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1.
Vaccine X ; 17: 100437, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38317857

RESUMEN

The mumps virus (MuV) causes a highly contagious human disease characterized by swelling of the parotid glands. Although the administration of an attenuated Jeryl Lynn (JL) MuV vaccine shows efficacy in reducing the incidence of MuV infection, sporadic mumps outbreaks still occur in vaccinated populations. We have previously established that an inactivated F genotype mumps vaccine has a higher neutralizing antibody titer against diverse circulating mumps viruses in mice. Here, we aimed to develop a vaccination strategy to enhance the immune response for MuV and assess the effects of heterologous vaccination compared with homologous approaches. We administered an inactivated F genotype mumps vaccine booster following a homologous prime-boost regime and compared its efficacy with three doses of homologous JL vaccine in mice. We demonstrated robust stimulation of neutralizing antibodies and cellular immune response of interferon-γ-secreting cytotoxic T cells following administration of an inactivated F genotype mumps vaccine booster after a homologous prime-boost regime with JL. Compared with the homologous prime-boost regime, this heterologous prime-boost regime showed protective efficacy against the F genotype of MuV. These findings suggest that the heterologous vaccination strategy based on the administration of an inactivated F genotype mumps vaccine provides more effective cross-protection against circulating wild-type mumps viruses than homologous vaccination.

2.
Vaccines (Basel) ; 12(6)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38932324

RESUMEN

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar-/- mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics.

3.
Biochem Soc Trans ; 41(6): 1489-94, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24256242

RESUMEN

Autophagy is a highly conserved cytoplasmic degradation pathway that has an impact on many physiological and disease states, including immunity, tumorigenesis and neurodegeneration. Recent studies suggest that autophagy may also have important functions in embryogenesis and development. Many autophagy gene-knockout mice have embryonic lethality at different stages of development. Furthermore, interactions of autophagy with crucial developmental pathways such as Wnt, Shh (Sonic Hedgehog), TGFß (transforming growth factor ß) and FGF (fibroblast growth factor) have been reported. This suggests that autophagy may regulate cell fate decisions, such as differentiation and proliferation. In the present article, we discuss how mammalian autophagy may affect phenotypes associated with development.


Asunto(s)
Autofagia , Embrión de Mamíferos/citología , Animales , Diferenciación Celular , Proliferación Celular , Humanos , Fenotipo
4.
Vaccines (Basel) ; 11(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36679951

RESUMEN

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.

5.
Neuron ; 111(13): 2021-2037.e12, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37105172

RESUMEN

In neurodegenerative diseases, microglia switch to an activated state, which results in excessive secretion of pro-inflammatory factors. Our work aims to investigate how this paracrine signaling affects neuronal function. Here, we show that activated microglia mediate non-cell-autonomous inhibition of neuronal autophagy, a degradative pathway critical for the removal of toxic, aggregate-prone proteins accumulating in neurodegenerative diseases. We found that the microglial-derived CCL-3/-4/-5 bind and activate neuronal CCR5, which in turn promotes mTORC1 activation and disrupts autophagy and aggregate-prone protein clearance. CCR5 and its cognate chemokines are upregulated in the brains of pre-manifesting mouse models for Huntington's disease (HD) and tauopathy, suggesting a pathological role of this microglia-neuronal axis in the early phases of these diseases. CCR5 upregulation is self-sustaining, as CCL5-CCR5 autophagy inhibition impairs CCR5 degradation itself. Finally, pharmacological or genetic inhibition of CCR5 rescues mTORC1 hyperactivation and autophagy dysfunction, which ameliorates HD and tau pathologies in mouse models.


Asunto(s)
Enfermedad de Huntington , Enfermedades Neurodegenerativas , Ratones , Animales , Microglía/metabolismo , Transducción de Señal , Autofagia , Enfermedades Neurodegenerativas/metabolismo , Proteínas/metabolismo , Enfermedad de Huntington/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo
6.
PLoS One ; 18(12): e0295594, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38060612

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.


Asunto(s)
COVID-19 , Vacunas de ADN , Humanos , Animales , Ratones , SARS-CoV-2/genética , COVID-19/prevención & control , Pandemias , Vacunación , Anticuerpos Neutralizantes , Inmunoglobulina G , Anticuerpos Antivirales
7.
Vaccine ; 41(11): 1892-1901, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36792434

RESUMEN

Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , Animales , Ratones , Anticuerpos Neutralizantes , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus , Virus del Sarampión/genética , Anticuerpos Antivirales , COVID-19/prevención & control , Vacuna Antisarampión
8.
Hepatology ; 54(5): 1661-78, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21748762

RESUMEN

UNLABELLED: Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival. CONCLUSIONS: These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Cisplatino/farmacología , Ciclofilinas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Ciclofilinas/metabolismo , Resistencia a Antineoplásicos/fisiología , Femenino , Células Hep G2 , Humanos , Peróxido de Hidrógeno/farmacología , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Oxidantes/farmacología , Regiones Promotoras Genéticas/fisiología , Factor de Transcripción STAT3/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
9.
J Virol Methods ; 306: 114540, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35550887

