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M S Seo

Publications and source records attributed to M S Seo.

At least 19 recordsLinked to original sources
PubMed2001

Preparation, structure, and properties of the corner-shared double cubes [Mo(6)HgQ(8)(H(2)O)(18)](8+) (Q = S, Se) and tungsten analogues.

The purple corner-shared double cube [Mo(6)HgS(8)(H(2)O)(18)](8+) derivative of green [Mo(3)S(4)(H(2)O)(9)](4+), obtained under air-free conditions by the reaction with Hg(0) (metal), is also formed with Hg(I)(2). The Hg(I)(2) reaction is accounted for by the disproportionation Hg(I)(2) <==> Hg(0) + Hg(II), which is a source of Hg(0). X-ray crystallographic information on the blue partially Cl(-) substituted cucurbituril supramolecular assemblies [Mo(6)HgQ(8)Cl(4)(H(2)O)(14)](C(36)H(36)N(24)O(12))Cl(4).14H(2)O (1) and of the Se analogue [Mo(6)HgSe(8)Cl(4) (H(2)O)(14)](C(36)H(36)N(24)O(12))Cl(4).14H(2)O (2) have been determined. The product [W(6)HgSe(8)Cl(4)(H(2)O)(14)](C(36)H(36)N(24) O(12)) Cl(4).14H(2)O (3) has also been obtained, but there is no evidence for [W(6)HgS(8)(H(2)O)(18)](8+) and related forms. The formation of [Mo(6)HgS(8)(H(2)O)(18)](8+) by the reaction of [Mo(3)S(4) (H(2)O)(9)](4+) with Hg(0) under anaerobic conditions maximizes after approximately 40 h in 2.0 M HCl, but requires longer reaction time ( approximately 120 h) in 2.0 M Hpts (p-toluenesulfonic acid) and in 2 M HClO(4) ( approximately 6 days). In 2.0 M HCl there is little absorbance increase until [Mo(3)S(4)(H(2)O)(9)](4+) exceeds 1.2 x 10(-)(3) M, which is explained by a dependence of the formation K (265 M(-1)) on [Mo(3)S(4)(H(2)O)(9)(4+)](2). Furthermore, on dilution of column-purified [Mo(6)HgS(8)(H(2)O)(18)](8+), Beer's law is not obeyed and equilibria involving 2[Mo(3)S(4)(H(2)O)(9)](4+) are apparent. The kinetics of formation of [Mo(6)HgS(8)(H(2)O)(18)](8+) is first-order in [Mo(3)S(4)(H(2)O)(9)](4+), consistent with rate-determining formation of the single cube [Mo(3)HgS(4)(H(2)O)(x)](4+). The oxidations of [Mo(6)HgS(8)(H(2)O)(18)](8+) with [Fe(H(2)O)(6)](3+) and [Co(dipic)(2)](-) are complicated by the release of [Hg(H(2)O)(6)](2+), which also functions as an oxidant. Similar results are obtained for [Mo(6)HgSe(8)(H(2)O)(18)](8+) and the less extensively studied [W(6)HgSe(8)(H(2)O)(18)](8+).

Journal Article↗
PubMed2001

Preparation, structure, and reactivity of Ge-containing heterometallic cube derivatives of [M(3)E(4)(H2O)(9)](4+) (M = Mo, W; E = S, Se).

