Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive programmed cell death (PCD) is initiated at the onset of amphibian metamorphosis, resulting in 100% of cells dying in some larval tissues, as during total regression of tail and gills. All cell death during metamorphosis is under the control of thyroid hormone (TH), which can initiate the process precociously in whole tadpoles or in individual tissues in culture. The hormone prolactin (PRL), given exogenously, prevents natural and TH-induced metamorphosis. We have exploited this dual hormonal regulation in premetamorphic Xenopus tails in organ culture to identify and characterize early genes that are TH-induced and considered important for initiating cell death. Among the earliest genes activated by TH are those encoding the two thyroid hormone receptors TR alpha and TR beta. This autoinduction of TR genes is considered important since, in blocking this process, PRL also inhibited the expression of other TH-inducible genes and prevented cell death. The expression of early genes other than TR genes, which are known to promote cell death or survival, is also considered to be important for the initiation of PCD during amphibian metamorphosis. We are, therefore, working on the identification, characterization, and expression of members of the Xenopus bcl-2-like gene family, as well as other genes, such as nur-77 and ICE, which may act as early genes during tadpole tail regression.
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PMID:Hormonal regulation of programmed cell death during amphibian metamorphosis. 765 31

The c-erbA protooncogene encodes the thyroid hormone (3,5,3'-triiodothyronine; T3) receptor alpha1 (TR alpha1). c-erbA/TR alpha1 is expressed in many cell types including glial cells, particularly in the immature state. We show here by morphological and biochemical criteria that c-erbA induces apoptosis of glial B3.1 cells in serum-deprived conditions. This effect is mostly T3 independent. Growth factors such as platelet-derived growth factor, basic fibroblast growth factor, or transforming growth factor-alpha prevent B3.1 + TR alpha1 cell death. Protein kinase C (PKC) activators also prevent the apoptosis phenomenon, an effect that was blocked by the PKC-specific inhibitor GF109203X. Expression of an exogenous bcl-2 gene led also to B3.1 + TR alpha1 cell survival. Neither a series of inhibitors including GF109203X nor T3 inhibits bcl-2 action, indicating that bcl-2 blocks a downstream step in the death-promoting process. B3.1 + TR alpha1 cell apoptosis is not blocked by caspase-1 or poly-ADP-ribosyltransferase inhibitors, suggesting that the activation of these classic pathways is not involved in the apoptotic mechanism. In addition, direct interaction with specific neuronal cells but not incubation with their conditioned medium inhibits also apoptosis of B3.1 + TR alpha1 cells. Our results show that c-erbA promotes an apoptotic process in glial B3.1 cells that is suppressible by PKC activation and bcl-2, probably by distinct mechanisms.
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PMID:The c-erbA alpha protooncogene induces apoptosis in glial cells via a protein kinase C- and bcl-2-suppressible mechanism. 960 96

Caspases, a family of cysteine proteases, have been recognized as the central executors of programmed cell death. Nonetheless, the information on the caspase family has been limited to mammals, Drosophila, and nematodes. To examine the structure and characterization of the Xenopus caspase family, we have cloned the cDNAs encoding caspase-2 and -6-10 in addition to caspase-1 and -3, which we characterized previously (Yaoita, Y., and Nakajima, K. (1997) J. Biol. Chem. 272, 5122-5127). First, the existence of these caspases in frog suggests that the caspase cascades clarified in mammals are conserved at least from Amphibia. Interestingly, Xenopus caspase-1, -8, and -10 (especially caspase-8) showed a lower degree of identity to human equivalents than the other caspases. Second, mRNAs of many caspases increased during the climax of metamorphosis in regressing organs, tail, and intestine, where programmed cell death occurs, but not in apoptotic tail-derived cultured cells (XLT-15-11) treated with thyroid hormone, showing that new RNA synthesis of caspases is dispensable to programmed cell death. Third, comparison of human and Xenopus caspase sequences implies that some proposed regulations of human caspases are not conserved in frog.
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PMID:Structure, expression, and function of the Xenopus laevis caspase family. 1074 39

The thyroid hormone, 3,3,5-triiodo-L-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta.
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PMID:Biological functions of thyroid hormone in placenta. 2569 32