RESUMO
BACKGROUND: Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. METHODSâANDâRESULTS: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXRα) expression were downregulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXRα expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXRα expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPPs-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages. CONCLUSIONS: AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXRα signaling pathway in apoE-KO mice.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/biossíntese , Produtos da Oxidação Avançada de Proteínas/metabolismo , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Regulação para Baixo , Metabolismo dos Lipídeos , Lipoproteínas/biossíntese , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Produtos da Oxidação Avançada de Proteínas/genética , Animais , Aterosclerose/genética , Lipoproteínas/genética , Masculino , Camundongos , Camundongos KnockoutRESUMO
Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis. In recent years, it has been demonstrated that NgBR plays an important role in human pathophysiological processes, including lipid metabolism, angiogenesis, N-glycosylation, cell apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial-mesenchymal transition. The pathophysiologic effects of NgBR have garnered increased attention, and the detection and enhancement of NgBR expression may be a novel approach to monitor the development and to improve the prognosis of relevant human clinical diseases.
Assuntos
Metabolismo dos Lipídeos , Proteínas Nogo/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Apoptose , Proteínas de Transporte/metabolismo , Proliferação de Células , Fosfatos de Dolicol/metabolismo , Glicoproteínas/metabolismo , Glicosilação , Humanos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Fisiológica , Doença de Niemann-Pick Tipo C/metabolismo , Receptores Nogo/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Transporte VesicularRESUMO
OBJECTIVES: To determine the expression of nitric oxide synthase (NOS) in testis and to investigate the effects of NO on the reproductive function of testis. METHODS: Testes of adult male Sprague-Dawley rats were fixed in 4% paraformaldehyde. The paraffin sections were made as routine. Immunohistochemical ABC method was used to observe the localization of NOS. RESULTS: Endothelia NOS (eNOS), neuronal NOS (nNOS) and inductive NOS (iNOS) were all expressed in Leydig cells. Only eNOS was expressed in peritubular myoid cells, endothelial and smooth muscle cells of blood vessel, while only nNOS expressed in tunica adventitia of testicular blood vessels. The reactive substance distributes in cytoplasm with negative nuclei. Immunoreactivity for eNOS, nNOS and iNOS in all spermatogenic cells was negative. CONCLUSIONS: Three kinds of NOS were all expressed in testis and the distribution of different NOS had a little difference.
Assuntos
Óxido Nítrico Sintase/análise , Testículo/enzimologia , Animais , Imuno-Histoquímica , Masculino , Óxido Nítrico/biossíntese , Ratos , Ratos Sprague-DawleyRESUMO
The definite molecular mechanisms underlying the genesis of nasopharyngeal carcinomas (NPCs) remain to be completely elucidated. miRNAs are small non-coding RNAs which are implicated in cell proliferation, apoptosis, and even carcinogenesis through negatively regulating gene expression post-transcriptionally. EBV was the first human virus found to express miRNAs. EBV-encoded BART-miRNAs and dysregulated cellular miRNAs are involved in carcinogenesis of NPC by interfering in the expression of viral and host cell genes related to immune responses and perturbing signal pathways of proliferation, apoptosis, invasion, metastasis and even radio-chemo-therapy sensitivity. Additional studies on the roles of EBV-encoded miRNAs and cellular miRNAs will provide new insights concerning the complicated gene regulated network and shed light on novel strategies for the diagnosis, therapy and prognosis of NPC.
Assuntos
Proteínas de Transporte/genética , Herpesvirus Humano 4/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Animais , Carcinoma , Humanos , Carcinoma NasofaríngeoRESUMO
STGC3 is a potential tumor suppressor that inhibits the growth of the nasopharyngeal carcinoma cell line CNE2; the expression of this protein is reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue. In this study, we investigated the tumor-suppressing activity of STGC3 in nude mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an increase in Bax protein expression. A proteomic approach was used to assess the protein expression profile associated with STGC3-mediated apoptosis. Western blotting confirmed the differential up-regulation of prohibitin seen in proteomic analysis. These results indicate that overexpression of STGC3 inhibits xenograft growth in nude mice by enhancing apoptotic cell death through altered expression of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data contribute to our understanding of the function of STGC3 in human nasopharyngeal carcinoma and provide new clues for investigating other STGC3-associated tumors.
RESUMO
AIM: To investigate the effect of ciglitazone on CD36 expression and cholesterol influx in THP-1 macrophage. METHODS: After exposure of the cultured THP-1 macrophage to ciglitazone for 24 h, [(3)H] labeled Cholesterol influx was determined by FJ-2107P typed liquid scintillator. CD36 mRNA and protein level were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting respectively. RESULTS: PPARγ agonist, ciglitazone, elevated CD36 in both protein and mRNA levels, and increased cholesterol influx in THP-1 macrophage. The levels of cholesterol influx were 20. 3%, 28. 6%, 37. 2%, 44. 3%, 48. 7% respectively. CONCLUSION: Our results indicated that ciglitazone may play an important role in cholesterol influx and modulating CD36 expression in THP-1 macrophage.
Assuntos
Antígenos CD36/metabolismo , Colesterol/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Tiazolidinedionas/farmacologia , Antígenos CD36/efeitos dos fármacos , Linhagem Celular , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Humanos , Masculino , PPAR gama/agonistas , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismoRESUMO
STGC3 is a potential tumor suppressor that inhibits the growth of the nasopharyngeal carcinoma cell line CNE2; the expression of this protein is reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue. In this study, we investigated the tumor-suppressing activity of STGC3 in nude mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an increase in Bax protein expression. A proteomic approach was used to assess the protein expression profile associated with STGC3-mediated apoptosis. Western blotting confirmed the differential up-regulation of prohibitin seen in proteomic analysis. These results indicate that overexpression of STGC3 inhibits xenograft growth in nude mice by enhancing apoptotic cell death through altered expression of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data contribute to our understanding of the function of STGC3 in human nasopharyngeal carcinoma and provide new clues for investigating other STGC3-associated tumors.