Apoptosis
Apoptosis is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast.[1] Biochemical events lead to characteristic cell changes (morphology) and death.[2] These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. That is around 0.5% of the 13 trillion cells of an average human adult. For an average human child between eight and fourteen years old, each day the approximate lost is 20 to 30 billion cells.[3]
In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytes are able to engulf and remove before the contents of the cell can spill out onto surrounding cells and cause damage to them.[4]
Because apoptosis cannot stop once it has begun, it is a highly regulated process. Apoptosis can be initiated through one of two pathways. In the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. Weak external signals may also activate the intrinsic pathway of apoptosis.[5] Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate executioner caspases, which then kill the cell by degrading proteins indiscriminately.
In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer. Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis.[6]
See also
- Senecent Cells
- Wikipedia - Apoptosis
References
- ↑ Green D; "Means to an End: Apoptosis and other Cell Death Mechanisms" , ISBN: 978-0-87969-888-1
- ↑ Böhm I & Schild H: Apoptosis: the complex scenario for a silent cell death. Mol Imaging Biol 2003. (PMID 14499155) [PubMed] [DOI] In multicellular organisms, homeostasis is maintained by a balance between cell proliferation and apoptosis (programmed cell death). It is a physiological form of cell death responsible for the deletion of not reparable damaged, mutated, or cells which have lost their function. Apoptosis can be distinguished by morphological and biochemical characteristics from necrosis (pathological cell death). Apoptotic cell death does not disturb surrounding cells. To achieve the elimination of cells without an inflammatory reaction, a complex interplay of several molecules is necessary. Apoptosis either starts from the cell surface (CD95-CD95L), the mitochondrion or from the nucleus. The cell biological events run in a cascaded fashion and are regulated by either enhancer or anti-apoptotic signals that probably may stop the executions machinery. The knowledge about apoptosis helps to understand pathophysiologic conditions, to better diagnose and treat them by molecular radiological techniques.
- ↑ Karam JA; "Apoptosis in Carcinogenesis and Chemotherapy" , ISBN: 978-1-4020-9597-9
- ↑ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P; "Molecular Biology of the Cell (textbook)" , pp. 1115 , ISBN: 978-0-8153-4105-5
- ↑ Raychaudhuri S: A minimal model of signaling network elucidates cell-to-cell stochastic variability in apoptosis. PLoS One 2010. (PMID 20711445) [PubMed] [DOI] [Full text] BACKGROUND: Signaling networks are designed to sense an environmental stimulus and adapt to it. We propose and study a minimal model of signaling network that can sense and respond to external stimuli of varying strength in an adaptive manner. The structure of this minimal network is derived based on some simple assumptions on its differential response to external stimuli. METHODOLOGY: We employ stochastic differential equations and probability distributions obtained from stochastic simulations to characterize differential signaling response in our minimal network model. Gillespie's stochastic simulation algorithm (SSA) is used in this study. CONCLUSIONS/SIGNIFICANCE: We show that the proposed minimal signaling network displays two distinct types of response as the strength of the stimulus is decreased. The signaling network has a deterministic part that undergoes rapid activation by a strong stimulus in which case cell-to-cell fluctuations can be ignored. As the strength of the stimulus decreases, the stochastic part of the network begins dominating the signaling response where slow activation is observed with characteristic large cell-to-cell stochastic variability. Interestingly, this proposed stochastic signaling network can capture some of the essential signaling behaviors of a complex apoptotic cell death signaling network that has been studied through experiments and large-scale computer simulations. Thus we claim that the proposed signaling network is an appropriate minimal model of apoptosis signaling. Elucidating the fundamental design principles of complex cellular signaling pathways such as apoptosis signaling remains a challenging task. We demonstrate how our proposed minimal model can help elucidate the effect of a specific apoptotic inhibitor Bcl-2 on apoptotic signaling in a cell-type independent manner. We also discuss the implications of our study in elucidating the adaptive strategy of cell death signaling pathways.
- ↑ Elmore S: Apoptosis: a review of programmed cell death. Toxicol Pathol 2007. (PMID 17562483) [PubMed] [DOI] [Full text] The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.