| 1. |
- Brehmer, M, et al.
(författare)
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Heat-induced apoptosis in human prostatic stromal cells
- 2000
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 85:4, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine whether heat, used in transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia and which causes necrotic lesions within the adenoma, induces apoptosis in benign human prostatic stromal cells. Materials and methods. Prostatic stromal cells were cultured from benign human prostatic tissue. The origin of the cells was identified by immunohistochemical staining and transmission electron microscopy. Cell cultures were exposed to moderate hyperthermia (47░C) for 1 h and any apoptosis detected by light microscopy, transmission electron microscopy and the measurement of induced caspase-3-like activity. Results. The cultures contained a mixed population of smooth muscle cells and myofibroblasts. Twenty-four hours after heat exposure, 76% of the cells were apoptotic and the caspase activity had increased, whereas only 14% of the cells were necrotic. Conclusion. Moderate hyperthermia induces apoptosis in cultured human prostatic stromal cells.
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| 3. |
- Kågedal, Katarina, 1970-, et al.
(författare)
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Sphingosine-induced apoptosis is dependent on lysosomal proteases
- 2001
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 359:2, s. 335-343
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Tidskriftsartikel (refereegranskat)abstract
- We propose a new mechanism for sphingosine-induced apoptosis, involving relocation of lysosomal hydrolases to the cytosol. Owing to its lysosomotropic properties, sphingosine, which is also a detergent, especially when protonated, accumulates by proton trapping within the acidic vacuolar apparatus, where most of its action as a detergent would be exerted. When sphingosine was added in low-to-moderate concentrations to Jurkat and J774 cells, partial lysosomal rupture occurred dose-dependently, starting within a few minutes. This phenomenon preceded caspase activation, as well as changes of mitochondrial membrane potential. High sphingosine doses rapidly caused extensive lysosomal rupture and ensuing necrosis, without antecedent apoptosis or caspase activation. The sphingosine effect was prevented by pre-treatment with another, non-toxic, lysosomotropic base, ammonium chloride, at 10mM. The lysosomal protease inhibitors, pepstatin A and epoxysuccinyl-L-leucylamido-3-methyl-butane ethyl ester ('E-64d'), inhibited markedly sphingosine-induced caspase activity to almost the same degree as the general caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone ('Z-VAD-FMK'), although they did not by themselves inhibit caspases. We conclude that cathepsin D and one or more cysteine proteases, such as cathepsins B or L, are important mediators of sphingosine-induced apoptosis, working upstream of the caspase cascade and mitochondrial membrane-potential changes.
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