期刊
BIOCHEMICAL JOURNAL
卷 381, 期 -, 页码 609-618出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20031857
关键词
apoptosis; phosphatidylserine (PtdSer); phosphatidylserine synthase I (PSS I); PSSII; scramblase; ultraviolet light
Externalization of PtdSer (phosphatidylserine) is an important event in signalling removal of apoptotic cells. In contrast with previous work [Yu, Byers, Ridgway, McMaster and Cook (2000) Biochim. Biophys. Acta 1487,296-308] with U937 cells showing that specific stimulation of PtdSer biosynthesis during apoptosis was caspase dependent, PtdSer biosynthesis in CHO (Chinese-hamster ovary)-K1 increased 2.5-fold during UV-induced apoptosis but was not reversed by a caspase inhibitor, Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone). Also, in CHO-K1 cells. stimulation of synthesis was less specific for PtdSer as similar levels of stimulation were observed for sphingomyelin biosynthesis. Involvement of PtdSer synthase isoforms was tested in CHO-K1 cells overexpressing PSS I (PtdSer synthase 1) and PSS II. Both types of transformed cells showed resistance to UV-induced apoptosis based on the decreased levels of caspase 3 activation and morphology changes; externalization of PtdSer was reduced with UV treatment even though expression of endogenous scramblase increased slightly. Serine-labelling experiments showed that PSS I- or PSS II-expressing cells had higher basal levels of PtdSer biosynthesis compared with vector control cells. When cells were exposed to UV light to induce apoptosis, PtdSer biosynthesis was further stimulated 1.5 and 2-fold in PSS I- and PSS II-expressing cells respectively compared with UV-treated vector cells. Caspase activation was not required, as Z-VAD-FMK did not change PtdSer synthesis. Although enhanced PtdSer synthesis was supposed to facilitate apoptosis, cells overexpressing PSS I and II were actually resistant to UV-induced apoptosis. Whereas enhanced PtdSer synthesis was associated with apoptosis, potential anti-apoptotic effects were observed when excess activity of these synthetic enzymes was present. This suggests a tightly regulated role for PtdSer synthesis and/or an important dependence on compartmentation of PSS enzymes in association with scramblase facilitated enrichment of this phospholipid at the cell surface.
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