Studies leading to the incorporation of Group 14 germanium into the incomplete cuboidal clusters [M(3)E(4)(H2O)(9)](4+) (M = Mo, W; E = S, Se) have been carried out. From the clusters [Mo(3)E(4)(H2O)(9)](4+), corner-shared double cubes [Mo(6)GeE(8)(H2O)(18)] are obtained with GeO, by heating with Ge powder at 90 degrees C, or by heating with GeO(2) in the presence of H(3)PO(2) as reductant at 90 degrees C, illustrating the dominance of the double cubes. The yellow-green single cube [Mo(3)GeS(4) (H2O)(12)](6+) is only obtained by controlled air oxidation of [Mo(6)GeS(8)(H2O)(18)](8+) over a period of approximately 4 days followed by Dowex purification. In the case of the trinuclear clusters [W(3)E(4)(H2O)(9)](4+), the single cubes [W(3)GeE(4)(H2O)(12)](6+) are dominant and prepared by the reactions with GeO, or GeO(2)/H(3)PO(2). Conversion of [W(3)GeE(4)(H2O)(12)](6+) to the corresponding double cubes is achieved by reductive addition with BH(4)(-) in the presence of a further equivalent of [W(3)E(4)(H2O)(9)](4+). The crystal structures (pts(-) = p-toluene-sulfonate) of [Mo(6)GeS(8)(H2O)(18)](pts)(8).28H2O, (1); [W(6)GeS(8)(H2O)(18)](pts)(8).23H2O, (2); and [Mo(6)GeSe(8)(H2O)(18)](pts)(8).8H2O, (3); have been determined, of which (2) is the first structure of a W(6) double cube. The M-M bond lengths of approximately 2.7 A are consistent with metal-metal bonding, and the M-Ge of approximately 3.5 A corresponds to nonbonding separations. Of the Group 13-15 corner-shared double cubes from [Mo(3)S(4)(H2O)(9)](4+), [Mo(6)GeS(8)(H2O)(18)](8+) is the least reactive with [Co(dipic)(2)](-) as oxidant (0.077 M(-1) s(-1)), and [Mo(6)SnS(8)(H2O)(18)](8+) is next (14.9 M(-1) s(-1)). Both Ge and Sn (Group 14) have an even number of electrons, resulting in greater stability. In contrast, [W(6)GeS(8)(H2O)(18)](8+) is much more reactive (7.3 x 10(3) M(-1) s(-1)), and also reacts more rapidly with O(2).

Journal Article↗
PubMed2001

Mechanism of refractory ceramic fiber- and rock wool-induced cytotoxicity in alveolar macrophages.

OBJECTIVES: Man-made vitreous fibers (MMVFs) can induce cytotoxicity in a way similar to that of other particles, including silica and asbestos fibers. However, as yet the mechanism of MMVF-induced cytotoxicity is still not clear. This report aims to clarify the mechanism of MMVF-induced cytotoxicity in the alveolar macrophage (AM). In this mechanism, an attempt to prove the involvement of the adenosine triphosphate (ATP) generation system and the polyinosinic acid-inhibitable scavenger receptors was made. METHODS: Several parameters were observed for cytotoxicity, such as cell viability, the release of lactic dehydrogenase (LDH) and ATP levels in rat AM's that were treated with refractory ceramic fibers (RF2) and rock wool (RW1). A specially designed ATP generation system was used to determine the effect of MMVF on ATP generation. A scavenger receptor ligand was applied to evaluate the relationship between scavenger receptors and MMVF-induced ATP depletion. RESULTS: A 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that both RF2 and RW1 caused a decrease in cell viability and this decrease was concentration-dependent. RF2 and RW1 increased the release of LDH with increasing fiber concentration. From these parameters, RF2 was shown to exhibit greater cytotoxicity than did RW1. Both fibers decreased the intracellular ATP content and this decrease was concentration-dependent. The decrease was more pronounced in RW1 than in RF2 at all fiber concentrations. These fibers suppressed succinate-triggered oxygen consumption. Polyinosinic acid, a ligand of the scavenger receptor, inhibited the MMVF-induced decrease in ATP concentration. CONCLUSION: These results suggest that RF2 and RW1 can induce cytotoxicity and ATP depletion in the AM through the polyinosinic acid-inhibitable scavenger receptor. ATP depletion was the important factor in MMVF cytotoxicity, especially by RW1.

Adenosine Triphosphate↗
PubMed2001

Triangular transchamber suture.

A 64-year-old woman with a fibrous membrane at the lens plane after traumatic loss of all the iris and massive intraocular hemorrhage had posterior chamber intraocular lens (PCIOL) implantation anterior to the fibrous membrane with a triangular transchamber suture to prevent possible PCIOL-corneal touch and enhance the stability of the PCIOL. After 3 years, the PCIOL remained in a good position and visual rehabilitation was satisfactory and without complications.

Eye Injuries↗
PubMed2001

Distraction osteogenesis after membranous bone onlay grafting in a dog model.

