Cellular stress and redox activity proteins are involved in gastric carcinogenesis associated with Helicobacter pylori infection expressing high levels of thioredoxin-1 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Helicobacter pylori infection is related to the development of gastric diseases. Our previous studies showed that high thioredoxin-1 (Trx1) expression in H. pylori can promote gastric carcinogenesis. To explore the underlying molecular mechanisms, we performed an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis of stomach tissues from Mongolian gerbil infected with H. pylori expressing high and low Trx1. Differences in the profiles of the expressed proteins were analyzed by bioinformatics and verified using Western blot analysis. We found three candidate proteins, 14-3-3α/β, glutathione-S-transferase (GST), and heat shock protein 70 (HSP70), in high Trx1 tissues compared with low Trx1 tissues and concluded that cellular stress and redox activity-related proteins were involved in the pathogenesis of gastric cancer associated with H. pylori Trx1.

Relationship between TRX1 and JAB1 in acute myelogenous leukemia / 西安交通大学学报(医学版)

ABSTRACT:Objective To detect the expressions of thioredoxin (TRX1)and c-jun-activation-domain binding protein-1 (JAB1)in patients with acute myelogenous leukemia (AML)and healthy controls,and measure the TRX1 level in AML patients at different stages for evaluating its clinical significance.Methods The expressions of TRX1 and JAB1 in leukemia samples were analyzed by RT-PCR and Western blot at mRNA and protein levels, respectively.The correlation between TRX1 and JAB1,and the relationship between the gene expression and peripheral blood leukocytes count were also analyzed.Furthermore,serum TRX1 was measured by ELISA.Results TRX1 and JAB1 expressions at both mRNA and protein levels were obviously upregulated in leukemia patients (P<0.05). TRX1 was positively related to JAB1 in both newly diagnosed and recurrent AML patients.And high levels of TRX1 and JAB1 expressions were associated with white blood cell (WBC)counts in AML patients (P<0.05).Moreover, abundance of TRX1 in serum was significantly greater in AML patients,especially in the patients with recurrent AML,than in healthy donors (P<0.05).Conclusion There is a positive correlation between the expressions of TRX1 and JAB1 ,which is closely related to the occurrence and progression of AML.

Inhibición de la hipertrofia ventricular izquierda, normalización de la respuesta contráctil cardíaca y estrés oxidativo en hipertensión experimental / Inhibition of Left Ventricular Hypertrophy, Normalization of the Contractile Response and Oxidative Stress in Experimental Hypertension

Introducción y objetivos: La hipertrofia ventricular izquierda secundaria a hipertensión arterial se ha interpretado como un mecanismo de protección para reducir el estrés parietal y prevenir la insuficiencia cardíaca. Sin embargo, paradójicamente, su presencia se acompaña de un incremento de la morbimortalidad cardiovascular. El presente estudio se llevó a cabo con el propósito de evaluar si el tratamiento antihipertensivo crónico inhibe el desarrollo de hipertrofia ventricular izquierda y revierte el deterioro de la respuesta betaadrenérgica cardíaca y su posible relación con cambios en el metabolismo oxidativo del miocardio. Material y métodos: Ratas macho espontáneamente hipertensas (REH, 2 meses de edad) se distribuyeron en grupos (n grupo = 18) grupo según (mg/kg, v.o.): losartán 30 (L), hidralazina 11 (H), rosuvastatina 10 (R), carvedilol 20 (C), agua (control tratamiento). Control hipertensión: 18 ratas normotensas (Wistar-Kyoto, WKY). Periódicamente se registraron la presión arterial sistólica (PAS) (pletismografía, en animales despiertos) y el peso corporal (PC). Luego de 16 meses se practicó eutanasia. El 50% de los corazones se montaron en preparación de Langendorff para medir contractilidad preestímulo y posestímulo betaadrenérgico [isoproterenol (Iso): 10-9M, 10-7M, 10-5M]. En los corazones restantes se registró el peso del ventrículo izquierdo (PVI), que se normalizó por el PC. Se cuantificó la expresión inmunohistoquímica de tiorredoxina 1(Trx-1), peroxirredoxina 2 (Prx-2) y glutarredoxina 3 (Grx-3) (indicadores antioxidantes). Resultados: Peso corporal: similar en todos los grupos. PAS (mm Hg): 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (REH)*, 183 ± 1 (C)**, 141 ± 1 (WKY) (*p < 0,05 vs. L, H, WKY; **p < 0,05 vs. L, H, WKY, REH). El PVI/PC de REH y R fue mayor (p < 0,05) respecto de L, H, C y WKY. En C no se observó correlación entre hipertensión e hipertrofia ventricular izquierda. Grupos REH, R y C: mostraron depresión de contractilidad basal vs. L, H y WKY. Respuesta a Iso 10-5 M: similar en WKY y L; disminuida en C, H, R y REH. Expresión de Trx-1, Prx-2 y Grx-3: aumentó en C, H, R y L (1,5-2 veces promedio; p < 0,01 vs. REH y WKY). Conclusiones: El tratamiento con losartán, hidralazina y carvedilol previno el desarrollo de hipertrofia ventricular izquierda. El losartán normalizó la respuesta al isoproterenol en REH. Factores adicionales participarían en el desarrollo de hipertrofia ventricular izquierda con deterioro de la respuesta inotrópica a la estimulación betaadrenérgica en hipertensión. El aumento en la expresión de tiorredoxinas por tratamientos antihipertensivos sugiere un beneficio asociado, aumentando la respuesta antioxidante frente al estrés oxidativo en hipertensión.

