Oxidation of Proteinaceous Cysteine Residues by Dopamine-Derived H2O2 in PC12 Cells

Kim, Jae Ryong; Yoon, Hae Won; Lee, Seung Rock; Rhee, Sue Goo

doi:10.1006/abbi.2001.2691

Cited by 29 publications

(18 citation statements)

References 56 publications

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“…The antilymphoma outcomes are, however, independent of both DAT and DA receptors, being delivered instead by extracellular oxidation. DA-induced toxicity through the generation of reactive oxidation species is well documented among cell line models of PD (26)(27)(28). In general, the concentrations of DA required for affecting neuronal cells via this route appear substantially higher than against the lymphoma lines used here.…”

Section: Discussionmentioning

confidence: 80%

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Meredith

Holder

Rosén

et al. 2006

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

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Human B lymphocytes and derived lines from a spectrum of B cell malignancy were studied for expression of dopaminergic pathway components and for their cytostatic response to the catecholamine and related, potentially therapeutic compounds. Proliferating normal lymphocytes and dividing malignant clones rapidly arrested on exposure to dopamine in the low (<10 M) micromolar range. The antiparkinsonian drugs L-DOPA and apomorphine (particularly) were similarly antiproliferative. With the exception of D4, dopamine receptors D1-D5 were variably expressed among normal and neoplastic B cell populations, as was the dopamine transporter. Transcripts for D1 and D2 were frequently found, whereas D3 and D5 revealed restricted expression; dopamine transporter was detected in most cases. Nevertheless, pharmacological analysis disclosed that dopamine targeted cycling B cells independent of these structures. Rather, oxidative stress constituted the primary mechanism: the catecholamine's actions being mimicked by hydrogen peroxide and reversed by exogenous catalase, and evidence for the intracellular redox protein thioredoxin contributing protection. Among proliferating clones, growth arrest was accompanied by cell death in populations deplete in antiapoptotic Bcl-2: resting lymphocytes escaping low micromolar dopamine toxicity. Dysregulated bcl-2 expression, although preventing oxidative-induced caspase-dependent apoptosis, by itself conferred only minor protection against dopamine cytostasis. The selective impact of dopamine on lymphocytes that are in active cycle indicates an axis for therapeutic intervention not only in B cell neoplasia but also in lymphoproliferative disturbances generally. Rational tailoring of drug delivery systems already in development for Parkinson's disease could provide ideal vehicles for carrying the oxidative hit directly to the target populations.apoptosis ͉ oxidative stress ͉ Parkinson's disease ͉ Bcl-2 ͉ monoamines

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Section: Discussionmentioning

confidence: 80%

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Meredith

Holder

Rosén

et al. 2006

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

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“…These included PLCγ1 and Akt2, both well-known mediators of PDGF signaling. Redox sensitivity of PLCγ1 was reported in PC12 cells stimulated with dopamine (11). Western blot analysis of streptavidin-agarose pull-down samples from PDGF-stimulated cells lysed in the presence of DCP-Bio1 showed increased PLCγ1 oxidation with PDGF stimulation compared with unstimulated control (Fig.…”

