activation of PPAR␣ leads to increase of thioredoxin expression as well as its translocation from cytoplasm to nucleus, whereas ectopic overexpression of thioredoxin in the nucleus dramatically inhibited both constitutive and ligand-dependent PPAR␣ activation. As PPAR␣-target genes, the expression of muscle carnitine palmitoyltransferase I, medium chain acyl CoA dehydrogenase, and apolipoprotein A-I were significantly down-regulated by nucleus-targeted thioredoxin at transcriptional or protein level. The suppression of PPAR␣ transcriptional activity by Trx could be enhanced by overexpression of thioredoxin reductase or knockdown of thioredoxin-interacting protein, but abrogated by mutating the redox-active sites of thioredoxin. Mammalian one-hybrid assays showed that thioredoxin inhibited PPAR␣ activity by modulating its AF-1 transactivation domain. It was also demonstrated by electrophoretic mobility-shift assay that thioredoxin inhibited the binding of PPAR␣ to the PPAR-response element. Together, it is speculated that the reported negative-feedback loop may be essential for maintaining the homeostasis of PPAR␣ activity. INTRODUCTIONAs the first identified genetic sensor for fats, PPAR␣ is a ligandactivated transcription factor belonging to the nuclear receptor superfamily. The target genes of PPAR␣ are relatively homogenous group of genes that participate in various aspects of lipid catabolism such as fatty acid uptake through membranes, fatty acid binding in cells, fatty acid oxidation in microsomes, peroxisomes and mitochondria, and lipoprotein assembly and transportation (Lemberger et al., 1996). The significance of PPAR␣ in physiology and disease is evidenced by the fact that it and PPAR␥, another subtype of PPARs, are molecular targets for the lipid-lowering fibrate drugs and insulin-sensitizing thiazolidinedione (TZD), respectively (Evans et al., 2004). Besides activation of PPAR␣ by fatty acid and various exogenous ligands such as fibrates, the regulation of the PPAR␣ transcription activity by coactivators (Dowell et al., 1997), corepressors (Dowell et al., 1999), other transcription factors (TFs; Zhou et al., 1999), and posttranslational modifications including phosphorylation (Juge-Aubry et al., 1999) and ubiquination (Blanquart et al., 2002) have been extensively studied. However, redox regulation of PPAR␣ activity has not been reported so far.Multicellular organisms have evolved complex homeostatic mechanisms to sense and respond to a diverse range of exogenous and endogenous signals. It may be reasonable to expect some mechanisms that rapidly sense and tightly control the activity of PPAR␣ according to metabolic needs under normal physiological condition. Degradation of PPAR␣ by the ubiquitin-proteasome system and decrease of the ubiquitinat...

show abstract

Critical Roles of Thioredoxin in Nerve Growth Factor-Mediated Signal Transduction and Neurite Outgrowth in PC12 Cells

Cited by 105 publications

References 51 publications

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

A strategy for direct identification of protein S-nitrosylation sites by quadrupole time-of-flight mass spectrometry

Thioredoxin-mediated Negative Autoregulation of Peroxisome Proliferator-activated Receptor α Transcriptional Activity

Contact Info

Product

Resources

About