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DYSREGULATION OF THE (IMMUNO)PROTEASOME PATHWAY IN MCD
units under both unstimulated and stimulated conditions (Fig. 7A, B). β5 and β5i expres- sion was reduced by rapamycin in the presence of IL-1β (Fig. 7C, D). Immunocytochemical analysis of these FCD cells confirmed the negative modulation of proteasome subunits by rapamycin (Fig. 8).
Discussion
The present study reports in detail the expression pattern and cellular localization of the constitutive and immunoproteasome subunits in FCD II and TSC cortical tubers and mMCD. The cell-specific distribution of proteasome subunits in relation with the epilep- togenicity of these developmental lesions as well as their regulation in human astrocytes is discussed in the following paragraphs.
Proteasome subunits expression in malformations of cortical development: prominent expression in FCD II and TSC
Our data show prominent expression of both constitutive and immunoproteasome sub- units in MCD, such as FCD and TSC, associated with the mTOR pathway. In all the FCD II and TSC specimens examined the IR for β1, β1, β5 and β5i was increased within the
Figure 5 Effects of IL-1β and LPS stimulation on immunoproteasome subunit expression in cell culture. Quantitative real-time PCR of proteasome expression in human fetal astrocytes after 24 hours exposure to IL-1β (10 ng/ml) or LPS (100 ng/ml). A-B, D-E: stimulation with IL-1β or LPS increased expression of the β1i (B) and the β5i (E) subunits compared to control, but not of the constitutive β1 (A) and β5 (D) subunits. C and F: stimulation with either IL-1β or LPS increased the β1i/ β1 (C) and the β5i/ β5 (F) ratios. Data are expressed relative to the levels observed in untreated cells and are mean ± SEM (n=5). **p < 0.01, ***p < 0.001 compared to control, Mann Whitney U test.
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