Article

The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins.

Department of Pathology, University of California, San Francisco, 94143, USA.
Current Molecular Medicine (Impact Factor: 3.61). 03/2006; 6(1):99-109. DOI: 10.2174/156652406775574587
Source: PubMed

ABSTRACT Irreversible perturbations in the homeostasis of the endoplasmic reticulum (ER) are thought to lead to apoptosis and cell loss in a number of important human diseases, including Alzheimer disease, Parkinson disease, and type 2 diabetes. However, the exact mechanisms that lead from ER stress to cell death remain incompletely understood. Recent work has shown that the BCL-2 family of proteins plays a central role in regulating this form of cell death, both locally at the ER and from a distance at the mitochondrial membrane.

0 Bookmarks
 · 
51 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson’s disease (PD) is a common chronic neurodegenerative disorder primarily caused by death of dopaminergic neurons in the substantia nigra pars compacta (SN). Human neuroblastoma SH-SY5Y cells have been broadly utilized in studies of mechanisms of the pathogenesis underlying MPP+-induced PD mimics. However, the pathways impacted in MPP+-treated SH-SY5Y cells have not been examined at genome-wide level. Here, we examined genome-wide response of MPP+-treated SH-SY5Y cells with whole genome expression array including 47,231 probes and identified 169 genes that were significantly differentially expressed in a significance analysis of micro-arrays. Gene ontology (GO) terms such as GO:0051900 (regulation of mitochondrial depolarization), GO:0008637 (apoptotic mitochondrial changes), GO:0090090 (negative regulation of canonical Wnt receptor signaling pathway), and GO:0009968 (negative regulation of signal transduction) were significantly overrepresented in a differentially expressed genes (DEGs) analysis. The DEG information and their fold changes in expression were used to identify the pathways impacted. Five pathways, including systemic lupus erythematosus, alcoholism, prion diseases, the Wnt signaling pathway, and axon guidance had a significant impact at a threshold of P G = 0.05. Our results suggest that MPP+ toxicity of SH-SY5Y cells might be related to transcriptional dysregulation by a nucleosome structural defect, endoplasmic reticulum stress, and inhibited canonical Wnt signaling.
    Biotechnology and Bioprocess Engineering 03/2014; 19(2):332-340. · 1.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fanconi Anemia (FA) is a rare and complex inherited blood disorder associated with bone marrow failure and malignancies. Many alterations in FA physiology appear linked to red-ox unbalance including alterations in the morphology and structure of nuclei, intermediate filaments and mitochondria, defective respiration, reduced ATP production and altered ATP/AMP ratio. These defects are consistently associated with impaired oxygen metabolism indeed treatment with antioxidants N-acetylcysteine (NAC) and resveratrol (RV) does rescue FA physiology. Due to the importance of the intracellular calcium signaling and its key function in the control of intracellular functions we were interested to study calcium homeostasis in FA. We found that FANCA cells display a dramatically low intracellular calcium concentration ([Ca(2+)]i) in resting conditions. This condition affects cellular responses to stress. The flux of Ca(2+) mobilized by H2O2 from internal stores is significantly lower in FANCA cells in comparison to controls. The low basal [Ca(2+)]i in FANCA appears to be an actively maintained process controlled by a finely tuned interplay between different intracellular Ca(2+) stores. The defects associated with the altered Ca(2+) homeostasis appear consistently overlapping those related to the unbalanced oxidative metabolism in FA cells underlining a contiguity between oxidative stress and calcium homeostasis.
    Scientific reports. 01/2015; 5:8088.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thin epitaxial films of CoSi2 have been grown on strained heterostructures with Ge contents between 20 and 25 at% by molecular beam epitaxy (MBE). Single-oriented CoSi2(001) films of high crystalline quality (xmin = 4.6%) and smooth surface morphology with low resistivities (17 μΩ · cm) could be obtained using a special template method and an additional thin silicon sacrificial cap layer on top of the heterostructure. The films were characterized using RHEED, LEED, in-situ AES, SIMS, RBS, SEM, TEM and sheet resistance measurements. The results are compared with films grown on mere Si(001) substrates and on heterostructures grown without the use of a silicon cap layer. It is demonstrated that a silicon sacrificial cap layer is essential for the growth of high-quality single-domain CoSi2(001) films on heterostructures.
    Journal of Crystal Growth 07/1996; 165(1). · 1.69 Impact Factor