Article

Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis.

Department of Medicine and Pharmacology, Comprehensive Cancer Center and University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA.
Annual Review of Physiology (Impact Factor: 14.7). 02/2008; 70:73-91. DOI: 10.1146/annurev.physiol.70.021507.105852
Source: PubMed

ABSTRACT Bcl-2 family members are important regulators of cell survival and cell death. Researchers have focused mainly on mitochondria, where both proapoptotic and antiapoptotic family members function to regulate the release of cytochrome c and other mediators of apoptosis. However, as reviewed here, Bcl-2 family members also operate on another front, the endoplasmic reticulum (ER), to both positively and negatively regulate the release of Ca2+. There is abundant evidence that Ca2+ signals trigger apoptosis in response to a wide variety of agents and conditions. Conversely, Ca2+ signals can also mediate cell survival. Recent findings indicate that Bcl-2 interacts with inositol 1,4,5-trisphosphate (IP3) receptor Ca2+ channels on the ER, regulating their opening in response to IP3- and thus inhibiting IP3-mediated Ca2+ signals that induce apoptosis while enhancing Ca2+ signals that support cell survival.

0 Bookmarks
 · 
129 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. DOI:10.1007/s12257-013-0754-x · 1.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aluminium (Al), a ubiquitous element in nature is associated with the onset of Alzheimer's disease. On the other hand, zinc (Zn) is an essential trace element that regulates large number of physiological processes in the human body. The present study was conducted to explore the role of zinc, if any, in regulating apoptotic machinery during Al induced neurodegeneration in rat. Male sprague dawley rats weighing 140-160 g were divided into four different groups viz: Normal control, Al treated (100 mg/kg b.wt./day), Zn treated (227 mg/l) and combined Al and Zn treated. All the treatments were carried out for a total duration of 8 weeks. Al treatment resulted in a significant increase in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6, caspase 7 but decreased the Bcl-2 in both the cerebrum and cerebellum. However, Zn supplementation to Al treated rats resulted in a reduction in the protein expressions of cytochrome c, Bax, Apaf-1, caspase 9, caspase 3 (p17), caspase 8, caspase 6 and caspase 7 whereas it elevated the Bcl-2 in both the regions. Further, gene expressions of caspase 3 and caspase 9 were also found to be elevated after Al treatment, which however were reduced following Zn co-treatment. The electron-microscopic analysis of brain revealed that Al intoxication resulted in a number of degenerative signs at ultrastructural level, which were appreciably improved upon Zn supplementation. The present study suggests that Zn provides protection against Al induced neurotoxicity by triggering anti-apoptotic machinery.
    BioMetals 11/2014; 28(1). DOI:10.1007/s10534-014-9803-y · 2.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Seeds of nine genotypes of coriander were ground in cryogenic grinder and traditional grinding mill. Effect of cryogenic grinding on volatile oil and its constituents has been analyzed. All the genotypes showed difference in essential oil content whether ground cryo or non cryogenically. Volatile oil content was significantly high in cryo ground samples ranged from 0.14 % in genotypes RCr 436 to 0.39 % in genotype Sindhu. Ten major compounds were identified by Gas chromatography, percentage of which in cryo ground seeds of different genotypes was ranging from 99.65 to 99.99 % while in non cryo ground seeds it was ranging from 91.35 to 99.98 %. Linalool was found as main constituent in all the samples, the content of which in cryo ground seeds varied from 81.42 % in genotype Australia to 93.78 % in genotype Sadhna. Non cryo ground seeds of all genotypes showed less linalool content ranging from 73.49 % in genotype Swati to 87.69 % in genotype RCr 436. alpha-Pinene and geranyl acetate were another constituent showed large variation in cryo and non cryo ground seeds. Genotypes from North Indian origin like ACr 1, RCr 41, Rcr 435 and RCr 436 showed less variation in geranyl acetate content of cryo and non cryo ground samples as compare to the genotypes, Sindhu, Sadhna and Swati of South Indian origin. Two grinding techniques had significant effects on dependent variables, viz., volatile oil, its constituents like linalool, alpha-Pinene and geranyl acetate. It is found that cryogenic grinding technique was superior to ambient grinding in terms of monoterpenes retention in the ground powder and was distinctly high in top notes which represented freshness while marginally high in basic notes also.
    Journal of essential oil-bearing plants JEOP 08/2014; 17(3):385-392. DOI:10.1080/0972060X.2014.895197 · 0.19 Impact Factor