Mechanism Of Mitochondrial Apoptosis Research Articles

Chronic neurogenic pain inducing chemiluminescence of mitochondrial associates in cardiomyocytes.

e21560 Background: Mitochondrial dysfunction is has a significant impact on the development of heart disease and is a characteristic feature of the heart physiopathology. Our purpose was to analyze some mechanisms of apoptosis regulation and self-organization in the mitochondria of the heart cells in mice with melanoma growing in presence of chronic neurogenic pain (CNP). Methods: The study included female C57BL/6 mice (n = 105) divided into groups: intact animals (n = 21); controls (C, n = 21) with a CNP model created by bilateral sciatic nerve ligation under xylazine/zoletil anesthesia; main group (CNP+B16/F10, n = 63) with B16/F10 melanoma transplanted after CNP creation. After decapitation, mitochondria of the heart were isolated by differential centrifugation. Levels of cytochrome C (ng/mg of protein), caspase 9 (ng/mg of protein), Bcl-2 (ng/mg of protein), AIF (ng/mg of protein), Ca2+ (mmol/g of protein) were determined in mitochondrial samples by ELISA. Results: CNP downregulated levels of Ca2+ by 3.2 times, Bcl-2 by 1.3 times (p < 0.05) and caspase 9 by 1.5 times (p < 0.05), compared to intact mice. AIF levels, on the contrary, were elevated by 2.3 times, and cytochrome C did not differed statistically significantly from intact values. After a week of B16/F10 growth in presence of CNP, levels of Ca2+ in the mitochondria of the heart increased by 5.3 times relative to C values. Further on, Ca2+ decreased to almost undetectable values. The AIF levels changed abruptly: after 1 week it increased by 3.7 times, after 2 weeks it declined to C levels, and after 3 weeks it became 5.2 times lower than in C and 2.3 times lower than in intact animals. Bcl-2 and cytochrome C changed similarly: Bcl-2 after 1 week of melanoma growth in presence of CNP increased 1.7 times (p < 0.05) compared to C, and then after 2-3 weeks it declined and became on average 2.2 times lower than in the mitochondria of the C group; levels of cytochrome C after 1 week did not differed significantly from the values in C, and after 2-3 weeks they decreased by 2.2 times. The levels of caspase 9 in CNP+B16/F10 were on average 2.4 times higher than C values throughout the study. The cold light of high brightness - chemiluminescence was recorded in samples of mitochondrial suspension after 2-3 weeks of CNP+B16/F10. The glow in heart mitochondrial samples was accompanied by bright flashes and a 10-15 second intense white glow with a gradual fading and settling of a large filamentous aggregation of mitochondria on the substrate layer. CNP contributed to the energy supply system blocking in the energy systems of cardiomyocytes. Conclusions: Mitochondrial mechanisms of apoptosis and self-organization of subcellular energy structures in the conditions of malignant tumor growth in presence of CNP are mediated by disruption of polyenzymatic apoptosis regulation systems, and a high level of oxidative stress that induces chemiluminescence of cardiomyocyte mitochondrial associates.

Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases.

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

Effects of lysosomal iron involvement in the mechanism of mitochondrial apoptosis on postmortem muscle protein degradation

This study investigated the effect of lysosomal iron involvement in the mechanism of mitochondrial apoptosis on bovine muscle protein degradation during postmortem aging. Six crossbred cattle were studied to evaluate intracellular reactive oxygen species (ROS), antioxidant enzyme activity, lysosomal membrane stability, mitochondrial dysfunction-induced apoptosis, desmin and troponin-T degradation in both control and iron chelator desferrioxamine (DFO) groups. Results showed that lysosomal iron induced ROS accumulation and lysosomal membrane destabilization by decreasing the antioxidant enzyme activity (P < 0.05). Subsequently, lysosomal dysfunction mediated by iron increased mitochondrial membrane permeability and decreased mitochondrial membrane potential, thereby enhancing Bid and cytochrome c release and caspase-9/-3 activation (P < 0.05). Ultimately, lysosomal iron mediated lysosomal-mitochondrial apoptosis increased the postmortem bovine muscle desmin and troponin-T degradation (P < 0.05). The results indicated that lysosomal iron contributes to postmortem meat tenderization through the lysosomal-mitochondrial dysfunction-induced apoptosis pathway.

Mitochondrial mechanisms of apoptosis in case of experimental combined trauma of the chest and both thighs

Mitochondrial mechanisms of apoptosis in case of experimental combined trauma of the chest and both thighs

Mitochondrial mechanisms of apoptosis in case of experimental combined trauma of the chest and both thighs

Mitochondrial mechanisms of apoptosis in case of experimental combined trauma of the chest and both thighs

Mitochondrial mechanisms of apoptosis in response to DNA damage

Integrity of genome is a prerequisite for cell viability. Therefore, targeted damage of DNA structure is considered the key approach to the induction of cell death. Among the plethora of death execution programs the mitochondrial events are of the utmost importance. However, the epigemetic activation of defense mechanisms in response to DNA damage limit cell death. This review analyses the outcome of the genotoxic stress (i.e., cell death versus survival) as a balance of pro- and anti-apoptotic signaling. Practically speaking, the combinations of DNA damaging agents with the inhibitors of anti-apoptosis would increase the efficacy of anticancer therapy.

Modelling of the mitochondrial apoptosis network

In this paper, we performed an experimental observation-based computer simulation of the regulatory network of mitochondrial apoptosis. By modelling we obtained dynamical understandings of various apoptosis-related proteins, including cytochrome c (cyt c) release and caspase activation. Through parameter analysis, we examined the role of Bcl-2 family proteins and the natural inhibitors of apoptosis in the regulatory network of apoptosis. Furthermore, the effects of several amplified loops in the network were found to enhance caspase activation and make the decision of apoptosis switch like. Consistent with most available experimental evidences, our results yield insights into the complex regulatory mechanism of mitochondrial apoptosis.

Mitochondria are involved in the neurogenic neuroprotection conferred by stimulation of cerebellar fastigial nucleus

Activation of neural pathways originating in the cerebellar fastigial nucleus (FN) protects the brain from the deleterious effects of cerebral ischemia and excitotoxicity, a phenomenon termed central neurogenic neuroprotection. The neuroprotection is, in part, mediated by suppression of apoptosis. We sought to determine whether FN stimulation exerts its anti-apoptotic effect through mitochondrial mechanisms. Mitochondria were isolated from the cerebral cortex of rats in which the FN was stimulated for 1 h (100 microA; 1 s on/1 s off), 72 h earlier. Stimulation of the dentate nucleus (DN), a brain region that does not confer neuroprotection, served as control. Mitochondria isolated from FN-stimulated rats exhibited a marked increase in their ability to sequester Ca2+ and an increased resistance to Ca2+-induced membrane depolarization and depression in respiration. FN stimulation also leads to reduction in the release in cytochrome c, induced either by Ca2+ or the mitochondrial toxin mastoparan. Furthermore, in brain slices, FN stimulation reduced the staurosporine-induced insertion of the pro-apoptotic protein Bax into the mitochondria, a critical step in the mitochondrial mechanisms of apoptosis. Collectively, these results provide evidence that FN stimulation protects the mitochondria from dysfunction induced by Ca2+ loading, and inhibits mitochondrial pathways initiating apoptosis. These mitochondrial mechanisms are likely to play a role in the neuroprotection exerted by FN stimulation.