Thioredoxin from Activated Macrophages as a Trophic Factor for Central Cholinergic Neurons in Vitro

doi:10.1006/bbrc.1993.1479

Biochemical and Biophysical Research Communications

Volume 192, Issue 2, 30 April 1993, Pages 760-765

https://doi.org/10.1006/bbrc.1993.1479 Get rights and content

Abstract

The conditioned medium from γ-interferon-stimulated rnacrophages elevated the choline acetyltransferase activity in mouse septal neurons as well as in cholinergic hybrid cell lines SN6.10.2.2 in vitro. After purification and sequencing, the active fraction was identical to thioredoxin (TRX), and the neurotrophic activity of recombinant TRX was confirmed.

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Cited by (34)

Role of Thioredoxin-1 and its inducers in human health and diseases
2022, European Journal of Pharmacology
Citation Excerpt :
Nevertheless, the exact mechanism by which panaxatriol saponin inhibit MPTP-mediated neuronal death in the substantia nigra pars compacta by increasing Trx-1 expression is not clear. It may be because Trx-1 is a neurotrophic factor for central cholinergic neurons and plays a key role in nerve growth factor-mediated signal transduction and neurite growth (Endoh et al., 1993; Bai et al., 2003). Consequently, panaxatriol saponin may protect dopaminergic neurons by regulating neurotrophic factor-mediated signaling through the induction of Trx-1 expression.
Thioredoxin-1 (Trx-1) is a small redox-active protein normally found in mammalian cells that responds to the changing redox environment by contributing electrons or regulating related proteins. There is growing evidence that Trx-1 has multiple functions, including cytoprotective, anti-apoptotic, antioxidant and anti-inflammatory effects. To date, researchers have found that Trx-1 deficiency leads to severe damage in various disease models, such as atherosclerosis, cerebral ischemia, diabetes and tumors. Conversely, activation of Trx-1 has a protective effect against these diseases. Accordingly, a variety of Trx-1 inducers have been widely used in the clinic with significant therapeutic value. In this paper, we summarize the pathogenesis of Trx-1 involvement in the above-mentioned diseases and describe the protective effects of Trx-1 inducers on them.
More than a syllable in fib-ROS-is: The role of ROS on the fibrotic extracellular matrix and on cellular contacts
2018, Molecular Aspects of Medicine
Fibrosis is characterized by excess deposition of extracellular matrix (ECM). However, the ECM changes during fibrosis not only quantitatively but also qualitatively. Thus, the composition is altered as the expression of various ECM proteins changes. Moreover, also posttranslational modifications, secretion, deposition and crosslinkage as well as the proteolytic degradation of ECM components run differently during fibrosis. As several of these processes involve redox reactions and some of them are even redox-regulated, reactive oxygen species (ROS) influence fibrotic diseases. Redox regulation of the ECM has not been studied intensively, although evidences exist that the alteration of the ECM, including the redox-relevant processes of its formation and degradation, may be of key importance not only as a cause but also as a consequence of fibrotic diseases. Myofibroblasts, which have differentiated from fibroblasts during fibrosis, produce most of the ECM components and in return obtain important environmental cues of the ECM, including their redox-dependent fibrotic alterations. Thus, myofibroblast differentiation and fibrotic changes of the ECM are interdependent processes and linked with each other via cell-matrix contacts, which are mediated by integrins and other cell adhesion molecules. These cell-matrix contacts are also regulated by redox processes and by ROS. However, most of the redox-catalyzing enzymes are localized within cells. Little is known about redox-regulating enzymes, especially the ones that control the formation and cleavage of redox-sensitive disulfide bridges within the extracellular space. They are also important players in the redox-regulative crosstalk between ECM and cells during fibrosis.
Sex- and structure-specific differences in antioxidant responses to methylmercury during early development
2016, NeuroToxicology
Methylmercury (MeHg) is a ubiquitous environmental contaminant and neurotoxin, particularly hazardous to developing and young individuals. MeHg neurotoxicity during early development has been shown to be sex-dependent via disturbances in redox homeostasis, a key event mediating MeHg neurotoxicity. Therefore, we investigated if MeHg-induced changes in key systems of antioxidant defense are sex-dependent. C57BL/6J mice were exposed to MeHg during the gestational and lactational periods, modeling human prenatal and neonatal exposure routes. Dams were exposed to 5 ppm MeHg via drinking water from early gestational period until postnatal day 21 (PND21). On PND21 a pair of siblings (a female and a male) from multiple (5–6) litters were euthanized and tissue samples were taken for analysis. Cytoplasmic and nuclear extracts were isolated from fresh cerebrum and cerebellum and used to determine thioredoxin (Trx) and glutathione (GSH) levels, as well as thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities. The remaining tissue was used for mRNA analysis. MeHg-induced antioxidant response was not uniform for all the analyzed antioxidant molecules, and sexual dimorphism in response to MeHg treatment was evident for TrxR, Trx and GPx. The pattern of response, namely a decrease in males and an increase in females, may impart differential and sex-specific susceptibility to MeHg. GSH levels were unchanged in MeHg treated animals and irrespective of sex. Trx was reduced only in nuclear extracts from male cerebella, exemplifying a structure-specific response. Results from the gene expression analysis suggest posttranscriptional mechanism of sex-specific regulation of the antioxidant response upon MeHg treatment. The study demonstrates for the first time sex-and structure-specific changes in the response of the thioredoxin system to MeHg neurotoxicity and suggests that these differences in antioxidant responses might impart differential susceptibility to developmental MeHg exposure.
