Relationship between Erbin and Bax/Bcl-xL-mediated cell apoptosis during sepsis-induced acute kidney injury in mice / 中华麻醉学杂志

Objective:To evaluate the relationship between Erbin and Bax/Bcl-xL-mediated cell apoptosis during sepsis-induced acute kidney injury in mice.Methods:Thirty-two SPF male wild type C57BL/6 mice, 32 SPF male Erbin (-/-) C57BL/6 mice, aged 6-8 weeks, weighing 20-30 g, were divided into 2 groups ( n=16 each) using the random number table method: wild type sham operation group (WT+ Sham group), wild type sepsis group (WT+ S group), Erbin(-/-) sham operation group (EKO+ Sham group), and Erbin(-/-) sepsis group (EKO+ S group). The sepsis model was established using the moderate cecal ligation and puncture (CLP) in anesthetized animals.The survival rates within 7 days after CLP were recorded.The serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), IL-1β, creatinine (Cr), blood urea nitrogen (BUN) and lactic dehydrogenase (LDH) were determined at 24 h after CLP.Then the renal tissues were taken for assessment of renal injury which was scored and for determination of the apoptosis rate (by TUNEL) and expression of cleaved-caspase-3, Bcl-xL and Bax (by Western blot). Results:Compared with sham operation groups, the survival rates were significantly decreased, the serum concentrations of IL-1β, IL-10, TNF-α, Cr, BUN and LDH, renal injury score and apoptosis rate were increased, the expression of Bax and cleaved-caspase-3 was up-regulated, and the expression of Bcl-xL was down-regulated in sepsis groups ( P<0.05). Compared with WT+ S group, the survival rates were significantly decreased, the serum concentrations of IL-1β, LDH, TNF-α, Cr and BUN and renal injury score were increased, the serum concentration of IL-10 was decreased, the apoptosis rate of renal tissues was increased, the expression of Bax and cleaved-caspase-3 was up-regulated, and the expression of Bcl-xL was down-regulated in EKO+ S group ( P<0.05). Conclusions:Erbin can inhibit Bax/Bcl-xL-mediated cell apoptosis and is involved in endogenous protective mechanism against sepsis-induced acute kidney injury in mice.

Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical Outcome / 결핵및호흡기질환

BACKGROUND: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. METHODS: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study. Attributes such as keratinization, tumor budding, single cell invasion, and nuclear size within the tumor, as well as immunohistochemistry of Bcl-xL and pS6 expressions, were evaluated. RESULTS: The keratinizing and nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and morphologic parameters such as nuclear diameter, tumor budding, and single cell invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%) had a history of smoking, whereas the nonkeratinizing group had a relatively higher proportion of never-smokers relative to the keratinizing group (24.0% vs. 2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may inhibit keratinization), did not correlate significantly with the presence of keratinization. Patients with the keratinizing subtype had a significantly shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test), and a multivariate analysis showed that keratinization was an independent, poor prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090–5.233; p=0.030). CONCLUSION: In lung SCC, keratinization is associated with a poor prognosis, and might be associated with smoking.

Study on the inhibitory effect of the black garlic extract on the growth of hela cells / 中国医师杂志

Objective To explore the effect of black garlic extract on HeLa cells and its possible molecular mechanisms.Methods Inhibitory rate of HeLa cells was detected with methyl thiazolyl tetrazolium(MTT).Flow cytometry annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) was used to detect tumor cell apoptosis.Flow cytometry was used to measure cell-cycle changes.Immunohistochemistry method was used to detect expressions of tumor proteins bax and Bcl-2.Results Black garlic extract significantly inhibited the growth of HeLa cells.Black garlic extract significantly induced apoptosis of HeLa cells.The apoptosis rate was (53.26 ± 1.78)％ in the black garlic high-dose group,and (3.68 ±0.11)％ in the control group.Black garlic extract affected cell cycle,upregulated bax expression,and downregulated bcl-2 expression.Conclusions Black garlic extract significantly induced the apoptosis of HeLa cells.This effect might be caused through increasing G2/M cells or changing expressions of bax and bcl-2.

