BCL-2 protein family. Essential regulators of cell death. Preface

ArticleinAdvances in Experimental Medicine and Biology 687:vii-viii · January 2010with1 Reads
Source: PubMed
    • "In rats, Ni deficiency reduces iron content in organs, haemoglobin, and hematocrit [14]. Ni has several biological functions, including activation of calcineurin; action and formation of cGMP [15]; transmission of genetic code (DNA, only anti-apoptotic Bcl-2 protein with three BH domains: BH-1, -2, and -3 [69]. Based on the number of BH domains, pro-apoptotic Bcl-2 family proteins are classified into two subgroups. "
    [Show abstract] [Hide abstract] ABSTRACT: High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity.
    Full-text · Article · Dec 2015
    • "In the mitochondrial pathway, Bax, a pro-apoptotic protein, translocates into the mitochondria and further induces cytochrome c expression, which finally activates caspase cascades , such as caspase-3(Hetz, 2010; Tsujimoto, 2003). Bcl-2, as an anti-apoptotic protein, binds to Bax to form a dipolymer , and the Bax/Bcl-2 ratio suggests pro-apoptotic or antiapoptotic regulation tendency (Hetz, 2010; Tsujimoto, 2003). Our data show that experimental SAH induces the elevation of cleaved caspase-3 and the ratio of upstream Bax to Bcl-2, which represents enhanced mitochondrial-related neuronal apoptosis. "
    [Show abstract] [Hide abstract] ABSTRACT: Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with a reported protective effect against several brain injuries. The current study aimed to investigate the potential of TPM for neuroprotection against EBI after SAH and the possible dose-dependency of this effect. An endovascular perforation SAH model was established in rats, and TPM was administered by intraperitoneal injection after surgery at three different doses (20mg/kg, 40mg/kg, and 80mg/kg). The animals' neurological scores and brain water content were evaluated, and ELISA, Western blotting and immunostaining assays were conducted to assess the effect of TPM. The results revealed that TPM lowers the elevated levels of myeloperoxidase and proinflammatory mediators observed after SAH in a dose-related fashion, and the nuclear factor-kappa B (NF-κB) signalling pathway is the target of neuroinflammation regulation. In addition, TPM ameliorated SAH-induced cortical neuronal apoptosis by influencing Bax, Bcl-2 and cleaved caspase-3 protein expression, and the effect of TPM was enhanced in a dose-dependent manner. Various dosages of TPM also upregulated the protein expression of the γ-aminobutyric acid (GABA)-ergic signalling molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, and K(+)-Cl(-) co-transporter 2 (KCC2) together and downregulated Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1) expression. Thus, TPM may be an effective neuroprotectant in EBI after SAH by regulating neuroinflammation and neuronal cell death. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jun 2015
    • "Release of proteins, such as cytochrome c, along with increased Bax levels results in cell death through increased levels of key caspases. In contrast, B-cell lymphoma-extra large (Bcl-xL), an antiapoptotic member of the Bcl-2 family, is known to prevent cell death by inhibiting activation of the proapoptotic proteins [35,37-39]. These changes have been well studied in other diseases, as well as other cell types in diabetic retinopathy [34,36]. "
    [Show abstract] [Hide abstract] ABSTRACT: To determine whether β-adrenergic receptors require insulin receptor substrate (IRS)-1 activity to regulate apoptosis in retinal Müller cells. Müller cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) medium grown in normal (5 mm) or high glucose (25 mM) conditions. The medium was supplemented with 10% fetal bovine serum and antibiotics. Cells were allowed to reach 80%-90% confluence. After becoming appropriately confluent, cells were placed in medium with reduced serum (2%) for 18-24 h to eliminate any effects of fetal bovine serum. Cells were then transfected with 10 ug of IRS-1 small hairpin RNA (shRNA). Forty-eight hours following transfection, cells were lysed and harvested for protein analysis using western blotting. In additional experiments, some cells were treated with 10 uM salmeterol for 24 h following transfection with IRS-1 shRNA. To determine whether IRS-1 directly regulates apoptotic events in the insulin-signaling pathway in retinal Müller cells, a cell death assay kit was used. In tumor necrosis factor (TNF)α inhibitory studies, cells were treated with 5 ng/ml of TNFα alone for 30 min or 30 min pretreatment with TNFα followed by salmeterol for 4 h. Müller cells treated with 5 ng/ml TNFα in 25 mM glucose significantly increased phosphorylation of IRS-1(Ser307). Treatment with the selective beta-2-adrenergic receptor agonist, salmeterol, significantly decreased phosphorylation of IRS-1(Ser307). Following IRS-1 shRNA transfection+salmeterol treatment, Bcl-2-associated X protein (Bax) and cytochrome c levels were significantly decreased. Salmeterol+IRS-1 shRNA also decreased cell death and increased protein levels of B-cell lymphoma-extra large (Bcl-xL), an anti-apoptotic factor. In these studies, we show for the first time that salmeterol, a beta-2-adrenergic receptor agonist, can reduce retinal Müller cell death through IRS-1 actions. These findings also suggest the importance of IRS-1 in beta-adrenergic receptor signaling in the prevention of cell death in retinal Müller cells.
    Full-text · Article · Feb 2012
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