Peroxiredoxin I regulates the component expression of gamma-secretase complex causing the Alzheimer's disease / 한국실험동물학회지

Peroxiredoxin I (Prx I) is a member of the peroxiredoxins (Prxs) family, which are antioxidant enzymes that regulate various cellular process via intracellular oxidative signal pathways. In order to investigate the correlation between Prx I and the gamma-secretase complex, which causes Alzheimer's disease (AD), the expression level of Prx I was firstly evaluated in an animal model for AD. NSE/hPen-2 transgenic (Tg) mice, which were used as animal model in this study, showed a high level of Pen-2 expression and accumulation of Abeta-42 peptides in the hippocampus of brain. The expression level of Prx I was significantly higher on the mRNA and protein level in the brain of this model, while not change in Prx VI expression was observed. Furthermore, to verify the effect of Prx I on the gamma-secretase components in vitro, the expression level of these components was analyzed in the Prx I transfectants. Of the components of the gamma-secretase complex, the expression of PS-2 and Pen-2 was lower in the transfectants overexpressing Prx I compared to the vector transfectants. However, the expression of APP, NCT and APH-1 did not change in Prx I transfectants. Therefore, these results suggested that the expression of Prx I may be induced by the accumulation of Abeta-42 peptides and the overexpression of Prx I in neuroblastoma cells may regulate the expression of gamma-secretase components.

Expression of Peroxiredoxin I in the Epidermis of Vitiligo / 대한피부과학회지

BACKGROUND: Although the pathogenesis of vitiligo isn't fully understood, a recent study demonstrates that oxidative stress plays an important role to induce vitiligo. Peroxiredoxin (Prx) is a novel peroxidase family to remove hydrogen peroxide using thioredoxin system, which is consisted of thioredoxin, thioredoxin reductase, and NADPH. OBJECTIVE: This study aimed to investigate the change of expression of Prx I to elucidate the role of oxidative stress in the pathogenesis of vitiligo. METHODS: Sample specimens were obtained from the lesional skin of vitiligo patients, and non-depigmented skin was obtained from the perilesional area as control samples. The skin samples were immediately frozen using liquid nitrogen, and then section samples were prepared to perform immunohistochemical staining with antibodies for Prx I. Some of the skin biopsy samples were used for primary culture of keratinocytes. Protein extracts from the expanded keratinocytes were prepared for Western blot analysis of Prx I. RESULTS: In vitiligo, the ubiquitous expression of Prx I in all layers of epidermis, which was also observed in the normal perilesional skin, was reduced in the depigmented lesion of vitiligo patients. The reduction of Prx I was remarkable from the lesions which were exposed to sunlight. Consistently, Prx I expression from the lesional keratinocytes were noticeably reduced in comparison with that from perilesional keratinocytes. CONCLUSION: Our results showing that Prx I is impaired in the epidermis of depigmented lesions of vitiligo patients suggest that oxidative stress is an important factor to induce vitiligo.

Analysis of the Expression of Peroxiredoxin I in Human Bladder Cancer / 대한비뇨기과학회지

PURPOSE: Peroxiredoxins(PRDXs) are antioxidant enzymes that play an important role on cell differentiation, proliferation and apoptosis. In this study, we investigated if the expression levels of PRDX I were related to bladder cancer. MATERIALS AND METHODS: The mRNA level of PRDX I was examined via real time polymerase chain reaction(PCR) in 186 cancer specimens from patients with primary bladder cancer, 73 corresponding samples of normal looking bladder mucosae surrounding the cancer and 21 samples of normal bladder mucosae. We investigated the correlation between the expression levels of PRDX I and the clinico-pathological parameters of the 154 patients who could be followed up more than three years. RESULTS: The expression levels of PRDX I in bladder cancer(0.73pg/ml) were significantly higher that that in the normal bladder mucosae (0.04 pg/ml)(p<0.01) or that in the corresponding normal bladder mucosae surrounding the cancer(0.38pg/ml)(p<0.01). The expression level of PRDX I was not significantly enhanced in the non-recurred(0.87pg/ml) superficial bladder tumor patients compared with the recurred superficial bladder tumor patients(0.63pg/ml), but it was significantly enhanced in the non-progressed(0.82pg/ml) patients compared with the progressed (0.50pg/ml) patients(p<0.05 for each). CONCLUSIONS: An enhanced expression of PRDX I is strongly associated with the development of bladder cancer. Moreover, enhanced expressions of PRDX I are also positively associated with a low rate of progression of bladder cancer, and this might be useful as a marker for assessing progression in human bladder cancers.

