Expression Of Apoptosis Regulator Bcl-2 Research Articles

Smooth muscle-specific deletion of MnSOD exacerbates diabetes-induced bladder dysfunction in mice.

Bladder dysfunction in diabetes progresses gradually over time. However, the mechanisms of the development are not clear. We tested the hypothesis that oxidative stress plays a key role in the development of diabetic bladder dysfunction using an inducible smooth muscle (SM)-specific superoxide dismutase 2 (Sod2) gene knockout (SM-Sod2 KO) mouse model. Eight-week-old male Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice and wild-type mice were assigned to diabetic or control groups. 4-Hydroxytamoxifen was injected into Sod2lox/lox, SM-CreERT2(ki)Cre/+ mice to activate CreERT2-mediated deletion of Sod2. Diabetes was induced by injection of streptozotocin, whereas control mice were injected with vehicle. Nine weeks later, bladder function was evaluated, and bladders were harvested for immunoblot analysis. Wild-type diabetic mice presented compensated bladder function along with increased nitrotyrosine and MnSOD in detrusor muscle. Induction of diabetes in SM-Sod2 KO mice caused deteriorated bladder function and even greater increases in nitrotyrosine compared with wild-type diabetic mice. Expression levels of apoptosis regulator Bax and cleaved caspase-3 were increased, but apoptosis regulator Bcl-2 expression was decreased in detrusor muscle of both diabetic groups, with more pronounced effects in SM-Sod2 KO diabetic mice. Our findings demonstrate that exaggerated oxidative stress can accelerate the development of bladder dysfunction in diabetic mice and the enhanced activation of apoptotic pathways in the bladder may be involved in the process.

P229 - Increased expression of apoptosis regulator bcl-2 is an independent prognostic factor for worse overall survival in triple-negative breast cancer patients

P229 - Increased expression of apoptosis regulator bcl-2 is an independent prognostic factor for worse overall survival in triple-negative breast cancer patients

Triptolide suppresses the proliferation and induces the apoptosis of nasopharyngeal carcinoma cells via the PI3K/Akt pathway.

Nasopharyngeal carcinoma (NPC) is an endothelium-associated malignancy that is heavily influenced by Epstein Barr virus infection. Triptolide, extracted from Tripterygium wilfordii, has been proven to possess anti-inflammatory, immunosuppressive and anti-cancerous activity. Although the effect of triptolide on numerous cancer cell types has been outlined, its effect in NPC remained unclear. The present study investigated the effects and underlying mechanisms of triptolide in C666-1 and NP69 cells. It was revealed that triptolide significantly inhibited proliferation and induced apoptosis in C666-1 cells. Increased levels of cleaved-caspase-3 and apoptosis regulator BAX, decreased expression of apoptosis regulator Bcl-2, and reduced phosphorylation of RAC-α serine/threonine-protein kinase (Akt), were responsible for this induction of apoptosis. Notably, pretreating C666-1 cells with the phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor LY294002 suggested that with increasing concentrations of LY294002, triptolide exhibited decreasing ability to suppress proliferation and induce apoptosis in these cells. In conclusion, the results demonstrated that triptolide suppressed the proliferation and induced the apoptosis of C666-1 cells in a PI3K/Akt-dependent manner and therefore, may serve as a promising therapeutic candidate for NPC.

Inhibition of maternally expressed gene 3 attenuated lipopolysaccharide-induced apoptosis through sponging miR-21 in renal tubular epithelial cells.

