摘要
Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exactbiological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavilydisputed, since data supporting both views have been reported in several independent studies. To clarify thisissue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the presentstudy, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis inthymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and afterinduction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering ofapoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptoticprocesses. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expressionwas restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolyticcleavage site and is therefore predicted to encode a monomeric protein. The biological function undernormal circumstances, however, will need further investigations for clarification. While apoptosis could notmodulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted inup-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control ofcell activation-mediated rather than apoptosis- induced signals.
Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exact biological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavily disputed, since data supporting both views have been reported in several independent studies. To clarify this issue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the present study, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis in thymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and after induction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering of apoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptotic processes. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expression was restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolytic cleavage site and is therefore predicted to encode a monomeric protein. The biological function under normal circumstances, however, will need further investigations for clarification. While apoptosis could not modulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted in up-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control of cell activation-mediated rather than apoptosis- induced signals.
基金
This work was supported by grant No. R05-2001-000-00464-0 from the Basic Research Program of the Korea Science and Engineering Foundation. The authors are very thankful to M.L. Cowan for corrections and suggestions to the text.