PURPOSE: The purpose of this experiment was to study the possibility of distraction osteogenesis in a membranous bone onlay graft to the mandible and to clarify the histology of the bone repair. MATERIALS AND METHODS: Four dogs, 5 months of age at the beginning of the experiment, were used for this study. The zygomatic arch was exposed in the subperiosteal plane, and a 3-cm long, full-thickness portion of the arch was harvested. The lateral surface of the mandibular body was exposed in the subperiosteal plane, and the bone was fixed to the lateral surface as a membranous onlay graft using screws. A vertical osteotomy through the graft and underlying mandibular body was done postoperatively at week 1 in dog 1, week 2 in dog 2, week 3 in dog 3, and week 4 in dog 4. An external distraction device was applied to the mandibular body, and distraction was started 7 days after the operation at a rate of 1 mm/d for 10 days. After completion of distraction, the device was left in place for 6 weeks to allow for bony consolidation. Radiographs were carried out at 2, 4, and 6 weeks postdistraction. All dogs were killed 6 weeks after distraction. RESULTS: New bone between the native underlying mandibular segments was generated in the distraction zone in all dogs. New bone was not generated between the segments of the membranous bone onlay graft in dog 1, but was generated in dog 2, dog 3, and dog 4. However, in dogs 2 and 3, the new bone between the segments was less firm, with more fibrous tissue, than the bone between the native underlying mandibular segments. Histologically, the distraction gap between the segments of the membranous bone onlay graft in dogs 2 and 3 was composed of considerable fibrous tissue in the central zone and activated osteoblastic cells forming new bone in the margins. In dog 4, there was much more osteoblastic activity in the distraction gap, and the new bone had the appearance of almost normal cortical bone. CONCLUSION: These findings show that distraction osteogenesis is possible in a membranous bone onlay graft and suggest that the distraction should be performed at least 4 weeks after the onlay grafting.

Animals↗
PubMed2000

Cellular distribution of isozymes of protein kinase C in septal olfactory epithelium of mice.

To determine the presence of protein kinase C (PKC) isozymes in the septal olfactory epithelium of mice (mSOE), western blotting and immunohistochemistry were performed using antibodies against PKC isozymes. With the exception of PKC-betaI, all of the PKC isozymes were detected in the whole lysate of septal tissue layer and apparent molecular weights for each isoform were found. PKC-alpha, PKC-gamma and PKC-epsilon were detected in the olfactory glandular cells of the lamina propria, and PKC-betaI and PKC-betaII were located in the microvillar cells. Neither novel PKC nor atypical PKC was detected in olfactory glandular cells or microvillar cells, except for PKC-epsilon. PKC-lambda was localized in the mucous layer of the mSOE. Meanwhile, PKC-delta and PKC-xi were distributed in the receptor cells in the mSOE. These data demonstrate the isoform-specific expression of PKC in mSOE and suggest a role for the novel and atypical types of PKC in olfactory transduction.

Animals↗
PubMed2000

Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate.

Peroxidases of the peroxiredoxin (Prx) family contain a Cys residue that is preceded by a conserved sequence in the NH(2)-terminal region. A new type of mammalian Prx, designated PrxV, has now been identified as the result of a data base search with this conserved Cys-containing sequence. The 162-amino acid PrxV shares only approximately 10% sequence identity with previously identified mammalian Prx enzymes and contains Cys residues at positions 73 and 152 in addition to that (Cys(48)) corresponding to the conserved Cys. Analysis of mutant human PrxV proteins in which each of these three Cys residues was individually replaced with serine suggested that the sulfhydryl group of Cys(48) is the site of oxidation by peroxides and that oxidized Cys(48) reacts with the sulfhydryl group of Cys(152) to form an intramolecular disulfide linkage. The oxidized intermediate of PrxV is thus distinct from those of other Prx enzymes, which form either an intermolecular disulfide or a sulfenic acid intermediate. The disulfide formed by PrxV is reduced by thioredoxin but not by glutaredoxin or glutathione. Thus, PrxV mutants lacking Cys(48) or Cys(152) showed no detectable thioredoxin-dependent peroxidase activity, whereas mutation of Cys(73) had no effect on activity. Immunoblot analysis revealed that PrxV is widely expressed in rat tissues and cultured mammalian cells and is localized intracellularly to cytosol, mitochondria, and peroxisomes. The peroxidase function of PrxV in vivo was demonstrated by the observations that transient expression of the wild-type protein, but not that of the Cys(48) mutant, in NIH 3T3 cells inhibited H(2)O(2) accumulation and activation of c-Jun NH(2)-terminal kinase induced by tumor necrosis factor-alpha.

Amino Acid Sequence↗
PubMed2000

Adenosine triphosphate-induced heterologous desensitization of endothelin-1- and glutamate-evoked calcium increases in cultured rat cortical astrocytes.

