BCL-2 protein family. Essential regulators of cell death. Preface.
Available from: Hongrui Guo
- "In rats, Ni deficiency reduces iron content in organs, haemoglobin, and hematocrit. Ni has several biological functions, including activation of calcineurin; action and formation of cGMP; transmission of genetic code (DNA, only anti-apoptotic Bcl-2 protein with three BH domains: BH-1, -2, and -3.[66,70]. In general, BH3 domain-only proteins suppress Bcl-2 anti-apoptotic proteins and induce apoptosis after lethal stress. "
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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.
Available from: ncbi.nlm.nih.gov
- "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]. "
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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.
Available from: etd.uthsc.edu
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