Effect of pioglitazone on the expression of PPARγ, NF-κB c-Rel and Bcl-xL in cultured rat cortical neurons after the oxygen-glucose/reoxygenation / 国际脑血管病杂志

Objective To investigate the effect of pioglitazone (PIO) on the expression of peroxisome proliferators-activated receptor γ (PPARγ),nuclear factor-κB (NF-κB) c-Rel and anti-apoptosis factor Bcl-xL in cultured Wistar rat cortical neurons after oxygen-glucose deprivation/reoxygenation (OGD/R).Methods The rat cerebral cortical neurons were primarily cultured in vitro and a model of OGD/R was induced.The rats were divided into 7 groups:normal,OGD 4 h/R 6 h,OGD 4 h/R 12 h,OGD 4 h/R 6 h + PIO,OGD 4 h/R 6 h + PPARγ inhibitor T0070907 (TIO),OGD 4 h/R 12 h + PIO,and OGD 4 h/R 12 h + TIO groups.Western blot was used to detect the expression of PPARγ and NF-κB c-Rel protein in neurons.Reverse transcriptionpolymerase chain reaction assay was used to detect the expression of Bcl-xL mRNA in neurons.Results Western blot analysis showed that the expression levels of PPARγ and NF-κB c-Rel proteins after OGD/R were increased significantly compared to those of the normal group (P ＜0.01).After giving PIO,the expression levels of PPARγ and NF-κB c-Rel proteins were further increased,and they were significantly higher than those in the OGD 4 h/R 6 h and OGD 4 h/R 12 h groups (P ＜0.01),and after giving TIO,the expression levels of PPARγ and NF-κB c-Rel proteins were decreased,and they were significantly lower than those in the OGD/R group (P ＜0.05) and the corresponding PIO group (P ＜0.01).Reverse transcription-polymerase chain reaction analysis showed that the expression level of Bcl-xL mRNA in the OGD 4 h/R 6 h group was significantly higher than that in the normal group (P ＜0.01).The expression level of Bcl-xL mRNA in the PIO group was significantly higher than that in the OGD 4 h/R 6 h and OGD 4 h/R 12 h groups (P ＜0.01).After giving TIO,the expression of Bcl-xL mRNA was decreased.It was significantly lower than that in the OGD/R and corresponding PIO groups (P ＜ 0.05 and P ＜ 0.01).Conclusions PIO can upregulate the expression of PPARγ protein in cultured cortical neurons after OGD/R,and then increase the expression of anti-apoptotic factor Bcl-xL mRNA of NF-κB c-Rel regulation.This may be the part mechanism of PPARγ neuroprotective effect.

The expression and meaning of bcl-xL in superficial bladder tumor / 中国医师进修杂志

Objective To investigate the relations of the expression of bcl-xL in superficial bladder tumor and prognosis. Method The expression of bcl-xL was detected by envision system in 80 cases of superficial bladder tumor. Results In patients with high expression of bcl-xL, the recurrence rate was higher than that of normal expression [71.4%(30/42) vs 50.0%(19/38) ,P < 0.05], and the recurrence of time as early as normal expression [(16.0 ± 1.2) months vs (36.0 ± 4.5) months](P < 0.05). Conclusion The expression of bcl-xL could effectively predict the prognosis of patients with bladder tumor, those who with high expression of-bcl-xL have bad prognosis.