In rat cortical astrocytes, we investigated the occurrence of cross-talks between purinoceptor and endothelin (ET) receptor, or glutamate receptor. The treatments of adenosine triphosphate (ATP), ET-1, and glutamate induced the increase of intracellular calcium level in the astrocytes. In repetitive additions of ATP to astrocytes, the second application of ATP exhibited comparable amplitude of calcium response, but the stimulation with ATP completely blocked subsequent ET-1- or glutamate-evoked calcium responses showing complete heterologous desensitization. In contrast, ET-1 and glutamate failed to desensitize the response elicited by ATP. Preincubation with sphingosine, a protein kinase C (PKC) inhibitor, reversed the ATP-induced desensitization of ET-1- and glutamate-evoked calcium responses. Taken together, these results demonstrate the resistance of purinoceptor to homologous desensitization, and unidirectional desensitization between ATP and other receptors such as ET and glutamate receptors, suggesting a dominant role of purinoceptor in modulating calcium signal of astrocytes.

Adenosine Triphosphate↗
PubMed2000

Activation of telomerase by silica in rat lung.

By measuring the activity of telomerase in a silica-instilled rat lung, the study found a significant increase in telomerase activity compared to that of the control. Pneumoconiosis displays the characteristics of fibroblast-proliferation and accumulation of collagen, which finally causes the pathologic changes of irreversible and progressive fibrosis of the lung. On the basis of the hypothesis that cellular proliferation may trigger telomerase-activity, the experiment was carried out with telomerase-activation in silicosis. Silica-instilled rat lungs showed increased activity of telomerase, which was measured by TRAP (telomeric repeat amplification protocol) assay, at the time of the 1st, 5th and 8th week after intratracheal instillation of silica in vivo. However, no activity was shown in silica-co-cultured fibroblast in vitro. By summarizing these results, the activity of telomerase is thought to be a very sensitive marker for the evaluation of pathogenicity, showing cellular immortalization in an experimental silicosis model.

Animals↗
PubMed2000

Photoreceptor-specific expression of platelet-derived growth factor-B results in traction retinal detachment.

Expression of platelet-derived growth factor (PDGF)-A and PDGF-B is increased in patients with proliferative retinopathies in which traction retinal detachments occur. Previous studies have demonstrated that increased expression of PDGF-A in the retina of transgenic mice results in retinal gliosis due to proliferation of astrocytes with different retinal phenotypes based on the time of onset and location of the PDGF-A production. In this study, we investigated the effects of PDGF-B in the retina using gain-of-function transgenic mice that express PDGF-B in photoreceptors. These mice show proliferation of astrocytes, pericytes, and, to a lesser extent, endothelial cells, resulting in ectopic cells on the surface and extending into the retina. The sheets of cells exert traction on the retina resulting in traction retinal detachments similar to those seen in humans with proliferative retinopathies. These studies suggest that PDGF-B has more dramatic effects in the retina than PDGF-A, because it acts on additional cell types, in particular on pericytes, which have a highly developed contractile apparatus. These studies in the retina suggest a means that could be used in other tissues throughout the body to achieve graded PDGF effects. They also provide a new model of traction retinal detachment that can be used to investigate new treatments for patients with proliferative retinopathies.

Animals↗
PubMed2000

Platelet-derived growth factor-A-induced retinal gliosis protects against ischemic retinopathy.

Retinal astrocytes are located in the nerve fiber layer and along retinal blood vessels and have been hypothesized to participate in the induction and maintenance of the blood-retinal barrier. Platelet-derived growth factor-A (PDGF-A) is normally produced by retinal ganglion cells and is involved in astrocyte recruitment and proliferation. We used gain-of-function transgenic mice that express PDGF-A in photoreceptors to explore the roles of PDGF-A and astrocytes in the retina. Transgene-positive mice developed glial infiltration of the inner retina and had significantly less oxygen-induced retinal vascular closure and no neovascularization compared with littermate controls, which had prominent vascular closure and neovascularization. The increased survival of endothelial cells in transgenic mice in the face of oxygen-induced down-regulation of vascular endothelial growth factor was accompanied by an increase in astrocyte-derived fibroblast growth factor-2. Therefore, PDGF-A increases retinal astrocytes, which promote the survival of endothelial cells as well as their expression of barrier characteristics.

Animals↗
PubMed2000

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.

