BimL displacing Bcl-xL promotes Bax translocation during TNFα-induced apoptosis

Zhang, Lan; Xing, Da; Chen, Miaojuan

doi:10.1007/s10495-008-0226-5

Cited by 36 publications

(30 citation statements)

References 41 publications

(53 reference statements)

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“…Our work demonstrates that the NF-B family of proteins is necessary for MN survival; knockdown of these proteins probably deregulates gene expression of proteins that exert their function upstream of the mitochondria. It has been recently demonstrated that the BH3-only protein, Bim, displaces Bcl-x L in the mitochondria and promotes Bax translocation during TNF␣-induced apoptosis in PC12 cells (Zhang et al, 2008). In our model, we observed in shRelA-treated cultures an increase of Bim protein level, suggesting that this protein could be regulating the apoptotic cell death process caused by the blockade of NF-B signaling.…”

Section: Discussionmentioning

confidence: 48%

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The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

Mincheva¹,

Garcerá²,

Gou-Fàbregas³

et al. 2011

J. Neurosci.

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In vivo and in vitro motoneuron survival depends on the support of neurotrophic factors. These factors activate signaling pathways related to cell survival or inactivate proteins involved in neuronal death. In the present work, we analyzed the involvement of the nuclear factor-B (NF-B) pathway in mediating mouse spinal cord motoneuron survival promoted by neurotrophic factors. This pathway comprises ubiquitously expressed transcription factors that could be activated by two different routes: the canonical pathway, associated with IKK␣/IKK␤ kinase phosphorylation and nuclear translocation RelA (p65)/p50 transcription factors; and the noncanonical pathway, related to IKK␣ kinase homodimer phosphorylation and RelB/p52 transcription factor activation. In our system, we show that neurotrophic factors treatment induced IKK␣ and IKK␤ phosphorylation and RelA nuclear translocation, suggesting NF-B pathway activation. Protein levels of different members of the canonical or noncanonical pathways were reduced in a primary culture of isolated embryonic motoneurons using an interference RNA approach. Even in the presence of neurotrophic factors, selective reduction of IKK␣, IKK␤, or RelA proteins induced cell death. In contrast, RelB protein reduction did not have a negative effect on motoneuron survival. Together these results demonstrated that the canonical NF-B pathway mediates motoneuron survival induced by neurotrophic factors, and the noncanonical pathway is not related to this survival effect. Canonical NF-B blockade induced an increase of Bim protein level and apoptotic cell death. Bcl-x L overexpression or Bax reduction counteracted this apoptotic effect. Finally, RelA knockdown causes changes of CREB and Smn protein levels.

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Section: Discussionmentioning

confidence: 48%

“…Moreover, Bim displaces Bcl-x L in the mitochondria and promotes Bax translocation during TNF␣-induced apoptosis (Zhang et al, 2008). In this context, we decided to analyze whether Bim protein levels changed when the canonical NF-B pathway was knocked down.…”

Section: Effect Of Nf-b Pathway Inhibition On Bim Protein Levelmentioning

confidence: 99%

The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

Mincheva¹,

Garcerá²,

Gou-Fàbregas³

et al. 2011

J. Neurosci.

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“…Bcl-2 directly interacts with the proapoptotic molecules in the mitochondrion to antagonize apoptosis. 34,35) The interaction between the Bcl-2 protein and the proapoptotic proteins may determine the fate of a cell. Thus, we first detected the expression of Bcl-2 in the kidney of STZ and non-STZ treated rats with or without minocycline-treatment.…”

Section: Discussionmentioning

confidence: 99%

Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy

Yuan

Zhang

Zheng

et al. 2016

Biological & Pharmaceutical Bulletin

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The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/ kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis. Key words minocycline; kidney injury; rat model; diabetic nephropathy (DN)Diabetes mellitus is a complex disease that causes altered glucose homeostasis, 1) and diabetic nephropathy (DN) is the major microvascular complication of diabetes which is prevalent among diabetic patients.2) It is estimated that DN progresses to end-stage renal disease in up to 30% of patients with diabetes. DN is currently the leading cause of end-stage renal disease in most developed societies and is increasingly prevalent in developing countries. The clinical characteristics of DN are progressive urinary albumin excretion and gradual decline of renal function, which results from the multiple pathophysiologic dysfunctions of diabetes. The appearance of microalbuminuria is regarded as the hallmark of DN onset at its early stage, and the continuous existence of albuminuria plays a crucial role in the damage of both renal structure and function. Although the treatment and understanding of DN are progressing, in clinical practice, the strict control of glucose and blood pressure, and the blockade of the renin-angiotensin system can only slow the progression of DN, however, no available therapy can cure DN.The increased urinary albumin excretion is due to the dysfunction of the glomerular barrier, which is considered to be a key target for the prevention and treatment of DN. Among the elementary ingredients of glomeruli structure, the podocyte and its foot process play the pivotal role in maintenance of permselective function of the glomerular barrier. 3)Minocycline is a semi-synthetic derivative of...

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“…In the activation of caspase cascade, of three main pathways including DR-ligand complex-activated caspase-8 pathway, the mitochondria dependent pathway characterized by mitochondrial membrane permeability change according to pro-apototic Bax/anti-apoptotic Bcl-2 ratio, consecutive cytochrome c release and subsequent activation of apoptosome-associated caspases-9 and -3 and the endoplasmic reticulum(ER)-specific apoptotic pathway involving caspase-12 activation, former two pathways are more noteworthy regarding both apoptotic pathways in various cancer cells and considered a potential target of developing new anticancer drugs [51][52][53] where induction of apoptosis critically depends on upregulation of proapoptotic caspases known as executioners of apoptosis [54][55][56] . In the expression of apoptosis related proteins, SVT with TRAIL in HT29 cells represented increased Bax/Bcl-2 ratio, subsequently upregulated intrinsic apoptotic pathway related cleaved caspase-9, -3 as well as activated extrinsic DR-mediated apoptotic pathway related caspase-8, suggesting SVT exerts substantial influence upon bilateral apoptosis in them nevertheless of TRAIL resistance (Fig.…”

Section: ⅳ Discussionmentioning

confidence: 99%

Effect of Snake Venom Toxin on Inhibition of Colorectal Cancer HT29 Cells Growth via Death Receptors Mediated Apoptosis

Shim¹,

Song²

2014

The Acupuncture

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[Abstract]Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in HT29 human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

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BimL displacing Bcl-xL promotes Bax translocation during TNFα-induced apoptosis

Cited by 36 publications

References 41 publications

The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons

Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy

Effect of Snake Venom Toxin on Inhibition of Colorectal Cancer HT29 Cells Growth via Death Receptors Mediated Apoptosis

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