Ephedrine induced thioredoxin-1 expression through β-adrenergic receptor/cyclic AMP/protein kinase A/dopamine- and cyclic AMP-regulated phosphoprotein signaling pathway
2013, Cellular Signalling
Citation Excerpt :
Overexpression of Trx-1 prevents progression of heart failure in the Mst1 mice, the development of ventricular remodeling [50] and enhances cardioprotection by postmyocardial neovascularization through the Trx-1–HO-1–VEGF pathway [51]. In the nervous system, Trx-1 acts as a neurotrophic factor for central cholinergic neurons [52]. In the cytoplasm, Trx-1 inhibits nuclear factor kappa B (NF-κB) activation by blocking the dissociation and degradation of IκB [53] and acts as a negative inhibitor of p38 MAPK pathway.
Ephedrine (Eph) is one of alkaloids that has been isolated from the ancient herb ephedra (ma huang) and is used as the treatment of asthma, hypotension and fatigue. However, its molecular mechanism remains unknown. Thioredoxin-1 (Trx-1) is a redox regulating protein, which has various biological activities, including regulating transcription factor DNA binding activity and neuroprotection. In this study, we found that Eph induced Trx-1 expression, which was inhibited by propranolol (β-adrenergic receptor inhibitor), but not by phenoxybenzamine (α-adrenergic receptor inhibitor) in rat pheochromocytoma PC12 cells. Moreover, the increase of Trx-1 expression was inhibited by SQ22536 (adenylyl cyclase inhibitor) and H-89 (protein kinase A inhibitor). Interestingly, the effect of Eph on dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) was similar to Trx-1. Thus, the relationship between Trx-1 and DARPP-32 was further studied. The DARPP-32 siRNA significantly reduced Trx-1 expression, but Trx-1 siRNA did not exchange DARPP-32. These results suggested that Eph induced the Trx-1 expression through β-adrenergic receptor/cyclic AMP/PKA/DARPP-32 signaling pathway. Furthermore, Eph induced PKA-mediated cyclic AMP response element-binding protein (CREB) phosphorylation. Down-regulation of DARPP-32 expression decreased phosphorylated CREB. In addition, Eph had a significant effect on the viability of the rat pheochromocytoma PC12 cells through β-adrenergic receptors. Trx-1 may play an important role in the actions of Eph.
Thioredoxin-1 expression regulated by morphine in SH-SY5Y cells
2012, Neuroscience Letters
Citation Excerpt :
In the nervous system, many studies have shown a positive role for Trx-1. Trx-1 acts as a neurotrophic factor for central cholinergic neurons [13]. We recently reported that Trx-1 plays a critical role in nerve growth factor-mediated neurite outgrowth [3].
Attempts are being made to identify genes targeted by morphine. It is beneficial for developing new treatments that alleviate side-effects of morphine. Thioredoxin-1 is a small ubiquitous protein that has various biological activities, such as the control of redox balance, the inhibition of apoptosis and the modulation of inflammation. In this study, we found that thioredoxin-1 was induced by morphine in SH-SY5Y cells. Furthermore, opioid receptor, PI3K and ERK pathways were involved in morphine-induced increase of thioredoxin-1 expression. These results suggest that thioredoxin-1 maybe play a role in the actions of morphine. More detailed analysis could clarify cellular and molecular mechanisms involved in the actions of morphine.
Protective effect of panaxatriol saponins extracted from Panax notoginseng against MPTP-induced neurotoxicity in vivo
2011, Journal of Ethnopharmacology
Citation Excerpt :
The administration of NGF and BDNF improves functional outcome in animal models of PD (Gash et al., 1996; Chaturvedi et al., 2006). It has been reported that Trx-1 is a neurotrophic factor for central cholinergic neurons (Endoh et al., 1993). Trx-1 plays a critical role in NGF-mediated signal transduction and neurite outgrowth (Bai et al., 2003).
Panaxatriol saponins (PTS), the main constituents extracted from Panax notoginseng, a Chinese herbal medicine, has been shown to be an effective agent on various diseases. Our previous study has demonstrated that PTS is an inducer of thioredoxin-1 (Trx-1) and has a possible potential as a therapeutic agent for Parkinson's disease (PD). However, the effect of PTS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo is unknown.
Using locomotor activity test and traction test, we detected the effect of PTS on MPTP-induced behavioral impairment. Tyrosine hydroxylase, Trx-1, cyclooxygenase-2, pro-caspase-9, pro-caspase-12 and caspase-3 expressions in the anatomical region of substantia nigra pars compacta (SNc) were tested by Western blot.
PTS provided neuroprotection against the loss of dopaminergic neurons and behavioral impairment caused by MPTP. MPTP-induced neuronal death in the SNc was suppressed by PTS through increasing Trx-1 expression, suppressing cyclooxygenase-2 over-expression and inhibiting mitochondria-mediated apoptosis.
PTS, an inducer of Trx-1, has pluripharmacological properties in the protection against PD including enhancing antioxidant activity, acting as neurotrophic factor, modulating inflammation and inhibiting mitochondria-mediated apoptosis.

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Regular ArticleThioredoxin from Activated Macrophages as a Trophic Factor for Central Cholinergic Neurons in Vitro

Abstract

Regular Article
Thioredoxin from Activated Macrophages as a Trophic Factor for Central Cholinergic Neurons in Vitro