Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The process of apoptosis in immune cells like mast cells is essential to regain homeostasis after an inflammatory response. The intrinsic pathway of apoptosis is ultimately controlled by the pro-apoptotic Bcl-2 family members Bax and Bak, which upon activation oligomerize to cause increased permeabilization of the mitochondria outer membrane leading to cell death. We examined the role of Bax and Bak in cytokine deprivation-induced apoptosis in mast cells using connective tissue-like mast cells and mucosal-like mast cells derived from bax(-/-), bak(-/-) and bax(-/-)bak(-/-) mice. Although both Bax and Bak were expressed at readily detectable protein levels, we found a major role for Bax in mediating mast cell apoptosis induced by cytokine deprivation. We analyzed cell viability by propidium iodide exclusion and flow cytometry after deprivation of vital cytokines for each mast cell population. Upon cytokine withdrawal, bak(-/-) mast cells died at a similar rate as wild type, whereas bax(-/-) and bax(-/-)bak(-/-) mast cells were partially or completely resistant to apoptosis, respectively. The total resistance seen in bax(-/-)bak(-/-) mast cells is comparable with mast cells deficient of both pro-apoptotic Bim and Puma or mast cells overexpressing anti-apoptotic Bcl-2. These results show that Bax has a predominant and Bak a minor role in cytokine deprivation-induced apoptosis in both connective tissue-like and mucosal-like mast cells.
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PMID:Pro-apoptotic Bax is the major and Bak an auxiliary effector in cytokine deprivation-induced mast cell apoptosis. 2136 49

Reovirus is a potent oncolytic virus in many human neoplasms that has reached phase II and III clinical trials. Our laboratory has previously reported the oncolytic effects of reovirus in canine mast cell tumour (MCT). In order to further explore the potential of reovirus in veterinary oncology, we tested the susceptibility of reovirus in 10 canine lymphoma cell lines. Reovirus-induced cell death, virus replication and infectivity were confirmed in four cell lines with variable levels of susceptibility. The level of Ras activation varied among the cell lines with no correlation with reovirus susceptibility. Reovirus-susceptible cell lines underwent apoptosis as proven by propidium iodide (PI) staining, Annexin V-FITC/PI assay, cleavage of PARP and inhibition of cell death by caspase inhibitor. A single intratumoral injection of reovirus suppressed the growth of canine lymphoma subcutaneous tumour in NOD/SCID mice. Unlike canine MCT, canine lymphoma is less susceptible to reovirus.
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PMID:The effects of oncolytic reovirus in canine lymphoma cell lines. 2531 93

One key characteristic of certain mast cell populations is their longevity. Mast cell survival can also be promoted by Fc-receptor activation. Regulation of cell survival and apoptosis is regulated by the Bcl-2 family that consists of pro- and anti-apoptotic proteins. Depending on their relative cellular expression levels, the cells are either rescued or destined for apoptosis. To determine the regulation of mast cell survival and apoptosis, the expression of different Bcl-2 protein family members can be measured by western blot. The amount of viable versus apoptotic cells is decided by AnnexinV/propidium iodide staining, and cell lysates are prepared for western blot analysis from the appropriated time points.
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PMID:Regulation of mast cell survival and apoptosis. 2538 56


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