scholarly journals Mitochondrial medicine - a key to solve pathophysiology of 21 century diseases

2008 ◽  
Vol 2 (1-2) ◽  
pp. 46-48
Author(s):  
Emina Kiseljaković ◽  
Radivoj Jadrić ◽  
Sabaheta Hasić ◽  
Lorenka Ljuboja ◽  
Jovo Radovanović ◽  
...  

Over the past 13 years mitochondrial defects have been involved in wide variety of degenerative diseases - Parkinson disease, Alzheimer dementia, arteriosclerosis, ageing and cancer. Mitochondria are believed to control apoptosis or programmed cell death. Disturbance in mitochondrial metabolism has also been implicated in many common diseases such as congestive hart failure, diabetes and migraine. Scientific investigations have showed complexities in mitochondrial genetics, but at the same time, pathophysiology of mitochondrial diseases is still enigma. Mitochondria and their DNAs are opening the era of "mitochondrial medicine". What we today call "a mitochondrial medicine" is only a part of the whole panorama of diseases based on disordered mitochondrial function.

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1089
Author(s):  
Huimin Ren ◽  
Xiaohong Zhao ◽  
Wenjie Li ◽  
Jamshaid Hussain ◽  
Guoning Qi ◽  
...  

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.


1998 ◽  
Vol 4 (4) ◽  
pp. 301-311 ◽  
Author(s):  
Robert E. Burke

Degenerative disorders of the basal ganglia are characterized by disturbances of motor control. Prototypic examples are Parkinson's disease, which is caused by degeneration of dopamine neurons of the substantia nigra, and Huntington's disease, which is caused by degeneration of neurons of the striatum. In recent years, it has been postulated that some of these disorders may be caused by programmed cell death or apoptosis, a genetically regulated form of cell death. There is clear evidence that apoptosis occurs in neurons of the basal ganglia during normal development, that it can be regulated, and that it can be induced in some animal models of these disorders. Although there is some suggestive direct evidence that apoptosis may occur in the human brain in these disorders, the evidence to date is partial and not yet compelling. Nevertheless, programmed cell death is an important new hypothesis for the pathogenesis of these disorders and warrants vigorous further investigation, particularly with molecular markers in addition to classic morphological markers. The concept of programmed cell death is relevant not only to the pathogenesis of these diseases but also to therapeutic issues, such as transplantation approaches.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A921-A922
Author(s):  
Ada Marie Santiago Carrion ◽  
Yanerys Agosto-Vargas

Abstract Cluster of differentiation 52 (CD-52) is a glycoprotein expressed on the surface of most lymphocytes and it is the most prevalent marker in T cells, B cells, natural killers and monocytes. Alemtuzumab, a CD-52 monoclonal antibody, is one of the initial therapies approved for patients with relapsing-remitting multiple sclerosis. It acts by inducing rapid and prolonged depletion of lymphocytes with a consequent immunosuppression. Although not clearly understood, Alemtuzumab has been associated with the development of autoantibodies. These have been reported to cause thyroid injury resulting in 10-15% incidence of new-onset Graves’ disease. This is the case of a 38 year-old man with medical history of relapsing-remitting multiple sclerosis who came to the Endocrinology clinic to establish care due to abnormal thyroid function tests. Patient has received Alemtuzumab since the past two years. Three months prior to arrival, he was found with weight loss, hyperdefecation and tremors by his Neurologist. Patient was found with suppressed TSH for which Methimazole was commenced. Thyroid ultrasound showed normal size and homogenous right and left thyroid lobes, and no evidence of cystic or solid masses. Thyroid stimulating immunoglobulins were found elevated which correlated with Graves’ disease. Moreover, thyroid scintigraphy showed 34% radioiodine uptake at 24 hours indicating de novo synthesis of thyroid hormone in this patient with hyperthyroidism. As Alemtuzumab was identified as a precipitating cause of Graves’ disease, therapy was discontinued and plasmapheresis will be given for the treatment of relapsing-remitting multiple sclerosis. Monoclonal antibody use has increased since the past decades. It has been well described in literature that monoclonal antibodies against programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) may cause autoimmune thyroid disease. Nonetheless, it is important to recognize that other monoclonal antibodies may have similar adverse effects. Alemtuzumab is a monoclonal antibody and antineoplastic agent used for relapsing multiple sclerosis, some hematologic malignancies, and as an induction agent for solid organ transplantation. Its main effects include autoimmunity with thyroid being one of the most described targets. In these patients, expert clinicians should recognize the possibility of thyroid disease for prompt treatment which will improve quality of life.


