ABSTRACT
Mitochondrial diseases (MD) are a heterogeneous group of multisystem disorders involving metabolic errors. MD are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystem dysfunction with different clinical courses. Most primary MD are autosomal recessive but maternal inheritance (from mtDNA), autosomal dominant, and X-linked inheritance is also known. Mitochondria are unique energy-generating cellular organelles designed to survive and contain their own unique genetic coding material, a circular mtDNA fragment of approximately 16,000 base pairs. The mitochondrial genetic system incorporates closely interacting bi-genomic factors encoded by the nuclear and mitochondrial genomes. Understanding the dynamics of mitochondrial genetics supporting mitochondrial biogenesis is especially important for the development of strategies for the treatment of rare and difficult-to-diagnose diseases. Gene therapy is one of the methods for correcting mitochondrial disorders.
Subject(s)
Mitochondrial Diseases , Humans , Mitochondrial Diseases/genetics , Mitochondrial Diseases/therapy , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Genetic Therapy , Inheritance PatternsABSTRACT
The stiffness of cell membrane was found to be one of the factors determining resistance of a cell in vitro to antibiotic doxorubicin action. Membranes of surviving cells are negatively charged (-35 - -30 mV) and have high values of stiffness (2.2-5.1 µÐ а) at the doxorubicin concentrations in the medium of 1-500 µg/ml. If the drug concentration and exposure time are being increased, only cells with 'soft' membrane (0.25-1 µÐ а) and positive surface potential (15-29 mV) survive. The data obtained have important prognostic value in studying drug resistance of tumour blood cells and can be used as objective markers of efficiency of the antitumor therapy.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm , Acute Disease , Animals , Biomarkers, Pharmacological/analysis , Cell Membrane/pathology , Cell Survival , Humans , Leukemia/diagnosis , Leukemia/pathology , Membrane Potentials , PrognosisABSTRACT
The influence of aqueous solution of pristine C60 fullerene (C60FAS) on functional activity of lymphocytes from a healthy person was studied for the first time. By means of atomic force microscopy, it was found that C60FAS in a concentration of 0.1 mg/ml increases the stiffness of the lymphocyte membrane by 41% (p < 0.05) and lowers the functional activity of the plasmalemma surface, thereby constraining the use of its membrane material in physiological reactions using a hypotonic model in vitro. However, a cell retains the ability to regulate its volume and demonstrates relative resistance to hypo-osmotic stress. The resistance of lymphocytes in hypo-osmotic medium is facilitated by activation of the nucleus by C60 fullerene particles, which regulates the implementation of two consistent phases of an increase and decrease of cell volume, thereby retaining cell viability. All these indicate the impact of C60 fullerene on the cellular nucleus.