Glial-cell-line-derived neurotrophic factor (GDNF) has been shown to protect dopaminergic (DA) neurons against 6-hydroxydopamine (6-OHDA) toxicity. The mechanism underlying the antiapoptosis role of GDNF still needs further studies. We previously observed that nuclear factor-kappaB (NF-κB) signaling pathway, i.e. p65/p52, mediated the antiapoptosis role of GDNF in MN9D cells. Here, the DA cell line MN9D was used to explore the mechanisms underlying NF-κB p65/p52-mediated protection role of GDNF in DA neurons. The results showed that GDNF pretreatment blocked the apoptotic effects induced by 6-OHDA, with the upregulation of the antiapoptotic protein, Bcl-2 and Bcl-w, as well as the downregulation of the proapoptotic proteins, Bax and Bad. Furthermore, when sip100 plasmids were transfected into MN9D cells to inhibit the expression of p100, which was the precursor of p52, the effects of GDNF on upregulating Bcl-2 and Bcl-w were attenuated. These results indicated that GDNF could protect MN9D cells from apoptosis induced by 6-OHDA via upregulating Bcl-2 and Bcl-w expressions and downregulating Bax and Bad expressions. Moreover, NF-κB p65/p52 signaling mediated the effects of GDNF on Bcl-2 and Bcl-w expressions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3109/00207454.2013.795149 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Senolysis by ABT-263 is associated with inherent apoptotic dependence of cancer cells derived from the non-senescent state.
Cell Death Differ
December 2024
Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, CX, The Netherlands.
Cellular senescence is a stress response that cells can employ to resist cell death. Senescent cells rely on anti-apoptotic signaling for their survival, which can be targeted by senolytic agents, like the BCL-XL, BCL-2, BCL-W inhibitor ABT-263. However, the response to ABT-263 of senescent cancer cells ranges from highly sensitive to refractory.
View Article and Find Full Text PDFHRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.
Cell Death Differ
December 2024
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Senescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction.
View Article and Find Full Text PDFComprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics.
Oral Oncol
December 2024
Department of Pathology, Montefiore Medical Center / Albert Einstein College of Medicine, Bronx, NY, USA; Department of Otorhinolaryngology - Head and Neck Surgery, Montefiore Medical Center / Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:
Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC's highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood.
View Article and Find Full Text PDFNovel Tricyclo[4.2.1]Nonane and Bicyclo[2.2.1]Heptane Derivatives: Synthesis, in Vitro Biological Activities and in Silico Studies.
Chem Biodivers
October 2024
Kırıkkale University, Department of Medical Laboratory, 71450, Kırıkkale, Türkiye.
The target benzothiazole derivatives (8a-g) were synthesized starting from norbornene. The addition of dichloroketene to norbornene followed by the reduction of chlorine atoms were synthesized tricyclo[4.2.
View Article and Find Full Text PDFDissecting the neuroprotective interaction between the BH4 domain of BCL-w and the IP3 receptor.
Cell Chem Biol
October 2024
Departments of Cancer Biology and Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address:
BCL-w is a BCL-2 family protein that promotes cell survival in tissue- and disease-specific contexts. The canonical anti-apoptotic functionality of BCL-w is mediated by a surface groove that traps the BCL-2 homology 3 (BH3) α-helices of pro-apoptotic members, blocking cell death. A distinct N-terminal portion of BCL-w, termed the BCL-2 homology 4 (BH4) domain, selectively protects axons from paclitaxel-induced degeneration by modulating IP3 receptors, a noncanonical BCL-2 family target.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!