Role of genes involved in the regulation of apoptosis in the pathogenesis of genital endometriosis. A literature review

BACKGROUND: The high prevalence, the lack of reliable data on the etiology, as well as the complexity of diagnosis and treatment of genital endometriosis indicate the urgency of the problem. AIM: The aim of this study was to analyze and summarize scientific publications devoted to the study of single-nucleotide polymorphisms involved in apoptosis and their association with endometriosis. MATERIALS AND METHODS: Based on keyword searches for gene, SNP, apoptosis, and endometriosis, a selection of papers published in open sources (PubMed and Google Scholar) in the period from 2010 to 2020 was performed. RESULTS AND CONCLUSIONS: An analysis of the main and auxiliary apoptotic pathways was performed, with the protein regulators and their genes detailed in accordance with the implementation of the programmed cell death cascade in genital endometriosis. The review identified the significance of a number of proteins (TNF-, FADD, CASP3, CASP7, CASP10) in the pathogenesis of hyperproliferative diseases. However, many apoptotic regulators (BCL2, BIK, BMF, HRK, BAD, Survivin) in genital endometriosis were found to have been understudied, which makes future research in this direction promising.

Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells

A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states.

Blockage of NOX2/MAPK/NF-κB Pathway Protects Photoreceptors against Glucose Deprivation-Induced Cell Death

Acute energy failure is one of the critical factors contributing to the pathogenic mechanisms of retinal ischemia. Our previous study demonstrated that glucose deprivation can lead to a caspase-dependent cell death of photoreceptors. The aim of this study was to decipher the upstream signal pathway in glucose deprivation- (GD-) induced cell death. We mimicked acute energy failure by using glucose deprivation in photoreceptor cells (661W cells). GD-induced oxidative stress was evaluated by measuring ROS with the DCFH-DA assay and HO-1 expression by Western blot analysis. The activation of NOX2/MAPK/NF-κB signal was assessed by Western blot and immunohistochemical assays. The roles of these signals in GD-induced cell death were measured by using their specific inhibitors. Inhibition of Rac-1 and NOX2 suppressed GD-induced oxidative stress and protected photoreceptors against GD-induced cell death. NOX2 was an upstream signal in the caspase-dependent cell death cascade, yet the downstream MAPK pathways were activated and blocking MAPK signals rescued 661W cells from GD-induced death. In addition, GD caused the activation of NF-κB signal and inhibiting NF-κB significantly protected 661W cells. These observations may provide insights for treating retinal ischemic diseases and protecting retinal neurons from ischemia-induced cell death.

Role of Melatonin in Reducing Amphetamine-Induced Degeneration in Substantia Nigra of Rats via Calpain and Calpastatin Interaction

Excessive intracellular calcium levels induce calpain activation, thereby triggering the cell death cascade. Several lines of evidence have demonstrated the neuroprotective role of the overexpression of calpain inhibitor, calpastatin. In this study, amphetamine-induced degeneration in the substantia nigra of rats was determined by evaluating the decrease in the levels of tyrosine hydroxylase phosphorylation. Amphetamine significantly decreased calpastatin levels but increased calpain levels. An induction in calpain activity was demonstrated by an increase in the formation of calpain spectrin breakdown products. The deleterious effects of amphetamine exposure were diminished in rats by pretreatment with melatonin. In addition, the effect of melatonin on calpastatin expression was investigated in human neuroblastoma SH-SY5Y cells. Melatonin was able to increase the calpastatin levels, and this effect could be blocked by luzindole, a melatonin receptor antagonist. These results demonstrate the neuroprotective ability of melatonin and its role in inducing calpastatin expression via a receptor-dependent pathway.

Two Close, Too Close

Mitochondria are key organelles in cell life whose dysfunction is associated with a variety of diseases. Their crucial role in intermediary metabolism and energy conversion makes them a preferred target in tissues, such as the heart, where the energetic demands are very high. In the cardiomyocyte, the spatial organization of mitochondria favors their interaction with the sarcoplasmic reticulum, thereby offering a mechanism for Ca 2+ -mediated crosstalk between these 2 organelles. Recently, the molecular basis for this interaction has begun to be unraveled, and we are learning how endoplasmic reticulum–mitochondrial interactions are often exploited by death signals, such as proapoptotic Bcl-2 family members, to amplify the cell death cascade. Here, we review our present understanding of the structural basis and the functional consequences of the close interaction between sarcoplasmic reticulum and mitochondria on cardiomyocyte function and death.