ArticleThe Journal of biological chemistry2008
A direct redox regulation of protein kinase C isoenzymes mediates oxidant-induced neuritogenesis in PC12 cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Metal-Chelating Self-Assembling Peptide Nanofiber Scaffolds for Modulation of Neuronal Cell Behavior.Micromachines · 2023Article
- Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response.Nature communications · 2021Article
- The mitochondrial PKCδ/retinol signal complex exerts real-time control on energy homeostasis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Subplasmalemmal hydrogen peroxide triggers calcium influx in gonadotropes.The Journal of biological chemistry · 2018Article
- Live-cell imaging approaches for the investigation of xenobiotic-induced oxidant stress.Biochimica et biophysica acta · 2016Review
- Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid.Redox biology · 2016Article
- Toxic and transcriptional responses of PC12 cells to soluble tungsten alloy surrogates.Toxicology reports · 2015Article
- Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase.American journal of physiology. Cell physiology · 2014Article
- Redox signaling in cardiovascular health and disease.Free radical biology & medicine · 2013Review
- Peroxiredoxin II regulates effector and secondary memory CD8+ T cell responses.Journal of virology · 2012Article
- Zinc and the modulation of redox homeostasis.Free radical biology & medicine · 2012Review
- Green tea polyphenols precondition against cell death induced by oxygen-glucose deprivation via stimulation of laminin receptor, generation of reactive oxygen species, and activation of protein kinase Cε.The Journal of biological chemistry · 2012Article
- Reactive oxygen species regulate nucleostemin oligomerization and protein degradation.The Journal of biological chemistry · 2011Article
- Article
- Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.Antioxidants & redox signaling · 2010Review
- Cellular stress responses, mitostress and carnitine insufficiencies as critical determinants in aging and neurodegenerative disorders: role of hormesis and vitagenes.Neurochemical research · 2010Article
- Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species.Journal of neuroscience research · 2010Article
- Regulation of intermediary metabolism by the PKCdelta signalosome in mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Transient glutathione depletion determines terminal differentiation in HL-60 cells.Oxidative medicine and cellular longevityArticle
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
In this study, we have used the PC12 cell model to elucidate the mechanisms by which sublethal doses of oxidants induce neuritogenesis. The xanthine/xanthine oxidase (X/XO) system was used for the steady state generation of superoxide, and CoCl(2) was used as a representative transition metal redox catalyst. Upon treatment of purified protein kinase C (PKC) with these oxidants, there was an increase in its cofactor-independent activation. Redox-active cobalt competed with the redoxinert zinc present in the zinc-thiolates of the PKC regulatory domain and induced the oxidation of these cysteine-rich regions. Both CoCl(2) and X/XO induced neurite outgrowth in PC12 cells, as determined by an overexpression of neuronal marker genes. Furthermore, these oxidants induced a translocation of PKC from cytosol to membrane and subsequent conversion of PKC to a cofactor-independent form. Isoenzyme-specific PKC inhibitors demonstrated that PKCepsilon plays a crucial role in neuritogenesis. Moreover, oxidant-induced neurite outgrowth was increased with a conditional overexpression of PKCepsilon and decreased with its knock-out by small interfering RNA. Parallel with PKC activation, an increase in phosphorylation of the growth-associated neuronal protein GAP-43 at Ser(41) was observed. Additionally, there was a sustained activation of extracellular signal-regulated kinases 1 and 2, which was correlated with activating phosphorylation (Ser(133)) of cAMP-responsive element-binding protein. All of these signaling events that are causally linked to neuritogenesis were blocked by antioxidant N-acetylcysteine (both L and D-forms) and by a variety of PKC-specific inhibitors. Taken together, these results strongly suggest that sublethal doses of oxidants induce neuritogenesis via a direct redox activation of PKCepsilon.
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