Adriamycin enhances proteasome-mediated generation of the proapoptotic processed form of MAGE-A4 in hepatoma cells.

BACKGROUND: Melanoma antigen (MAGE)-A4 is processed to generate a C-terminal fragment with proapoptotic activity. Here we demonstrate that Adriamycin promotes generation of the processed MAGE-A4 by activating the proteasome. The proteasome is known to prevent accumulation of toxic proteins to maintain cellular homeostasis. METHODS AND RESULTS: Treatment of hepatoma cells expressing MAGE-A4 with a sublethal dose of Adriamycin increased the MAGE-A4 processing and sensitized the cells to Adriamycin-induced apoptosis. The processing of MAGE-A4 was inhibited by the proteasome inhibitors MG115, MG132, lactacystin and epoxamicin. MAGE-A4 was coimmunoprecipitated with the S6 proteasomal ATPase, and present in the fractions containing the proteasome during glycerol gradient centrifugation. Consistent with the notion that the proteasome cleaves MAGE-A4, the 26S proteasome, ubiquitin, and cell lysates were necessary for efficient in vitrocleavage of MAGE-A4. CONCLUSIONS: The present study suggests that a low dose of Adriamycin increases the proteasome activity, which either maintains cellular homeostasis or leads to apoptosis depending, at least under the present conditions, on the expression of MAGE-A4.

Passive erbium-doped fiber seed photon generator for high-power Er(3+)-doped fiber fluorescent sources with an 80-nm bandwidth.

A novel structure that converts wasted backward amplified spontaneous emission (ASE) to seed photons for the amplifier stage is suggested for a high-power erbium-doped fiber (EDF) broadband source. A considerable increase in output power and bandwidth extension was achieved by placement of a segment of passive EDF in front of the amplifier stage, thus recycling backward ASE as the secondary pumping source for the passive EDF seed photon generator. Experimental results showed a dramatic increase in output ASE power of more than 10 dB for most radiation bands from 1540 to 1620 nm with the simple addition of an unpumped EDF segment to the ordinary fluorescence-source structure.