mentioning

confidence: 75%

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

Wani

Qian

Yin

et al. 2011

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

130

115

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Isoform-specific signaling of Akt, a major signaling hub and a prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, and posttranslational modifications are believed to underlie isoform-specific signaling of Akt. The studies reported here show inhibition of Akt2 activity under physiologically relevant conditions of oxidation created by PDGF-induced reactive oxygen species. Combined MS and functional assays identified Cys124 located in the linker region between the N-terminal pleckstrin homology domain and the catalytic kinase domain as one of the unique regulatory redox sites in Akt2 with functional consequence on PDGF-stimulated glucose uptake. A model is proposed describing the consequence of increased endogenous oxidation induced by extracellular cues such as PDGF on Akt2 activity.disulfide | receptor tyrosine kinase | DCF | DCP-Bio1 P KB/Akt is a major signaling hub between cytokine, growth factor, and integrin signaling pathways of consequence to many biological processes. Energy storage, protein synthesis, cell survival and growth, cell cycle progression, and cell death are differentially regulated by the three known isoforms of Akt kinase: Akt1/PKBα, Akt2/PKBβ, and Akt3/PKBγ (1). Although the molecular features underlying isoform-specific functional predominance are largely unknown, hypotheses to explain Akt isoform specificity include selective interactions with substrates and/ or binding partners, tissue specificity, subcellular location, and temporal changes in activation profiles of Akt isoforms (2). Posttranslational modifications may contribute to this isoform-specific signaling, but reports of modifications are lacking.Reactive oxygen species (ROS) are integral to cytokine and growth factor signaling; ROS generation in response to these extracellular cues is well documented (3). Earlier reports, in particular from Sundaresan et al. (4), showed ROS generation in response to PDGF stimulation of vascular smooth muscle cells and suggested that H 2 O 2 can relay redox signals to regulate physiological signaling in response to growth factors. More recently, it has been shown that PrxI phosphorylation at Y194 by Src family tyrosine kinases inhibited PrxI and resulted in H 2 O 2 accumulation at the cellular membrane where receptor tyrosine kinase activation occurs (5). Unanswered questions include which proteins are oxidized by receptor tyrosine kinase-induced ROS, which specific cysteine site(s) undergo oxidation, and the consequence of oxidation on activity of these proteins and propagation of receptor tyrosine kinase signaling. Recently, the synthesis of several dimedone-based chemoselective reagents capable of specific labeling of sulfenic acid oxidized proteins was reported; these reagents allow for specific enrichment and identification of oxidized proteins (6-10). In this study, we used a biotin-tagged 1,3-cyclohexadione derivative, DCP-Bio1 (Fig. 1A), to investigate isoform-specific effects of PDGF-induced ...

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“…46 Recently, it has been reported that the exquisite sensitivity of GADPH to peroxide is conferred by a specific selenocysteine located at the catalytic site of the enzyme. 47 Another example of a low-affinity peroxide effect is its inhibition of skeletal muscle Ca 2 þ -activated K þ channel, which in artificial bilayers showed a K i 410 mM. 48 A wellknown effect of peroxide in combination with transition metals is the production of highly reactive hydroxyl radicals in the Fenton or Haber-Weiss reactions; however, such mechanisms do not seem to be relevant as chelation of transition metals with desferroxamine failed to inhibit the calcium rise.…”

Section: Discussionmentioning

confidence: 99%

A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

et al. 2004

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Oxidative stress releases intracellular calcium, which plays a pathogenic role in mammalian cell death. Here we report a search for the source of oxidative calcium in HeLa cells based on confocal epifluorescence microscopy. H 2 O 2 caused a rapid increase in cytosolic calcium, which was followed by mitochondrial Ca 2 þ loading. Combined mitochondrial uncoupling with full depletion of thapsigargin-sensitive stores abrogated inositol 1,4,5-trisphosphate-mediated calcium release but failed to inhibit H 2 O 2 -induced calcium release, observation that was confirmed in MDCK cells. Prevention of peroxide-induced acidification with a pH clamp was also ineffective, discarding a role for endosomal/lysosomal Ca 2 þ / H þ exchange. Lysosomal integrity was not affected by H 2 O 2 . Mature human erythrocytes also reacted to peroxide by releasing intracellular calcium, thus directly demonstrating the cytosolic source. Glutathione depletion markedly sensitized cells to H 2 O 2 , an effect opposite to that achieved by DTT. Iron chelation was ineffective. In summary, our results show the existence of a previously unrecognized sulfhydrylsensitive source of pathogenic calcium in the cytosol of mammalian cells.

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Oxidation of Proteinaceous Cysteine Residues by Dopamine-Derived H2O2 in PC12 Cells

Cited by 29 publications

References 56 publications

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Isoform-specific regulation of Akt by PDGF-induced reactive oxygen species

A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death

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