RESUMEN

Japanese encephalitis is prevalent throughout the temperate and tropical regions of Asia and is caused by the Japanese encephalitis virus (JEV), a mosquito-borne viral pathogen. The plaque reduction neutralization test (PRNT) is currently recommended as the gold standard test for detecting human antibodies against JEV. The plaque assay is the most widely used method for detecting infectious virions and involves counting discrete plaques in cells. However, it is time-consuming, and results can be subjective (owing to analyst variability during manual plaque counting). The focus reduction neutralization test (FRNT), which is based on an immuno-colorimetric assay, can be used to automatically count foci formed by the JEV. Here, we compared the efficacy of PRNT and FRNT in measuring the neutralizing antibody titers using 102 serum samples from vaccinated and unvaccinated individuals. We observed positive correlations between these neutralization assays against the Nakayama and Beijing strains (R2 = 0.98 and 0.77, respectively). Thus, FRNT may be preferable to PRNT for evaluating the efficacy of JEV vaccines in large-scale serological studies.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Virus de la Encefalitis Japonesa (Subgrupo) , Encefalitis Japonesa , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Encefalitis Japonesa/diagnóstico , Humanos , Pruebas de Neutralización/métodos , Ensayo de Placa Viral
10.
Cell Physiol Biochem ; 28(5): 873-86, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22178940

RESUMEN

Mitochondrial oxidative damage is thought to play a key role in pancreatic ß-cell failure in the pathogenesis of type 2 diabetes. Despite this, the potential of mitochondria-targeted antioxidants to protect pancreatic ß-cells against oxidative stress has not yet been studied. Therefore, we investigated if mitochondria-targeted antioxidants protect pancreatic ß-cells such as RINm5F and HIT-T15 cells against oxidative stress under glucotoxic and glucolipotoxic conditions. When ß-cells were incubated under these conditions, the expression levels of mitochondrial electron transport chain complex subunits, mitochondrial antioxidant enzymes (such as MnSOD and Prx3), ß-cell apoptosis, lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, mitochondrial membrane depolarization, nuclear NF- κB and sterol regulatory element binding protein 1c (SREBP1c) were all increased, in parallel with decreases in intracellular ATP content, citrate synthase enzymatic activity and glucose-stimulated insulin secretion. These changes were consistent with elevated mitochondrial oxidative stress, and incubation with the mitochondria-targeted antioxidants, MitoTempol or Mitoquinone (MitoQ), prevented these effects. In conclusion, mitochondria-targeted antioxidants protect pancreatic ß-cells against oxidative stress, promote their survival, and increase insulin secretion in cell models of the glucotoxicity and glucolipotoxicity associated with Type 2 diabetes.


Asunto(s)
Antioxidantes/farmacología , Glucosa/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Insulina/metabolismo , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Línea Celular , Cricetinae , Proteínas de Homeodominio/metabolismo , Secreción de Insulina , Mitocondrias/metabolismo , Membranas Mitocondriales/efectos de los fármacos , FN-kappa B/metabolismo , Compuestos Organofosforados/farmacología , Ratas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Superóxido Dismutasa/metabolismo , Ubiquinona/farmacología
11.
Br J Nutr ; 106(10): 1544-51, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21676280

RESUMEN

It has been reported that high-fat, high-carbohydrate (HFHC) meals increase oxidative stress and inflammation. We examined whether repeated intake of excess energy in the form of HFHC meals alters reactive oxygen species (ROS) generation and the expression levels of antioxidant enzymes and mitochondrial proteins in mononuclear cells, and to determine whether this is associated with insulin resistance. We recruited healthy lean individuals (n 10). The individuals were divided into two groups: one group (n 5) ingested 10878·4 kJ/d (2600 kcal/d; 55-70 % carbohydrate, 9·5-16 % fat, 7-20 % protein) recommended by the Dietary Reference Intake for Koreans for 4 d and the other group (n 5) ingested a HFHC meal containing 14 644 kJ/d (3500 kcal/d). Then, measurements of blood insulin and glucose levels, together with suppressor of cytokine signalling-3 (SOCS-3) expression levels, were performed in both groups. Also, cellular and mitochondrial ROS levels as well as malondialdehyde (MDA) levels were measured. Expression levels of cytosolic and mitochondrial antioxidant enzymes, and mitochondrial complex proteins were analysed. Repeated intake of HFHC meals induced an increase in homeostasis model of assessment-insulin resistance (HOMA-IR), together with an increase in SOCS-3 expression levels. While a single intake of the HFHC meal increased cytosolic and mitochondrial ROS, repeated intake of HFHC meals reduced them and increased the levels of MDA, cytosolic and mitochondrial antioxidant enzymes, and several mitochondrial complex proteins. Repeated intake of HFHC meals induced cellular antioxidant mechanisms, which in turn increased lipid peroxidation (MDA) and SOCS-3 expression levels, induced hyperinsulinaemia and increased HOMA-IR, an index of insulin resistance. In conclusion, excess energy added to a diet can generate detrimental effects in a short period.