Acute kidney injury (AKI)results inretention of waste products anddysregulation of extracellular volume and electrolytes, thus leading to a variety of complications. Recent advances in long noncoding RNAs suggested their close relationship with disease progression. In the current study, we investigated the role and mechanism of maternally expressed gene 3 (MEG3) on AKI pathogenesis. Real-time polymerase chain reaction found that the expression of MEG3 was significantly increased in both kidney tissues and TKPTS cells induced by lipopolysaccharide (LPS). Western blot assay showed that the expression of apoptosis regulator Bcl-2 was increased in MEG3-inhibited TKPTS cells. Flow cytometry assay confirmed that LPS-induced apoptosis was significantly attenuated after transfection of si-MEG3. The RNAhybrid informatics algorithm predicted that there was a strong binding capacity between miR-21 and MEG3. Luciferase reporter assay confirmed that MEG3 could function as a competing endogenous RNA of miR-21. The antiapoptotic effect of si-MEG3 could be neutralized by a miR-21 inhibitor, demonstrated by the decreased expression of Bcl-2 and flow cytometry results. Further investigation showed that programmed cell death protein 4 (PDCD4), a validated target of miR-21, was highly expressed in both injured kidney tissues and LPS-stimulated TKPTS cells. Meanwhile, the protein expression of PDCD4 was significantly reduced by inhibition of MEG3, but retrieved by coinhibition of MEG3 and miR-21. In conclusion, our results demonstrated that inhibition of MEG3 could attenuate LPS-induced apoptosis in TKPTS cells by regulating the miR-21/PDCD4 pathway, suggesting that the MEG3/miR-21/PDCD4 axis could be developed as a potential therapeutic target of AKI.

Sulforaphane sensitizes human breast cancer cells to paclitaxel-induced apoptosis by downregulating the NF-κB signaling pathway.

Sulforaphane (SFN), an isothiocyanate present in cruciferous vegetables, has been demonstrated to inhibit the growth of various types of cancer cell. The aim of the present study was to investigate whether SFN sensitizes breast cancer cells to paclitaxel-induced apoptosis and to identify the signal pathway through which SFN mediates apoptosis. Combined treatment of breast cancer cells with SFN and paclitaxel resulted in increased activation of apoptotic signaling pathway members, including caspase-3, -8 and -9, and cytochrome c, compared with treatment with SFN or paclitaxel alone. In addition, treatment with SFN and paclitaxel resulted in downregulation of the nuclear factor kappa B signaling pathway, and reduced protein expression of apoptosis regulator Bcl-2 and phosphorylated AKT serine/threonine kinase. Furthermore, SFN-paclitaxel-induced apoptosis was inhibited by overexpression of Bcl-2. The results of the present study suggest that combined treatment with SFN and paclitaxel is a novel therapeutic strategy for the treatment of breast cancer.

Роль імуногістохімічного дослідження у діагностиці цервікальної інтраепітеліальної неоплазії різного ступеня тяжкості

The objective: the finding of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia of different severity to optimize the diagnosis and prognosis of the disease. Patients and methods. The study involved 42 women of reproductive age with cervical intraepithelial the neoplasia of the cervix varying degrees applied to the doctor of cervical pathology Zhitomir regional oncologic dispensary. All women (n=42) were divided into groups. The first group included 15 patients (35.7%) with cervical intraepithelial neoplasia with mild. The second group included 13 women (31%) with cervical intraepithelial neoplasia a moderate degree. The third group was represented by patients with cervical intraepithelial neoplasia with severe – 14 respondents (33.3 per cent). Results. Marker BCL-2 in patients of the first group was positive in 7 patients (46.7%), Smooth Muscule Actin was positive in 9 patients (60%) and Ki-67 was diagnosed in 8 of the surveyed women (53.3%). In the second group of BCL-2 was positive in 8 patients (61.5%), Clone 124, Smooth Muscule Actin, Clone 1A4 was positive in 9 patients (69.2%), and Ki-67 was diagnosed in 12 of the surveyed women (92.3%). Marker BCL-2 in patients of the third group was positive in 12 patients (85.7%), Smooth Muscule Actin was positive in 10 patients (71.4%) and Ki-67 was diagnosed in 13 of the surveyed women (92.9% ). Conclusion. Carcinogenesis is associated with molecular genetic damage to the cervix. Some of the products of this process can be used as prognostic and diagnostic markers of tumor progression. Determination of protein expression of apoptosis regulator BCL-2, Smooth Muscule Actin and the antigen Ki-67 in cervical intraepithelial neoplasia makes it possible to accurately verify the diagnosis and to predict the course of pathological changes in the flat epithelium of the cervix. Key words: cervical intraepithelial neoplasia, cervical cancer, morphological diagnostics of precancerous lesions, BCL-2, Smooth Muscule Actin, Ki-67.

Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia

Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.