Biomedical subjects

J Egashira

Publications and source records attributed to J Egashira.

3 recordsLinked to original sources

PubMed2001

Caspase-9 processing by caspase-3 via a feedback amplification loop in vivo.

In contrast to the autoprocessing of caspase-9, little is known about the biological significance of caspase-9 processing by caspase-3 via a feedback loop in vivo. We prepared antisera against mouse caspase-9 cleavage sites so that only the activated form of mouse caspase-9 was recognized. Using these antisera and caspase-9- and caspase-3-deficient mouse embryonic fibroblasts, we demonstrated that mouse caspase-9 is initially autoprocessed at D(353) and D(368) at low levels during staurosporine-induced apoptosis, whereupon the D(368) and D(168) sites are preferentially processed over D(353) by activated caspase-3 as part of a feedback amplification loop. Ac-DEVD-MCA (caspase-3-like) and Ac-LEHD-MCA (caspase-9-like) cleavage activities clearly showed that caspase-9 autoprocessing was necessary for the activation of caspase-3, whereas full activation of caspase-3 and caspase-9 was achieved only through the feedback amplification loop. This feedback amplification loop also played a predominant role during programmed cell death of dorsal root ganglia neurons at mouse embryonic day 11.5.

Amino Acid Sequence↗

PubMed2000

Detection of caspase-9 activation in the cell death of the Bcl-x-deficient mouse embryo nervous system by cleavage sites-directed antisera.

Caspases, which play crucial roles during apoptosis, are activated from their inactive proforms in a sequential cascade of cleavage by other members of the caspase family. Caspase-9 is autoprocessed by the Apaf-1/cytochrome c pathway and acts at an early point in this cascade, whereas Bcl-xL, an antiapoptotic member of the Bcl-2 family, prevents activation of caspases in vitro. Little is known, however, about the relation between caspase-9 and Bcl-xL during development of the mammalian nervous system. We used antisera against two cleavage sites in mouse caspase-9 that recognize only the activated form of mouse caspase-9, and we examined immunohistochemically the activation of mouse caspase-9 in the nervous system of Bcl-x-deficient mouse embryos. Mouse caspase-9 is processed at both D(353) and D(368), but it is processed preferentially at D(368) during apoptosis of cultured cells induced by various stimuli and in the nervous system of Bcl-x-deficient mouse embryos. We show that Bcl-xL protects against caspase-9- and/or caspase-3-dependent apoptosis in the caudal portion of the ventral hindbrain, anterior horn cells, and dorsal root ganglia neurons of the normal mouse embryos and against caspase-9/caspase-3-independent apoptosis in the dorsal region of the nervous system including the dorsal spinal cord. Furthermore, we demonstrate that Bcl-xL blocks cytochrome c release from mitochondria, causing activation of caspase-9 in anterior horn cells and dorsal root ganglia neurons in mouse embryos at embryonic day 11.5.

Animals↗

PubMed1990

[Iris nevus (Cogan-Reese) syndrome--clinicopathological correlations].

Clinicopathological correlations of iris nevus (Cogan-Reese) syndrome were studied by light and electron microscopy, using tissues obtained surgically by trabeculectomy and peripheral iridectomy. The patient was a 52-year-old female, who had a typical appearance of the disease with nodular iris nevi, distorted pupil, ectropion uveae, peripheral anterior synechia, and intractable glaucoma. The histopathological studies of the specimen revealed abnormal corneal endothelialization and basal lamina formation continuously covering the peripheral cornea, trabecular meshwork, and anterior iris surface. Lymphocyte infiltration was found in the layer of the endothelialization and in the anterior iris stroma. The nodular iris nevi were found to consist of mainly integration of degenerated iris melanocytes and clump cells of Koganei. Neovascularization associated with infiltration of lymphocytes and macrophages was also observed in the trabecular meshwork. The present study suggests that the disease might occur by chronic inflammation primarily as corneal endothelitis and iritis.

Endothelium, Corneal↗