Retinal vasculogenesis and ischemic retinopathies provide good model systems for study of vascular development and neovascularization (NV), respectively. Vascular endothelial cell growth factor (VEGF) has been implicated in the pathogenesis of retinal vasculogenesis and in the development of retinal NV in ischemic retinopathies. However, insulin-like growth factor-I and possibly other growth factors also participate in the development of retinal NV and intraocular injections of VEGF antagonists only partially inhibit retinal NV. One possible conclusion from these studies is that it is necessary to block other growth factors in addition to VEGF to achieve complete inhibition of retinal NV. We recently demonstrated that a partially selective kinase inhibitor, PKC412, that blocks phosphorylation by VEGF and platelet-derived growth factor (PDGF) receptors and several isoforms of protein kinase C (PKC), completely inhibits retinal NV. In this study, we have used three additional selective kinase inhibitors with different selectivity profiles to explore the signaling pathways involved in retinal NV. PTK787, a drug that blocks phosphorylation by VEGF and PDGF receptors, but not PKC, completely inhibited retinal NV in murine oxygen-induced ischemic retinopathy and partially inhibited retinal vascularization during development. CGP 57148 and CGP 53716, two drugs that block phosphorylation by PDGF receptors, but not VEGF receptors, had no significant effect on retinal NV. These data and our previously published study suggest that regardless of contributions by other growth factors, VEGF signaling plays a critical role in the pathogenesis of retinal NV. Inhibition of VEGF receptor kinase activity completely blocks retinal NV and is an excellent target for treatment of proliferative diabetic retinopathy and other ischemic retinopathies.

Aging↗
PubMed2000

Experimental models of growth factor-mediated angiogenesis and blood-retinal barrier breakdown.

Following chronic ischemia, vascular endothelial growth factor (VEGF) is induced primarily in the ganglion cell layer of the retina. This often results in neovascularization (NV) that originates from the vascular bed closest to the ganglion cell layer. To study the effects of VEGF, independent lines of transgenic mice that express VEGF in the lens and in the retina have been generated. Expression in the lens results in excessive proliferation and accumulation of angioblasts and endothelial cells in proximity to the lens. However, VEGF expression is not sufficient to direct blood vessel organization or maturation in the prenatal mouse. Abnormal vessels do form on the retinal surface, but not until the second postnatal week. In transgenic mice expressing VEGF in the photoreceptors, NV originates from the deep capillary bed--the vascular bed closest to the photoreceptors. NV is accompanied by localized blood-retinal barrier breakdown. NV is also induced in PDGF-B transgenic mice. PDGF-B expression in the lens occurs prenatally and, during this time, mainly affects the perilenticular vessels. Postnatally, transgenic mice expressing PDGF-B in the lens or photoreceptors show a similar phenotype. In both models, a highly vascularized cell mass containing endothelial cells, pericytes, and glia forms in the superficial retina, and the formation of the deep capillary bed is inhibited. The phenotype suggests that an additional factor is necessary for the maturation and penetration of vascular endothelial cells into the retina to form the deep capillary bed.

Animals↗
PubMed2000

Purification and characterization of iron superoxide dismutase and copper-zinc superoxide dismutase from Acanthamoeba castellanii.

Two superoxide dismutases (SOD I and SOD II) were purified from Acanthamoeba castellanii and characterized for several biochemical properties. Analysis of the primary structure and inhibition studies revealed that SOD I is iron SOD (Fe-SOD), with a molecular mass of 50 kDa, and SOD II is copper-zinc SOD (Cu,Zn-SOD), with a molecular mass of 38 kDa. Both enzymes have a homodimeric structure consisting of 2 identical subunits, each with a molecular mass of 26 and 19 kDa for SOD I and SOD II, respectively. The isoelectric points of SOD I and SOD II were 6.4 and 3.5, respectively, and there were no isoenzyme forms detected. Both enzymes show a broad optimal pH of 7.0-11.0. Because no differences were observed in the apparent molecular weight of SOD I after addition of the reducing agent 2-mercaptoethanol, the subunits do not appear to be linked covalently by disulfide bonds. However, the subunits of SOD II were covalently linked by intra- and interdisulfide bonds. Western blot analyses showed that the 2 enzymes have different antigenicity. Both enzymes occur as cytoplasmic and detergent-extractable fractions. These enzymes may be potential virulence factors of A. castellanii by acting both as antioxidants and antiinflammatory agents. These enzymes may be attractive targets for chemotherapy and immunodiagnosis of acanthamoebiasis.

