Expression and regulation of peroxiredoxin 5 in human osteoarthritis

Wang, Min Xia; Wei, Ai-Qun; Yuan, Jun; Trickett, Annette; Knoops, Bernard; Murrell, George A. C.

doi:10.1016/s0014-5793(02)03511-1

Cited by 57 publications

(48 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Examples of antioxidant enzymes are the superoxide dismutases (SOD), glutathione peroxidase, catalase, and a novel family of peroxidases, the peroxiredoxins (PRX). Increased SOD activity and increased expression of PRX5 has been reported in OA [17]. The present study show that MnSOD and PRX2 are more abundant in SFs of RA or OA, which suggests that they may play a protective role against oxidative stress in inflammatory arthritis.…”

Section: Discussionsupporting

confidence: 69%

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

Zhou

Wang

et al. 2008

Clin Rheumatol

View full text Add to dashboard Cite

There is mounting evidence indicating that the synovial fibroblasts (SFs) contribute to the pathogenesis of rheumatoid arthritis (RA). The present study showed the differential proteins expression pattern of SFs from patients with RA or osteoarthritis (OA) and healthy control. Cellular proteins of cultured SFs were subjected to 2-DE and visualized by silver nitrate staining. A total of 49 spots that were statistically and differentially overexpressed in RA or OA in comparison to healthy ones were identified by MALDI-TOF-MS, and 25 proteins were successfully identified. Western blot was used to further verify some of the differential proteins. These proteins included enzymatic and structural proteins, signal transduction proteins, calcium binding protein, etc. From all of the identified proteins, a number of proteins have been implicated that involved in the healthy or pathological SFs function (e.g., S100A4, S100A10, cathepsin D) or that have potential diagnostic and prognostic value for RA (α-enolase and TPI) or that may be the new therapeutic targets (Annexin, SOD, PRX).

show abstract

Section: Discussionsupporting

confidence: 69%

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

Zhou

Wang

et al. 2008

Clin Rheumatol

View full text Add to dashboard Cite

show abstract

“…Intracellular reactive oxygen species generation was measured with the cell-permeable dye, 2Ј,7Ј-dichloro-fluorescein-diacetate (Sigma; refs. 28,29). This compound readily diffuses into cells and becomes highly fluorescent when oxidized by superoxide, H 2 O 2 , or hydroxyl radicals (28,29).…”

Section: Methodsmentioning

confidence: 99%

Potent Antitumor Activity of Novel Iron Chelators Derived from Di-2-Pyridylketone Isonicotinoyl Hydrazone Involves Fenton-Derived Free Radical Generation

Chaston

Watts

Yuan

et al. 2004

Clinical Cancer Research

Self Cite

121

100

View full text Add to dashboard Cite

Purpose: The development of novel and potent iron chelators as clinically useful antitumor agents is an area of active interest. Antiproliferative activity of chelators often relates to iron deprivation or stimulation of iron-dependent free radical damage. Recently, we showed that novel iron chelators of the di-2-pyridylketone isonicotinoyl hydrazone (PKIH) class have potent and selective antineoplastic activity (E. Becker, et al., Br. J. Pharmacol., 138: 819 -30, 2003). In this study, we assessed the effects of the PKIH analogues on the redox activity of iron in terms of understanding their antitumor activity.Experimental Design: We tested the PKIH analogues for their ability to promote iron-mediated ascorbate oxidation, benzoate hydroxylation, and plasmid degradation. Subsequent experiments assessed their ability to bind DNA, inhibit topoisomerase I, and cause DNA damage. To measure intracellular reactive oxygen species, we used the redoxsensitive probe, 2,7-dichloro-fluorescein-diacetate, to measure intracellular PKIH-dependent redox activity.Results: The PKIH analogues had relatively little effect on ascorbate oxidation in the presence of Fe(III) but stimulated benzoate hydroxylation and plasmid DNA degradation in the presence of Fe(II) and H 2 O 2 . These ligands could not inhibit DNA topoisomerase I or cause DNA damage in intact cells. PKIH markedly increased the intracellular generation of reactive oxygen species, and this was inhibited by catalase. This enzyme also decreased the antiproliferative effect of PKIH, indicating H 2 O 2 played a role in its cytotoxic activity.Conclusions: Our results suggest that the antiproliferative effects of these chelators relates to intracellular iron chelation, followed by the stimulation of iron-mediated free radical generation via the so-formed iron complex.

show abstract

“…71 71 for 10 minutes at 37°C. Cells were then incubated with H 2 DCF-DA (5 M) for 20 minutes at 37°C and washed twice.…”

