Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poorly controlled diabetes mellitus can result in decreased prolactin production and thus problems with lactation, reproduction, and other physiological processes. This may be due to a loss of lactotrophs, as we have previously shown that long-term (8 weeks) poorly controlled streptozotocin-induced diabetes results in increased death of lactotrophs and that this most likely occurs through the activation of caspase-8 and the extrinsic cell death cascade. However, cell proliferation is also increased in the anterior pituitary at this time, although the cell type undergoing this proliferation and whether it is a response to the increased cell death remains unknown. In order to determine the time-course of increased cell death and proliferation in the anterior pituitary and if this is related to changes in tumor necrosis factor (TNF)-alpha, a cytokine involved in the activation of the extrinsic cell death pathway, rats were killed at 1, 4, 6, and 8 weeks after the induction of diabetes. Cell death was significantly increased after 4 weeks, as was caspase-8 activation, although circulating levels of TNF-alpha were increased as early as 1 week. Pituitary levels of TNF-alpha did not change significantly until 8 weeks after diabetes onset. Similarly, Western-blot analysis of proliferating cell nuclear antigen showed that anterior pituitary cell proliferation increased significantly 8 weeks after diabetes onset, with the majority of proliferating cells, as detected by BrdU incorporation, corresponding to lactotrophs. These results suggest that the increased death of lactotrophs in poorly controlled diabetic rats is followed by increased proliferation of this cell type, even when no treatment is given.
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PMID:Increased apoptosis of lactotrophs in streptozotocin-induced diabetic rats is followed by increased proliferation. 1706 89

Prolactin is a multifaceted hormone that is capable of modulating hundreds of physiological processes in adult vertebrates. However, the physiological functions of prolactin in embryonic development are still controversial. One of these biological functions of prolactin is to promote survival of the cells. Almost all studies on the anti-apoptotic action of prolactin have been focused on a variety of mammalian cell lines and tissues, while no study has been reported on prolactin's anti-apoptotic role in the embryo. In order to determine whether prolactin acts as a survival factor for embryonic cells during development, prolactin protein was knocked-down in zebrafish embryos by microinjection of prolactin-morpholino antisense (PRL-MO). Significant increase in the number of apoptotic cells was observed in embryos treated with PRL-MO compared to control embryos injected with control morpholino or non-injected controls. The number of apoptotic cells increased more significantly between 15 and 35 h post-fertilization in the PRL-MO treated group than that of the control. Interestingly, apoptotic cells were restricted to the central nervous system, particularly in the eyes and brain. Apoptosis of these cells was further demonstrated using the comet assay to detect DNA damage, a hallmark of apoptosis. It was found that the level of DNA damage was dose-dependent on the concentration of PRL-MO injected and consistent with higher levels of nick ends detected by the TUNEL assay in PRL-MO embryos. Further examination of apoptotic genes indicated the transcript of caspase-8, a representative caspase gene of the extrinsic pathway, was much higher in prolactin knockdown embryos than the non-injected control. Together, these results suggest that prolactin acts as a survival factor during zebrafish embryogenesis.
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PMID:Prolactin functions as a survival factor during zebrafish embryogenesis. 1903 87

Poorly controlled diabetes is associated with hormonal imbalances, including decreased prolactin production partially due to increased lactotroph apoptosis. In addition to its metabolic actions, ghrelin inhibits apoptosis in several cell types. Thus, we analyzed ghrelin's effects on diabetes-induced pituitary cell death and hormonal changes. Six weeks after onset of diabetes in male Wistar rats (streptozotocin 70 mg/kg), minipumps infusing saline or 24 nmol ghrelin/day were implanted (jugular). Rats were killed two weeks later. Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations.
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PMID:Ghrelin treatment protects lactotrophs from apoptosis in the pituitary of diabetic rats. 1954 Mar 4