2006 ◽  
Vol 84 (2) ◽  
pp. 307-321 ◽  
Author(s):  
M Wiens ◽  
W E.G Müller

Apoptosis represents the morphological manifestation of programmed cell death and, paradoxically at first sight, it is a prerequisite for metazoan life. Thus, apoptosis is responsible for the demise of cells during many physiological processes. It is also accountable for the death of cells following exposure to countless stimuli. Therefore, it is obvious that apoptosis must be regulated by a complex network of various molecular signaling pathways. Research during the past 20 years has led to the identification of major functional groups of molecules involved in apoptotic pathways. These include members of the Bcl-2 superfamily, members of the TNF family, caspases, and their activators. Yet, the evolutionary conservation of those elements of the apoptotic machinery was only established from nematode to man. Sponges (phylum Porifera) are characterized by a remarkable regeneration capacity and longevity. Furthermore, they represent the phylogenetically oldest still extant metazoan taxon. Thus, research on these living fossils opens a window to the past, to the dawn of metazoan life. It allows us to trace the evolution of programmed cell death and its core components. This review summarizes the key findings and concepts which have emerged from studies of apoptosis in Porifera.


2007 ◽  
Vol 27 (1-3) ◽  
pp. 1-3
Author(s):  
Luigi Murri

Mitochondrion is currently known to play major roles in many disease processes: neuromuscular disorders, neurodegenerative conditions (i.e. Parkinson's and Alzheimer's diseases), diabetes mellitus, aging, programmed cell death, and carcinogenesis, to name a few. In this background, the Department of Neuroscience of the University of Pisa (Italy) has organised a scientific meeting on October 25th, 2006, to discuss recent progress in the field of mitochondriology.


2020 ◽  
Vol 7 (2) ◽  
pp. 92-108
Author(s):  
E. M. Frantsiyants ◽  
I. V. Neskubina ◽  
E. A. Sheiko

Mitochondria are intracellular organelles in eukaryotic cells that participate in bioenergy metabolism and cell homeostasis, including ATP generation through electron transport and oxidative phosphorylation in combination with oxidation of metabolites by the tricarboxylic acid cycle and fatty acid catabolism via β-oxidation. the production of reactive oxygen species, as well as the initiation and implementation of apoptosis. Mitochondria play a crucial role in cellular energy metabolism and the regulation of programmed cell death. mitochondria activate numerous signaling pathways associated with cell death. Mitochondria have the ability to control the activation of programmed cell death by regulating the translocation of proapoptotic proteins from the intermediate space of mitochondria to the cytosol. This is the reason for the emergence of a new discipline — mitochondrial medicine. The review examined and analyzed scientific publications on the role of mitochondria in the life support of transformed cells, the study of their functioning and structurally functional dysfunctions, as part of mitochondrial medicine. Mitochondrial medicine is a developing discipline whose significance stems from the central function of mitochondria in the production of adenosine triphosphate, the generation of reactive oxygen species, and cell death due to necrosis or apoptosis. Consequently, mitochondrial dysfunction plays an important role in the pathophysiology of cancer, many other common diseases and side effects of drugs. Perhaps the combined use of modulators of mitochondrial metabolism and antitumor therapy will contribute to the emergence of a new direction in antitumor treatment, which will significantly increase the effectiveness of cancer treatment.


2019 ◽  
Author(s):  
P. Seyed Mir ◽  
A.-S. Berghoff ◽  
M. Preusser ◽  
G. Ricken ◽  
J. Riedl ◽  
...  

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.


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