Apoptosis: Pathophysiology of Programmed Cell Death

Journal of Biology, Pharmacy and Allied Sciences, 2023

Apoptosis, programmed cell death, is an energy-dependent biochemical process which alters the cellular morphology that leads to death of cell. Apoptosis plays a major role in various cellular processes like proper functioning and development of the immune system, normal cellular turnover, hormone-induced atrophy, embryonic stage of development and chemicaltriggered cell death. Disproportionate apoptosis either more or less is a major factor for illness in many human beings including autoimmune diseases, neurodegenerative disorders, ischemic damage, and different types of cancer. The potential to stabilize the life or death of a cell is an index for its intense therapeutic property. Therefore, various signaling pathways and cell cycle machinery are the research area to focus on the control of cell cycle arrest and apoptosis. The research in the field of apoptosis moving forward at very rapid rate. Presently many key proteins are identified which are responsible for apoptosis but the mechanisms of action of these proteins are still to be elucidated. The aim of this review is to provide current knowledge in the field of apoptosis which includes the role of apoptosis in relation to health and various disease states, detection methods, and a potential alternative forms of apoptosis.

2020

Apoptosis process occurs when a cell decides to die by itself. This often happens for the better development and morphological changes of the whole organism, mostly to prevent cell damage and various cancers. Morphological and biochemical changes such as energy dependent mechanism plays a pivotal role in apoptosis or PCD(programmed cell death). It has a significant role in development of embryos, normal and proper cell turnover, homeostasis and its functioning. By this process atrophy of a cell occurs which may be hormone dependent or by chemicals. Due to disturbance in apoptosis or failure of regulation of apoptotic signals may lead to condition like damage of neurons, heart, blood regulation, autoimmune disorders or cancers. Study of apoptosis might play a vast development and acknowledgment of the huge therapeutic and palliative aspects of this. Many researches are going on for to understand thoroughly the mechanism of cell cycle and its pathways that is the key regulator of the ...

… journal of oncology, 2002

Cell death and the subsequent post-mortem changes, called necrosis, are integral parts of normal development and maturation cycle. Despite the importance of this process, the mechanisms underlying cell death are still poorly understood. In the recent literature, cell death is said to occur by two alternative, opposite modes: apoptosis, a programmed, managed form of cell death, and necrosis, an unordered and accidental form of cellular dying. The incorrect consequence is the overlapping of: a) the process whereby cells die, cell death; and b) the changes that the cells and tissues undergo after the cells die. Only the latter process can be referred to as necrosis and represents a 'no return' process in cell life. In this review, we discuss the excellent basic research developed in this field during last decades and problems that remain to be resolved in defining both experimentally and mechanicistically the events that lead to and characterize cell death. inflammation and disturbed blood supply (1,2). Cell death is an important variable in cancer development, cancer prevention and cancer therapy (3-5). In the treatment of cancer, the major approach is the removal, by surgery, of the neoplasm and/or the induction of cell death in neoplastic cells by radiation, toxic chemicals, antibodies and/or cells of the immune system (6-9). On the other hand, this pathobiological process remains poorly understood and the physiological and biochemical factors that lead to cell death are still not clear. One main factor is the existing confusion between 'apoptosis' process, as compared and contrasted with 'necrosis', leading to the overlapping of the ante mortem changes, i.e. the process of cell death, and the post-mortem changes, i.e. the necrosis process.

Archives of Surgery, 1998

urrently there is much interest and excitement in the understanding of how cells undergo the process of apoptosis or programmed cell death. Understanding how, why, and when cells are instructed to die may provide insight into the aging process, autoimmune syndromes, degenerative diseases, and malignant transformation. This review focuses on the development of apoptosis and describes the process of programmed cell death, some of the factors that incite or prevent its occurrence, and finally some of the diseases in which it may play a role. The hope is that in the not too distant future we may be able to modify or thwart the apoptotic process for therapeutic benefit.

Nature Reviews Molecular Cell Biology, 2001

PERSPECTIVES research into caspases and the role of mitochondria in apoptosis -are mentioned only briefly.

European Respiratory Journal, 1996

Three steps can be distinguished in the pathway that leads to cell death.

