GTPases and reactive oxygen species: switches for killing and signaling

Werner, Erica

doi:10.1242/jcs.00937

Cited by 85 publications

(77 citation statements)

References 111 publications

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“…Although Zn (II) itself is reported to be an inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial production of ROS 15 , the generation of ROS at a nontoxic level upon Zn (II) exposure/release has not been described. Nevertheless, O2 •− -producing NAD(P)H oxidases are activated in response to growth factors and oncogenes, and enhanced cell proliferation was observed upon ROS-inducing, low-dose photodynamic treatment [38][39][40][41][42] . Therefore, simultaneous increases in cell proliferation and ROS levels are not conflicting.…”

Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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Zinc is an essential microelement; its importance to skin is shown by severe skin symptoms in hereditary or acquired zinc deficiency, by the improvement of several skin conditions using systemic or topical zinc preparations and by the induced intracellular zinc release upon UVB exposure, which is the main harmful environmental factor to skin. Understanding the molecular background of the role of zinc in skin may help to gain insight into the pathology of skin disorders and to provide evidence for the therapeutic usefulness of zinc supplementation.Herein, we studied the effect of zinc chloride (ZnCl 2 ) exposure on the function of HaCaT keratinocytes, and we found that a non-toxic elevation in the concentration of extracellular zinc (100 µM) facilitated cell proliferation and induced significant alterations in the mRNA expression of NOTCH1, IL8, and cyclooxygenase-2. In addition, we detected increased heme oxygenase-1 (HMOX1) expression and non-toxic generation of superoxide in the first 4 h.Regarding the effect on UVB-induced toxicity, although the level of cyclobutane pyrimidine dimers in keratinocytes pre-treated with zinc for 24 h was reduced 3 h after UVB irradiation, we found significantly enhanced superoxide generation 10 h after UVB exposure in the zinc pre-exposed cells. The overall survival was unaffected; however, there was a decrease in the percentage of early apoptotic cells and an increase in the percentage of late apoptotic plus necrotic cells.Our results suggest that exposure of human keratinocytes to non-toxic concentrations of ZnCl 2 impacts gene expression, cell proliferation and the response to environmental stress in skin. It would be important to further examine the role of zinc in skin and to further clarify if this issue can affect our thinking about the pathogenesis of skin diseases.

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Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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“…In contrast to Fc␥RIII, Fc␥RI is a high-affinity receptor for IgG. Binding of IgG-containing ICs results in production of oxygen radicals, which have been shown to be potent regulators of gene activation through redox signaling (35,36). This may be reflected by chondrocyte death, another parameter of severe cartilage damage, which appeared to be significantly aggravated during IFN␥-stimulated arthritis.…”

Section: Discussionmentioning

confidence: 99%

Joint inflammation and chondrocyte death become independent of Fcγ receptor type III by local overexpression of interferon‐γ during immune complex–mediated arthritis

Nabbe¹,

Boross²,

Holthuysen³

et al. 2005

Arthritis & Rheumatism

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Objective. It has previously been shown that the onset and the degree of joint inflammation during immune complex (IC)-mediated arthritis depend on Fc␥ receptor type III (Fc␥RIII). Local adenoviral overexpression of interferon-␥ (IFN␥) in the knee joint prior to onset of IC-mediated arthritis aggravated severe cartilage destruction. In Fc␥RI Ϫ/Ϫ mice, however, chondrocyte death was not enhanced by IFN␥, whereas matrix metalloproteinase (MMP)-mediated aggrecan breakdown was markedly elevated, suggesting a role for the activating Fc␥RIII in the latter process. We undertook this study to determine the role of Fc␥RIII in joint inflammation and severe cartilage destruction in IFN␥-stimulated IC-mediated arthritis, using Fc␥RIII ؊/؊ mice.Methods. Fc␥RIII ؊/؊ and wild-type (WT) mice were injected in the knee joint with recombinant adenovirus encoding murine IFN␥ (AdIFN␥) or with adenovirus encoding enhanced green fluorescent protein 1 day prior to induction of IC-mediated arthritis. Histologic sections were obtained 3 days after arthritis onset to study inflammation and cartilage damage. MMPmediated expression of the VDIPEN neoepitope was detected by immunolocalization. Chemokine and Fc␥R expression levels were determined in synovial washouts and synovium, respectively.Results. Injection of AdIFN␥ in naive knee joints markedly increased levels of messenger RNA for Fc␥RI, Fc␥RII, and Fc␥RIII. Upon IFN␥ overexpression prior to induction of IC-mediated arthritis, joint inflammation was similar in Fc␥RIII ؊/؊ and WT mice. The percentage of macrophages in the knee joint was increased, which correlated with high concentrations of the macrophage attractant macrophage inflammatory protein 1␣. Furthermore, IFN␥ induced 2-fold and 3-fold increases in chondrocyte death in WT controls and Fc␥RIII ؊/؊ mice, respectively. Notably, VDIPEN expression also remained high in Fc␥RIII ؊/؊ mice.Conclusion. IFN␥ bypasses the dependence on Fc␥RIII in the development of IC-mediated arthritis. Furthermore, both Fc␥RI and Fc␥RIII can mediate MMP-dependent cartilage matrix destruction.

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“…101 In particular, Rac1 and Rac2 are involved in the activation of NOX1, NOX2, and NOX3. [101][102][103] This function of Rac, first demonstrated in neutrophils and other phagocytic cells and later expanded to non-phagocytic cells, 104 is important in both physiological 105 and pathophysiological [106][107][108] settings. Rac1 has been shown to associate with many enzymes necessary for maintaining redox homeostasis in cells.…”

Section: Redox Regulation By Racmentioning

confidence: 99%