Acanthamoeba↗
PubMed2000

Axial length in branch retinal vein occlusion.

To determine the effects of axial length on the development of branch retinal vein occlusion (BRVO), determination of the affected eye, development of surgical complications, and visual prognosis, axial length was measured in 27 eyes each in surgical, non-surgical and control group and in 54 eyes each in occlusion (surgical + non-surgical group), non-affected eye (non-affected eyes of occlusion group), and non-occlusion group (both eyes of the control group). The average axial length was 22.61 mm in surgical, 22.48 mm in non-surgical, 23.09 mm in control, 22.55 mm in occlusion, 22.56 mm in non-affected eye, and 23.11 mm in non-occlusion group. The axial length showed a statistically significant difference between surgical and control group (p = 0.018), between non-surgical and control group (p = 0.002), and between occlusion and non-occlusion group (p < 0.001); however, no statistically significant difference was seen between surgical and non-surgical group, between non-affected eyes of surgical and non-surgical group, and between occlusion and non-affected eye group. Also, in such as BRVO groups as surgical, non-surgical, and occlusion groups, no correlation was present between axial length and degree of visual acuity recovery and final visual acuity. Although the possibility of developing BRVO is higher in those with short axial length, the axial length may have no relationship with the determination of the affected eye, visual prognosis and development of surgical complications.

Adult↗
PubMed2000

Management of posteriorly dislocated intraocular lens using pars plana vitrectomy.

In order to evaluate the results of pars plana vitrectomy (PPV) for the treatment of posteriorly dislocated intraocular lens (PC-IOL), we retrospectively examined and analyzed the hospital records of patients who had undergone PPV to exchange or reposition a PC-IOL dislocated into the vitreous cavity. Of 20 eyes in 20 patients, IOL exchange was performed in 6 eyes, and IOL repositioning in 14 eyes. Posteriorly dislocated IOL occurred in 14 eyes during or within 2 days, and in 6 eyes 6 months after the IOL implantation. Thirteen eyes were surgically treated early after the occurrence, within 3 days, while 7 eyes were treated later, between 5 to 7 days. Compared with preoperative best-corrected visual acuity, the final visual acuity improved more than 2 lines in 12 eyes. With no significant difference on the statistics, earlier visual rehabilitation seemed to be shown in late-treated patients than in early-treated. Accordingly, a posterior dislocation of IOL can be successfully treated with PPV, and barring any serious complications such as retinal detachment, there is no need for surgery immediately following the occurrence.

Adolescent↗
PubMed1999

Rapid degradation of PrxI and PrxII induced by silica in Rat2 cells.

Peroxidases of the peroxiredoxin (Prx) family catalyze the reduction of H(2)O(2) and lipid peroxides. The effects of H(2)O(2), 12-O-tetradecanoylphorbol 13-acetate (TPA), and silica on the abundance of two cytosolic isoforms of Prx (PrxI and PrxII) were examined in Rat2 cells. TPA induces the production of reactive oxygen species (ROS) in various mammalian cell types, and silica induces the production of ROS in Rat2 cells. Whereas H(2)O(2) and TPA did not affect the concentration of PrxI or Prx II, silica triggered a rapid degradation of both Prx enzymes. Silica also induced degradation of the NF-kappaB inhibitor IkappaB-alpha. N-Acetylcysteine and diphenyleneiodonium, both of which inhibit the accumulation of intracellular ROS, each blocked silica-induced degradation of IkappaB-alpha but had no effect on that of the Prx enzymes, suggesting that ROS do not contribute to Prx proteolysis. The silica-induced degradation of Prx enzymes was also insensitive to the proteasome inhibitors MG132 and lactacystin, whereas IkappaB-alpha proteolysis was completely blocked by these inhibitors. Experiments with the Ca(2+) ionophore A23187 indicated that a Ca(2+)-dependent protease such as calpain might contribute substantially to silica-induced degradation of PrxII, but only moderately to that of PrxI. These results indicate that silica increases cellular oxidative stress not only by inducing ROS production, but also by triggering the degradation of Prx enzymes that are responsible for elimination of cellular ROS. Such aggravated oxidative stress might be important in the initial pathogenesis of silica-associated pulmonary diseases.

Animals↗