Asunto(s)
Antioxidantes/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Estrés Oxidativo , Adulto , Secuencia de Bases , Western Blotting , Composición Corporal , Cartilla de ADN , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Malondialdehído/metabolismo , Reacción en Cadena de la Polimerasa , Especies Reactivas de Oxígeno/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/metabolismo
12.
Vaccine ; 39(13): 1870-1876, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33642163

RESUMEN

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12-15 months and 4-6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1-2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4-5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.


Asunto(s)
Virus de la Parotiditis , Paperas , Anticuerpos Antivirales , Niño , Preescolar , Humanos , Lactante , Vacuna contra el Sarampión-Parotiditis-Rubéola , Paperas/epidemiología , Paperas/prevención & control , Vacuna contra la Parotiditis , Virus de la Parotiditis/genética , Pruebas de Neutralización , República de Corea
14.
Neuron ; 93(5): 1015-1034, 2017 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-28279350

RESUMEN

Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.


Asunto(s)
Autofagia/fisiología , Lisosomas/metabolismo , Neuronas Motoras/patología , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/terapia , Transducción de Señal/fisiología , Animales , Humanos , Enfermedades Neurodegenerativas/metabolismo , Proteínas/metabolismo
15.
Cancer Res ; 72(16): 4214-24, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22719067

RESUMEN

Arsenic trioxide (As2O3) is used, in current practice, as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). However, the side effects and relatively low efficacy of As2O3 in treating other leukemias have limited its wider use in therapeutic applications. In the present study, we found that the expression of carbonyl reductase 1 (CBR1) affects the resistance to As2O3 in leukemias, including APL; As2O3 upregulated CBR1 expression at the transcriptional level by stimulating the activity of the transcription factor activator protein-1. Moreover, CBR1 overexpression was sufficient to protect cells against As2O3 through modulation of the generation of reactive oxygen species, whereas the attenuation of CBR1 was sufficient to sensitize cells to As2O3. A combination treatment with the specific CBR1 inhibitor hydroxy-PP-Me remarkably increased As2O3-induced apoptotic cell death compared with As2O3 alone, both in vitro and in vivo. These results were confirmed in primary cultured human acute and chronic myeloid leukemia cells, with no significant cell death observed in normal leukocytes. Taken together, our findings indicate that CBR1 contributes to the low efficacy of As2O3 and, therefore, is a rational target for the development of combination chemotherapy with As2O3 in diverse leukemias including APL.


Asunto(s)
Oxidorreductasas de Alcohol/antagonistas & inhibidores , Oxidorreductasas de Alcohol/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Arsenicales/farmacología , Inhibidores Enzimáticos/farmacología , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/enzimología , Óxidos/farmacología , Oxidorreductasas de Alcohol/biosíntesis , Oxidorreductasas de Alcohol/genética , Animales , Apoptosis/efectos de los fármacos , Trióxido de Arsénico , Arsenicales/administración & dosificación , Sinergismo Farmacológico , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/administración & dosificación , Femenino , Técnicas de Silenciamiento del Gen , Células HL-60 , Humanos , Células K562 , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Ratones , Ratones Endogámicos BALB C , NADPH Oxidasas/metabolismo , Óxidos/administración & dosificación , Regiones Promotoras Genéticas , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción AP-1/metabolismo , Células U937 , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Antioxid Redox Signal ; 16(3): 245-61, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-21902453

RESUMEN

AIM: Many studies have reported that the generation of reactive oxygen species (ROS) increases during the differentiation of muscle-derived C2C12 cells. Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against oxidative stress. However, the role of Prx-2 in muscle differentiation has not been investigated. RESULTS: In this study, we demonstrated that Prx-2 expression increases during muscle differentiation and regeneration in response to exogenous H(2)O(2). This increase occurs only in myoblast cell lines because no increase in Prx-2 expression was observed in the NIH3T3, MEF, Chang, or HEK293 cell lines. The antioxidants, N-acetyl L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), both suppressed myogenesis and Prx-2 expression. Moreover, Prx-2 was upregulated at the transcriptional level by NF-κB during the differentiation of muscle-derived C2C12 cells. We also found that inhibition of phosphatidylinositol 3-kinase (PI3K) blocks NF-κB activation and suppresses Prx-2 expression. Interestingly, Prx-2 knockdown increased the expression levels of other antioxidant enzymes, including all of the other Prx family member, thioredoxin-1 (Trx-1) and catalase, but also enhanced the accumulation of endogenous ROS during muscle differentiation. INNOVATION: In this study, we demonstrated for the first time that Prx-2 is unregulated during the muscle differentiation and regeneration. CONCLUSION: Prx-2 is upregulated via the PI3K/NF-κB pathway and attenuates oxidative stress during muscle differentiation and regeneration.


Asunto(s)
Diferenciación Celular , Proteínas de Homeodominio/metabolismo , Músculo Esquelético/fisiología , FN-kappa B/metabolismo , Estrés Oxidativo , Regulación hacia Arriba , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Línea Celular , Femenino , Proteínas de Homeodominio/genética , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Especies Reactivas de Oxígeno/metabolismo , Regeneración , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/fisiología , Transcripción Genética
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