Background and objectives: Left ventricular hypertrophy secondary to hypertension has been perceived as a protective mechanism to reduce wall stress and prevent heart failure. However, its presence is paradoxically associated with increased cardiovascular morbidity and mortality The aim of this study was to evaluate whether chronic antihypertensive treatment inhibits the development of left ventricular hypertrophy and normalize the reverting impaired cardiac beta-adrenergic response, and its possible association with changes in myocardial oxidative metabolism. Methods: Spontaneously hypertensive male rats (SHR, 2 months old) were divided into groups (n grupo = 18) according to (mg/ group kg, p.o): losartan 30 (L), hydralazine-11 (H), rosuvastatin 10 (R), carvedilol 20 (C), and water (control treatment). The control hypertension group consisted of 18 normotensive rats (Wistar-Kyoto, WKY). Systolic blood pressure (SBP) (plethysmography in awake animals) and body weight (BW) were measured periodically. The animals were sacrificed at 16 months and 50% of the hearts were mounted in a Langendorff system to measure contractility before and after beta-adrenergic stimulation [isoproterenol (Iso): 10-9 M, 10-7 M, and 10-5 M]. In the remaining hearts left ventricular weight (LVW) was measured and normalized by B W. Immunohistochemical expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2) and glutaredoxin 3 (Grx-3) (antioxidant indicators) was quantified. Results: Body weight was similar in all groups. Systolic blood pressure (mm Hg) was 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (SHR)*, 183 ± 1 (C)**, and 141 ± 1 (WKY) (* p < 0.05 vs. L, H, WKY, ** p < 0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p < 0.05) compared with L, H, C and WKY. In C, there was no correlation between hypertension and left ventricular hypertrophy. SHR, R and C evidenced baseline contractile depression vs. L, H and WKY. The response to 10-5 M Iso was similar in WKY and L, and reduced in C, H, R and SHR. The expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (average increase: 1.5-2 times; p < 0.01 vs. SHR and WKY). Conclusions: Treatment with losartan, hydralazine, and carvedilol prevented the development of left ventricular hypertrophy. Losartan normalized the response to isoproterenol in SHR. Additional factors might participate in the development of left ventricular hypertrophy with impaired inotropic response to beta-adrenergic stimulation in hypertension. The increased ex-pression of thioredoxins as a result of antihypertensive treatment suggests an additional benefit, increasing the antioxidant response against oxidative stress in hypertension.

Inhibition of probucol on the apoptosis of vascular smooth muscle cell induced by hydrogen peroxide / 中国药理学通报

Aim To investigate the effects of antioxidant probucol on vascular smooth muscle cells(VSMCs) apoptosis induced by H2O2.Methods H2O2 (1 mmol?L-1) was used to induce VSMCs apoptosis.The VSMCs were treated with probucol(100,10,1 ?mol?L-1) for 6 hours.For the evaluation of apoptosis,Annexin V-FITC staining,Hoechest33258 staining and the TUNEL assay were used.The expressions of ASK-1 and Trx-1 were detected by Western blot analysis.Results H2O2 could promote the apoptosis of VSMCs,increase the expression of ASK-1 and decrease the expression of Trx-1.Probucol could attenuate the apoptosis induced by H2O2 in a dose-dependent,down-regulate ASK-1 expression and increase Trx-1 expression.Conclusion Probucol can antagonize the apoptosis of VSMCs induced by H2O2.The mechanism may be correlated with a decreased expression of ASK-1 and an increased expression of Trx-1.