Programmed Cell Death in Animal Development and Disease

Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell (Impact Factor: 32.24). 11/2011; 147(4):742-58. DOI: 10.1016/j.cell.2011.10.033
Source: PubMed


Programmed cell death (PCD) plays a fundamental role in animal development and tissue homeostasis. Abnormal regulation of this process is associated with a wide variety of human diseases, including immunological and developmental disorders, neurodegeneration, and cancer. Here, we provide a brief historical overview of the field and reflect on the regulation, roles, and modes of PCD during animal development. We also discuss the function and regulation of apoptotic proteins, including caspases, the key executioners of apoptosis, and review the nonlethal functions of these proteins in diverse developmental processes, such as cell differentiation and tissue remodeling. Finally, we explore a growing body of work about the connections between apoptosis, stem cells, and cancer, focusing on how apoptotic cells release a variety of signals to communicate with their cellular environment, including factors that promote cell division, tissue regeneration, and wound healing.

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Available from: Yaron Fuchs, Jun 29, 2014
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    • "Recently, an intensive research focuses on the image analysis for various medical and biological applications and the HWC 2015 development of the automated microscopic cells detection, segmentation, counting and classification as in [5] [6] [7] [8] [9] [10] [11] [12] [13]. Various imaging approaches have been developed to study and investigate the apoptosis in individual cells. "
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    ABSTRACT: In the past few years, research on cell death has developed significantly, owing to its importance for various diseases’ severity determination and diagnosis. Different varieties of cell death are often identified by morphological criteria, exclusive of a clear reference to specific biochemical mechanisms. Therefore, it is significant to determine accurately the “percentage apoptosis”. This work proposed an algorithm that created in ImageJ v. 1.49v commands and macro language functions to classify both dead cells and dying cells. A stained images using Caspase stain of albino rats hippocampus specimens using light microscope are used to evaluate the system performance. The algorithm analyzes color of the obtained objects on the enhanced image after using the median filter and the logarithmic transformation. The main descriptors used for feature extraction are the area, shape, light nucleus, and the brown regions intensity. A threshold value is to be used to distinguish between the dead cells that characterized by dark brown color, while the dying cells have less brown intensity. This study proposed a novel system to perform the classification based on color intensity and contrast changes. After feature extraction stage, the Back propagation neural network (BPNN) classifier was used. The experimental results proved that the proposed automated system achieves 82.92% mean accuracy, where the dying cells and dead cells classification accuracy have the values of 76.76%, and 89.08%; respectively, thus the mean accuracy of the proposed system has the value of 82.92%.
    Healthy World Conference 2015 - A Healthy World for a Happy Life, Kakinada (AP) India [JNTU]; 09/2015
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    • "2007 ; Moon et al . 2008 ; Fuchs and Steller 2011 ; Denton et al . 2013 ) , are omnipresent . "
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    ABSTRACT: Earlier we showed formulation-specific beneficial effects of dietary supplement of Ayurvedic Amalaki Rasayana (AR, a herbal formulation) and Rasa-Sindoor (RS, a mercury-based organo-metallic formulation) on various biological parameters in Drosophila, parallel to traditional Ayurvedic literature. These formulations also suppressed cell death and pathology in fly models of neurodegeneration. To understand basis of inhibition of apoptosis, we examined effects of AR and RS on induced and developmental apoptosis in Drosophila. Dietary AR or RS significantly reduced apoptosis induced by GMR-GAL4-, sev-GAL4-or hs-GAL4-directed expression of Rpr, Hid or Grim (RHG) pro-apoptotic proteins or by GMR-GAL4-directed DIAP1-RNAi, resulting in significant restoration of organism's viability and eye morphology. AR or RS supplement enhanced levels of inhibitor of apoptosis proteins, DIAP1 and DIAP2, and of Bancal/Hrb57A, while the levels of RHG proteins and of initiator Dronc and effecter Drice caspases were reduced in non-apoptotic wild type as well as in RHG over-expressing tissues. Levels of Dronc or Drice remained unaffected in cells developmentally destined to die so that developmental apoptosis occurred normally. Elevated levels of DIAPs and reduced levels of RHG proteins and caspases reflect a more robust physiological state of AR or RS fed organisms allowing them to tolerate greater insults without triggering the cell-death response. Such homeo-static effects of these Rasayanas seem to contribute to 'healthy ageing', one of their effects suggested in traditional Ayurvedic practices. [Dwivedi V, Tiwary S and Lakhotia SC 2015 Suppression of induced but not developmental apoptosis in Drosophila by Ayurvedic Amalaki Rasayana and Rasa-Sindoor.
    Journal of Biosciences 06/2015; 40(2):1-17. DOI:10.1007/s12038-015-9521-9 · 2.06 Impact Factor
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    • "Apoptosis, also known as programmed cell death, plays a central role in the development and tissue homeostasis of all metazoans (Horvitz 2003; Danial and Korsmeyer 2004; Fuchs and Steller 2011). Apoptosis is executed by a cascade of caspase activation (Yan and Shi 2005). "
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    ABSTRACT: Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome. © 2015 Pang et al.; Published by Cold Spring Harbor Laboratory Press.
    Genes & Development 02/2015; 29(3):277-87. DOI:10.1101/gad.255877.114 · 10.80 Impact Factor
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