Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption

Monroe, Richard K.; Halvorsen, Stanley W.

doi:10.1016/j.neuro.2009.03.007

Cited by 39 publications

(31 citation statements)

References 62 publications

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“…3A). Proteasome dysfunction seems to activate a number of defensive functions directly (H 2 O 2 responsive) and indirectly (cadmium responsive) against oxidative stresses (27).…”

Section: Resultsmentioning

confidence: 99%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Regulations of proliferation and quiescence in response to nutritional cues are important for medicine and basic biology. The fission yeast Schizosaccharomyces pombe serves as a model, owing to the shift of proliferating cells to the metabolically active quiescence (designate G0 phase hereafter) by responding to low nitrogen source. S. pombe G0 phase cells keep alive for months without growth and division. Nitrogen replenishment reinstates vegetative proliferation phase (designate VEG). Some 40 genes required for G0 maintenance were identified, but many more remain to be identified. We here show, using mutants, that the proteasome is required for maintaining G0 quiescence. Functional outcomes of proteasome in G0 and VEG phases appear to be distinct. Upon proteasome dysfunction, a number of antioxidant proteins and compounds responsive to ROS (reactive oxygen species) are produced. In addition, autophagy-mediated destruction of mitochondria occurs, which suppresses the loss of viability by eliminating ROS-generating mitochondria. These defensive responses are found in G0 but not in VEG, suggesting that the main function of proteasome in G0 phase homeostasis is to minimize ROS. Proteasome and autophagy are thus collaborative to support the lifespan of S. pombe G0 phase.cell cycle | cellular quiescence | proteolysis | mitochondria

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“…3A). Proteasome dysfunction seems to activate a number of defensive functions directly (H 2 O 2 responsive) and indirectly (cadmium responsive) against oxidative stresses (27).…”

Section: Resultsmentioning

confidence: 99%

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Takeda

Yoshida

Kikuchi

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Since hepatic protein nitration is remarkably elevated in various chronic diseases including inflammatory diseases, aging, and cancers, it would be valuable to carefully evaluate the role of protein nitration in pathophysiology of these diseases. Alternatively, protein nitration can regulate immune function by interfering with Tyr phosphorylation and concurrent activation of various signal transducer and activators of transcription (STAT) proteins, as reported [159, 160]. …”

Section: Functional Consequences Of Protein Nitration In Acute Andmentioning

confidence: 99%

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Abdelmegeed

Song

2014

Oxidative Medicine and Cellular Longevity

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Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.

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“…Previously, Halvorsen and colleagues have shown JAK/STAT signaling is inhibited by relatively high doses of mercury chloride and cadmium, and that this involves increased oxidative stress (Kaur et al, 2005; Monroe and Halvorsen, 2006a; b; 2009). However, the role of JAK/STAT in MeHg toxicity, especially at very low MeHg levels, as well as potential associated oxidative stress, and their relative contributions to disrupting glial progenitor differentiation remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Low level methylmercury enhances CNTF-evoked STAT3 signaling and glial differentiation in cultured cortical progenitor cells

et al. 2013

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Although many previous investigations have studied how mercury compounds cause cell death, sub-cytotoxic levels may affect mechanisms essential for the proper development of the nervous system. The present study investigates whether low doses of methylmercury (MeHg) and mercury chloride (HgCl2) can modulate the activity of JAK/STAT signaling, a pathway that promotes gliogenesis. We report that sub-cytotoxic doses of MeHg enhance ciliary neurotrophic factor (CNTF) evoked STAT3 phosphorylation in human SH-SY5Y neuroblastoma and mouse cortical neural progenitor cells (NPCs). This effect is specific for MeHg, since HgCl2 fails to enhance JAK/STAT signaling. Exposing NPCs to these low doses of MeHg (30-300 nM) enhances CNTF-induced expression of STAT3-target genes such as glial fibrillary acidic protein (GFAP) and suppressors of cytokine signaling 3 (SOCS3), and increases the proportion of cells expressing GFAP following two days of differentiation. Higher, near-cytotoxic concentrations of MeHg and HgCl2 inhibit STAT3 phosphorylation and lead to increased production of superoxide. Lower concentrations of MeHg effective in enhancing JAK/STAT signaling (30 nM) do not result in a detectable increase in superoxide nor increased expression of the oxidant-responsive genes, heme oxygenase 1, heat shock protein A5 and sirtuin 1. These findings suggest that low concentrations of MeHg inappropriately enhance STAT3 phosphorylation and glial differentiation, and that the mechanism causing this enhancement is distinct from the reactive oxygen species -associated cell death observed at higher concentrations of MeHg and HgCl2.

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Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption

Cited by 39 publications

References 62 publications

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Synergistic roles of the proteasome and autophagy for mitochondrial maintenance and chronological lifespan in fission yeast

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Low level methylmercury enhances CNTF-evoked STAT3 signaling and glial differentiation in cultured cortical progenitor cells

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