The Inhibition of Human Telomerase Reverse Transcriptase Expression by Peroxiredoxin I and c-Myc in Prostatic Cancer Cells / 대한비뇨기과학회지

PURPOSE: We evaluated the hypothesis that the telomerase expression is associated with c-Myc and peroxiredoxin I (Prx I) in patients with prostate cancer. The study determined the link between Prx I, c-Myc and human telomerase reverse transcriptase (hTERT) in prostate cancer cells. MATERIALS AND METHODS: The cDNA of the Prx I gene was obtained by reverse-transcriptase polymerase chain reaction (RT-PCR) amplification. Cotransfections were performed by using a hTERT luciferase reporter plasmid and each expression vector as indicated (c-Myc or Prx I). Empty vectors were used as controls for determining the basal promoter activity. RT-PCR was performed to evaluate the effect of the DEM-induced Prx I mRNA expression. Luciferase assay was performed to evaluate the inhibitory effect of transfected Prx I and the DEM induced Prx I on the transcriptional activity of hTERT in the human prostatic cancer cell lines PC-3 and DU-145. RESULTS: In this study, we found that Prx I could inhibit hTERT expression through direct interaction with c-Myc protein in the prostate cancer cell lines. In addition, it was obvious that Prx I could interact with c-Myc protein. We also found that DEM could induce upregulation of the Prx I mRNA expression and that the increased expression of Prx I could downregulate the expression of hTERT. CONCLUSIONS: Our results demonstrated a direct link between Prx I, c-Myc and hTERT, and we suggest that Prx I regulates cellular immortalization through c-Myc and hTERT, which is activation step in carcinogenesis.

Modulation of Peroxiredoxin I Expression by UVB Irradiation in Human Keratinocytes: H2O2-mediated Modulation of Peroxiredoxin I / 대한피부과학회지

BACKGROUND: Peroxiredoxin I (Prx I) is part of an oxidative stress defense system with thioredoxin peroxidase activity to eliminate hydrogen peroxide (H2O2). UV irradiation is one of the major sources to produce H2O2, which should then be scavenged by antioxidant systems to maintain functional integrity of the skin. OBJECTIVE: This study aimed to evaluate the modulation of Prx I by ultraviolet B (UVB) irradiation in human epidermal keratinocytes. The modulation of Prx I expression by H2O2 was also evaluated. METHOD: Primary culture of epidermal keratinocytes was performed, and sub-confluent cells were irradiated with UVB irradiation (20mJ/cm(2)). Western blot and Northern blot analysis were performed after the cells were harvested at different time-points after UVB irradiation. Prx I expression and intracellular levels of H2O2 were evaluated in the cells which had been irradiated with different doses of UVB. The localization of Prx I expression was identified by immunocytochemical staining. RESULTS: UVB irradiation induced Prx I mRNA and protein expressions from 3 h and 6 h after irradiation, respectively, indicating that UVB induced Prx I expression at a transcription level. Intracellular H2O2 levels were steadily increased as keratinocytes were irradiated with increasing doses of UVB. Next, when keratinocytes were treated with 0.1-10.0mM of H2O2, the marked induction of Prx I protein expression was observed above 1 mM H2O2 at a time-dependent manner (after 6 h). The H2O2-induced Prx I expression was abolished by N-acetyl-L-cysteine, a H2O2 scavenger, pre-treatment. In 2D-gel electrophoresis, the active reduced form of Prx I was rapidly transformed into the oxidized, inactive form, and then it restored to the reduced form by H2O2 treatment, suggesting that Prx I was active in responding to the H2O2-induced oxidative stress. CONCLUSION: UVB irradiation up-regulates Prx I by the mediation of H2O2 in the keratinocytes.