Calcium overload is essential for the acceleration of staurosporine-induced cell death following neuronal differentiation in PC12 cells

Differentiation of neuronal cells has been shown to accelerate stress-induced cell death, but the underlying mechanisms are not completely understood. Here, we find that early and sustained increase in cytosolic ([Ca2+]c) and mitochondrial Ca2+ levels ([Ca2+]m) is essential for the increased sensitivity to staurosporine-induced cell death following neuronal differentiation in PC12 cells. Consistently, pretreatment of differentiated PC12 cells with the intracellular Ca2+-chelator EGTA-AM diminished staurosporine-induced PARP cleavage and cell death. Furthermore, Ca2+ overload and enhanced vulnerability to staurosporine in differentiated cells were prevented by Bcl-XL overexpression. Our data reveal a new regulatory role for differentiation-dependent alteration of Ca2+ signaling in cell death in response to staurosporine.

Relationship and significance of HIF-1α and bcl-XL in gastric cancer / 肿瘤研究与临床

Objective To study the expression of HIF-1α and bcl-XL in gastric cancer and their relationship with tumor angiogenesis,clinicopathologic feature and prognosis.Methods Immunohistochemical technique was used to detect the expression of HIF-1α and bcl-XL in 54 cases of gastric canoer.SPSS 12.0 software was used to analyze the relationship between the expression of HIF-1α, bcl-XL and tumor angiogenesis,clinicopathologic feature of patients.Results The positive expression rate of HIF-1α in gastric cancer(74.07%) was significantly higher than that in normal gastric tissue(0),P＜0.01;The expression of HIF-1α in gastric cancer was significantly associated with TNM stage,invasive depth and lymph-node metastasis,P＜0.05 or P＜0.01;The positive expression rate of bcl-XL in gastric cancer(53.7%) was significantly higher than that in normal gastric tissue(33.3%),P＜0.05;The expression of bcl-XL in gastric cancer was significantly associated with histological types,TNM stage and lymph-node metastasis,P＜0.05;There was a positive correlation between expression of HIF-1α and bcl-XL (r=0.41,P＜0.05).Conclusion HIF-1α and bcl-XL play a very important role in the development in gastric cancer and could be a factor in diagnosis of gastric cancer and estimation of prognosis.

Inhibition of gamma ray-induced apoptosis by stimulatory heterotrimeric GTP binding protein involves Bcl-xL down-regulation in SH-SY5Y human neuroblastoma cells

Heterotrimeric GTP-binding proteins (G proteins) transduce extracellular signals into intracellular signals by activating effector molecules including adenylate cyclases that catalyze cAMP formation, and thus regulate various cellular responses such as metabolism, proliferation, and apoptosis. cAMP signaling pathways have been reported to protect cells from ionizing radiation-induced apoptosis, but however, the protective mechanism is not clear. Therefore, this study aimed to investigate the signaling molecules and the mechanism mediating the anti-apoptotic action of cAMP signaling system in radiation-induced apoptosis. Stable expression of a constitutively active mutant of G alpha s (G alpha sQL) protected gamma ray-induced apoptosis which was assessed by analysis of the cleavages of PARP, caspase-9, and caspase-3 and cytochrome C release in SH-SY5Y human neuroblastoma cells. G alpha sQL repressed the gamma ray-induced down-regulation of Bcl-xL protein, but transfection of Bcl-xL siRNA increased the gamma ray-induced apoptosis and abolished the anti-apoptotic effect of G alpha sQL. G alpha sQL decreased the degradation rate of Bcl-xL protein, and it also restrained the decrease in Bcl-xL mRNA by increasing the stability following ionizing irradiation. Furthermore, prostaglandin E2 that activates G alpha s was found to protect gamma ray-induced apoptosis, and the protective effect was abolished by treatment with prostanoid receptor antagonist specific to EP2/4R subtype. Moreover, specific agonists for adenosine A1 receptor that inhibits cAMP signaling pathway augmented gamma ray-induced apoptosis. From this study, it is concluded that Galphas-cAMP signaling system can protect SH-SY5Y cells from gamma ray-induced apoptosis partly by restraining down-regulation of Bcl-xL expression, suggesting that radiation-induced apoptosis can be modulated by GPCR ligands to improve the efficiency of radiation therapy.