Section: Intracellular Reactive Oxygen Species Assaymentioning

confidence: 99%

“…Cells were then incubated with H 2 DCF-DA (5 M) for 20 minutes at 37°C and washed twice. 71 The fluorescence of oxidized DCF in cells was measured using flow cytometry. 71 …”

Section: Intracellular Reactive Oxygen Species Assaymentioning

confidence: 99%

“…To test this, intracellular ROS were measured by flow cytometry using the H 2 DCF-DA probe, which becomes fluorescent when oxidized by O 2 Ϫ , H 2 O 2 , or HOϪ. 71 Incubating M109 cells with Dp44mT (1 M) increased the levels of oxidized probe as a function of time. After 2 hours, a 25% Ϯ 10% increase in oxidized H 2 DCF-DA fluorescence was found compared with the 0-hour time point, and this increased to 486% Ϯ 96% after 48 hours.…”

Section: Intracellular Ros Generation After Incubation With Dp44mtmentioning

confidence: 99%

See 1 more Smart Citation

Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment

Yuan

Lovejoy

Richardson

2004

Blood

Self Cite

357

754

View full text Add to dashboard Cite

Aroylhydrazone and thiosemicarbazone iron (Fe) chelators have potent antitumor activity. The aim of the current study was to examine the antitumor effects and mechanisms of action of a novel series of Fe chelators, the di-2-pyridyl thiosemicarbazones. Of 7 new chelators synthesized, 4 showed pronounced antiproliferative effects. The most active chelator was Dp44mT, which had marked and selective antitumor activity-for example, an IC 50 of 0.03 M in neuroepithelioma cells compared with more than 25 M in mortal fibroblasts. Indeed, this antiproliferative activity was the greatest yet observed for an Fe chelator. Efficacy was greater than it was for the cytotoxic ligand 311 and comparable to that of the antitumor agent doxorubicin. Strikingly, Dp44mT significantly (P < .01) decreased tumor weight in mice to 47% of the weight in the control after only 5 days, whereas there was no marked change in animal weight or hematologic indices. IntroductionIron (Fe) is essential for proliferation, and many studies have shown that tumor cells are more sensitive to Fe deprivation than normal cells. [1][2][3][4][5][6][7][8][9][10][11] This sensitivity probably exists because cancer cells have greater Fe requirements than their normal counterparts [12][13][14][15] and because cancer cells express higher levels of the Fe-containing enzyme, ribonucleotide reductase (RR), which is the critical rate-limiting step in DNA synthesis. [16][17][18][19][20][21] Many in vitro 2,4,[7][8][9][21][22][23][24][25][26][27][28] and in vivo 6,29,30 studies and clinical trials 3,5,[31][32][33][34][35][36] have demonstrated that chelators are effective antiproliferative agents (for reviews, see Hershko,10 Lovejoy and Richardson, 11 and Richardson 37 ). The most well-studied chelator is desferrioxamine (DFO; Figure 1). 10,11 However, its short half-life and low efficacy at permeating membranes limit its antiproliferative activity. 22,38 Indeed, these factors probably resulted in its failure to inhibit tumor growth in some studies. 39,40 One group of ligands with high Fe chelation efficacy is the pyridoxal isonicotinoyl hydrazone (PIH) class. [41][42][43][44] We characterized PIH analogs that show far greater Fe chelation efficacy and antiproliferative activity than DFO. 23,24,45 Some of these ligands, such as 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311; Figure 1) inhibit RR activity 9 and affect the expression of molecules vital for cell cycle control. [46][47][48] One mechanism by which chelators and other factors (eg, oxidative stress) cause tumor cell death may be through the induction of apoptosis. 22,24,[49][50][51][52][53][54][55][56] However, the precise mechanisms involved in chelator-mediated apoptosis remain unclear, particularly for aroylhydrazone ligands.The caspase enzymes are common executors of apoptosis. 52,57,58 Two caspase-activating cascades that regulate apoptosis have been described; one is initiated through death receptors (eg, CD95), and the other is triggered by changes in mitochondrial integrity. 52,59,60 In the ...

show abstract

Expression and regulation of peroxiredoxin 5 in human osteoarthritis

Cited by 57 publications

References 35 publications

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

Analyses of differential proteome of human synovial fibroblasts obtained from arthritis

Potent Antitumor Activity of Novel Iron Chelators Derived from Di-2-Pyridylketone Isonicotinoyl Hydrazone Involves Fenton-Derived Free Radical Generation

Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment

Contact Info

Product

Resources

About