Differentiation of neuronal cells has been shown to accelerate stress-induced cell death, but the underlying mechanisms are not completely understood. Here, we find that early and sustained increase in cytosolic ([Ca2+]c) and mitochondrial Ca2+ levels ([Ca2+]m) is essential for the increased sensitivity to staurosporine-induced cell death following neuronal differentiation in PC12 cells. Consistently, pretreatment of differentiated PC12 cells with the intracellular Ca2+-chelator EGTA-AM diminished staurosporine-induced PARP cleavage and cell death. Furthermore, Ca2+ overload and enhanced vulnerability to staurosporine in differentiated cells were prevented by Bcl-XL overexpression. Our data reveal a new regulatory role for differentiation-dependent alteration of Ca2+ signaling in cell death in response to staurosporine.
Animals ; Calcium/*metabolism ; Caspase 3/metabolism ; Cell Differentiation/*physiology ; DNA Fragmentation ; Mitochondria/metabolism ; *Neurons/cytology/drug effects/physiology ; *PC12 Cells/cytology/drug effects/physiology ; Rats ; Staurosporine/*pharmacology ; bcl-X Protein/metabolism

TGF-beta1 is well known to induce Ig germ-line alpha (GLalpha) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-beta signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFbeta1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFbeta1-induced GLalpha promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLalpha promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFbeta1-induced GLalpha expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLT(alpha), PST(alpha), and CT(alpha)) and TGFbeta1-induced IgA secretion, but not GLT(gamma3) and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFbeta1-induced IgA isotype expression.
Down-Regulation ; Immunoglobulin A ; Immunoglobulin Class Switching ; Immunoglobulin G ; Ligases ; Recombination, Genetic ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Ubiquitin

PURPOSE: We wanted to evaluate an acceptable compression rate of JPEG2000 for long term archiving of CT and MR images in PACS. MATERIALS AND METHODS: Nine CT images and 9 MR images that had small or minimal lesions were randomly selected from the PACS at our institute. All the images are compressed with rates of 5:1, 10:1, 20:1, 40:1 and 80:1 by the JPEG2000 compression protocol. Pairs of original and compressed images were compared by 9 radiologists who were working independently. We designed a JPEG2000 viewing program for comparing two images on one monitor system for performing easy and quick evaluation. All the observers performed the comparison study twice on 5 mega pixel grey scale LCD monitors and 2 mega pixel color LCD monitors, rspectively. The PSNR (Peak Signal to Noise Ratio) values were calculated for making quantitative comparisons. RESULTS: On MR and CT, all the images with 5:1 compression images showed no difference from the original images by all 9 observers and only one observer could detect a image difference on one CT image for 10:1 compression on only the 5 mega pixel monitor. For the 20:1 compression rate, clinically significant image deterioration was found in 50% of the images on the 5M pixel monitor study, and in 30% of the images on the 2M pixel monitor. PSNR values larger than 44 dB were calculated for all the compressed images. CONCLUSION: The clinically acceptable image compression rate for long term archiving by the JPEG2000 compression protocol is 10:1 for MR and CT, and if this is applied to PACS, it would reduce the cost and responsibility of the system.
Data Compression ; Noise