Asian Journal of Animal and Veterinary Advances, 2015

The normal cell has its own homeostatic mechanism. A slight deviation in this mechanism leads firstly to an adaptive response in the form of hypertrophy, atrophy etc. But sometimes when adaptive response exceeds a limit also culminates to cell injury which ultimately leads to cell death. Irreversible form of cell injury leads to cell death in the form of necrosis, apoptosis and autophagy and by other alternative ways of necroptosis, anoikis, entosis and cornification. Necrosis and apoptosis are main mechanisms of cell death in mammalian cells. Necrosis is accidental, uncontrolled and un-programmed cell death which leads to cellular swelling, pyknosis, karyolysis, karyorrhexis, disruption of cell membrane and inflammation. Apoptosis is a programmed and energy dependent pathophysiological phenomenon leading to cellular shrinkage but no cell membrane rupture and no inflammatory response. Apoptosis can be mediated by extrinsic, intrinsic and perforin/granzyme pathways, leading to activation of execution caspases and finally protein cleavage, cross linking and DNA-fragmentation. Extrinsic pathway involve ligand (FasL, TNFα) and receptors (FasR, TNFR) interaction which bind to adapter proteins Fas Associated Death Domain (FADD) and TNFα Receptor Associated Death Domain (TRADD) with activation of initiator caspases-8. Intrinsic pathway involves cytochrome c release along with pro-apoptotic proteins and inhibits anti-apoptotic proteins, leads to cytochrome c interaction with Apaf-1, thus activation of pro-caspase-9. Overall, cell death have clarified many aspects of this fundamental process and brought to the attention of scientists its role in a large number of different diseases. The present review describes apoptosis and other alternate mechanisms of cell death with biomedical and veterinary perspectives.

International Journal of Livestock Research, 2017

Apoptosis, a Programmed Cell Death (PCD), specifically refers to an energy-dependent, genetically controlled process by which unnecessary or damaged single cells self-destruct when the apoptosis genes are activated. The role of apoptosis in physiology is as significant as that of its counterpart, mitosis. It helps in maintaining cellular homeostasis in the animal body. The number of cells increase or decrease when there is alteration in apoptosis during normal development and aging or during disease. Abnormalities in cell death regulation may cause diseases/conditions. Some conditions are caused due to insufficient apoptosis whereas others due to excessive apoptosis. Presently, large numbers of synthetic and natural compounds have been discovered to be effective against certain diseases through the induction of apoptosis in their target cells.

Cell Biochemistry and Function, 2011

The literature on apoptosis has grown tremendously in recent years, and the mechanisms that are involved in this programmed cell death pathway have been enlightened. It is now known that apoptosis takes place starting from early development to adult stage for the homeostasis of multicellular organisms, during disease development and in response to different stimuli in many different systems. In this review, we attempted to summarize the current knowledge on the circumstances and the mechanisms that lead to induction of apoptosis, while going over the molecular details of the modulator and mediators of apoptosis as well as drawing the lines between programmed and non-programmed cell death pathways. The review will particularly focus on Bcl-2 family proteins, the role of different caspases in the process of apoptosis, and their inhibitors as well as the importance of apoptosis during different disease states. Understanding the molecular mechanisms involved in apoptosis better will make a big impact on human diseases, particularly cancer, and its management in the clinics.

2005

The fact that cell death is not ultimately a bad thing came as a surprise to many researchers. Physiological cell death has been observed in various multicellular organisms. Apoptosis or programmed cell death is the predominant form of physiological cell death by which the organism eliminates unnecessary or damaged single cells. It is a major component of normal development and disease. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change to assure that apoptotic cells will be immediately recognized and engulfed by neighboring cells or phagocytes leading to little or no inflammation. A wide variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Death receptors that initiate apoptosis include the Fas receptor and the TNF receptor systems. After an appropriate stimulus, the first stage of apoptosis or "decision phase" is the genetic control point of cell death. This is followed by the second stage or "execution phase", which is responsible for the morphological change in apoptosis. The third stage is engulfment of the dying cell followed by degradation of the engulfed cell DNA. There are two overlapping signaling pathways leading to apoptosis, termed the intrinsic and extrinsic pathways. In the intrinsic, various stimuli, such as oxidative stress, lead to mitochondrial dysfunction and the release of pro-apoptotic factors. Ligand binding to cell surface death receptors, such as Fas, activates the extrinsic pathway. During the last decades the molecular mechanisms involved in disordered apoptosis were unraveled, suggesting that cancer, chronic disease, and fetal developmental abnormalities can occur as a result of disordered apoptosis.

Toxicologic pathology, 2007

Cell Death and Differentiation, 2004

ChemBioChem, 2004

Journal of Research and Practice in Dentistry, 2014

Apoptosis is considered as a tightly regulated active process signified by specific morphological and biochemical. On contrary to apoptosis, necrosis is a passive, energy independent pathologic process. The significance of understanding the apoptosis cascade mechanism is imperative as apoptosis being component of both physiological and pathological process. Apoptosis can be stimulated by both physiological and pathological conditions and hence play a role in maintenance of normal homeostasis and in pathogenesis of several diseases. Signaling for apoptosis occurs via caspase dependent and independent pathways that are initiated either from triggering events within the cell or from outside the cell by ligation of death receptors. Present review aims to provide an overview regarding apoptosis, its morphological and biochemical characterstics, its mechanism and its implication in health and diseases.

InTech eBooks, 2013