Azoramide improves mitochondrial dysfunction in palmitate-induced insulin resistant H9c2 cells

Molecular and Cellular Biochemistry - White adipose tissue (WAT) is the bulk of fatty tissues in humans. Enhancing the potential of WAT-derived stem cells (WATDCs) to generate cardiomyocytes may...     

Lack of a time-dependent effect of melatonin on radiation-induced apoptosis in cultured rat lymphocytes

Ionizing radiation is widely used for the treatment of solid tumors and it is thought to act by directly targeting tumor clonogens, also known as stem cells. Apoptosis is a genetically programmed mechanism of cell death often characterized by internucleosomal DNA cleavage. Although it has been previously shown that lymphocytes readily undergo apoptosis in patients receiving anticancer drugs or treatment with ionizing radiation, this is the first study to investigate the influence of radiotherapy and melatonin on apoptosis in rat lymphocytes at two different times of the day. Melatonin, a free radical scavenger, is an endogenous neurohormone predominantly synthesized in and secreted by the pineal gland. It has been shown that melatonin inhibits apoptosis in normal cells but it increases the rate of apoptosis in various cancer cells. Therefore, in the present study, the effect of melatonin on apoptosis in cultured lymphocytes was studied after total body irradiation (TBI) was given to rats in the morning (1 HALO) or evening (13 HALO) with morphological and DNA fragmentation analysis. Two-way analysis of variance (ANOVA) revealed that radiation increased the rate of apoptosis in rat lymphocytes after TBI, and melatonin treatment did not reduce the rate of apoptosis after TBI at either time point. We conclude that the lack of an effect of melatonin on the apoptosis rate in rat lymphocytes might be due to the dose-dependent effect of melatonin, the time course of apoptosis investigated, or the cell type in which apoptosis was examined.     

Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells

Doxorubicin (DOXO), a widely used chemotherapeutic agent, induces apoptosis in transformed and non-transformed cells. The apoptotic effect of DOXO has been linked to the generation of reactive oxygen species (ROS). Antioxidants may be effective in the prevention of DOX-induced apoptosis. In the present study we investigated the effects of stobadine, a pyridoindole antioxidant in a DOXO-induced apoptosis model of P815 cells by flow cytometric analyses and by measuring caspase-3 and caspase-9 activities. Pretreating cells with stobadine significantly increased cell viability and decreased apoptosis rate. Inhibition in apoptosis was observed at maximum levels following treatment of cells with 10(-7)M stobadine as evident from flow cytometric analyses. The antiapoptotic effect of stobadine was further confirmed by inhibition of caspase-3 and caspase-9 activities. We found that the antioxidative effects of stobadine were comparable to the effects of a well known antioxidant, N-acetyl l-cysteine (NAC).     

The effect of clopidogrel on apoptosis--an in vivo study

Clopidogrel is widely used in cardiovascular medicine, and is believed to play an important role in the pathogenesis of many cardiovascular disease processes. In particular, patients undergoing coronary stenting, who are commonly treated with clopidogrel, are candidates for in-stent restenosis. This is mainly caused by neointimal hyperplasia, so it is important to consider whether clopidogrel affects neointimal hyperplasia via apoptosis. Lymphocytes, especially T-cells, are known to play a key role in the initiation and formation of atherosclerotic plaques. The aim of this study was to investigate the effect of clopidogrel on human lymphocyte apoptosis, using a DNA fragmentation assay.     

Structure of the C-terminal half of UvrC reveals an RNase H endonuclease domain with an Argonaute-like catalytic triad

Removal and repair of DNA damage by the nucleotide excision repair pathway requires two sequential incision reactions, which are achieved by the endonuclease UvrC in eubacteria. Here, we describe the crystal structure of the C-terminal half of UvrC, which contains the catalytic domain responsible for 5' incision and a helix-hairpin-helix-domain that is implicated in DNA binding. Surprisingly, the 5' catalytic domain shares structural homology with RNase H despite the lack of sequence homology and contains an uncommon DDH triad. The structure also reveals two highly conserved patches on the surface of the protein, which are not related to the active site. Mutations of residues in one of these patches led to the inability of the enzyme to bind DNA and severely compromised both incision reactions. Based on our results, we suggest a model of how UvrC forms a productive protein-DNA complex to excise the damage from DNA.     

Heavy metal risk assessment of European eels (Anguilla anguilla,Linnaeus, 1758) from the Asi (Orontes) River,Turkey

The muscle tissues of a total 154 sampled eels from the Asi (Orontes) River were analyzed between January and December 2018 to determine the content of heavy metals (Hg, Pb, Cd and As). Determination of heavy metals in muscle tissue was carried out with an Inductively Coupled Plasma Mass Spectrometer (ICP-MS). To express the risk level for human consumption of heavy metal contaminated eels we used common concepts and criteria such as Hazard Index (HI), Target Hazard Quotient (THQ) and Total THQ (TTHQ). From the human health point of view, the indices HI, THQ, TTHQ values of Hg, Cd, Pb and As indicate no risks for the consumers at assumed intake levels per unit time.