Accumulation of protein aggregates induces autolytic programmed cell death in hybrid tobacco cells expressing hybrid lethality.

Hybrid cells of Nicotiana suaveolens x N. tabacum grow normally at 36 °C, but immediately express lethality due to probable autoimmune response when transferred from 36 to 28 °C. Our recent study showed that the temperature-sensitive lethality of these hybrid cells occurs through autolytic programmed cell death (PCD). However, what happens in hybrid cells following the induction of autoimmune response to autolytic PCD is unclear. We hypothesized that accumulation of protein aggregates in hybrid cells induces autolytic PCD and examined detergent-insoluble protein (protein aggregates) isolated from hybrid cells expressing lethality. The amount of insoluble proteins increased in hybrid cells. Sodium 4-phenylbutyrate, a chemical chaperone, inhibited both the accumulation of insoluble proteins and irreversible progression of cell death. In contrast, E-64, a cysteine protease inhibitor, accelerated both the accumulation of insoluble proteins and cell death. Moreover, proteome analysis revealed that proteasome-component proteins were accumulated specifically in cells treated with E-64, and proteasome activity of hybrid cells decreased after induction of lethality. These findings demonstrate that accumulation of protein aggregates, including proteasome subunits, eventually cause autolytic PCD in hybrid cells. This suggests a novel process inducing plant PCD by loss of protein homeostasis and provides clues to future approaches for elucidating the whole process.

Aromatase inhibitor use during ovarian stimulation suppresses growth of uterine endometrial cancer in xenograft mouse model.

STUDY QUESTION: Could aromatase inhibitors (AI) be used to reduce risks of uterine endometrial cancer growth or recurrence during ovarian stimulation? SUMMARY ANSWER: In a xenograft mouse model of endometrial cancer, concomitant AI administration suppressed the growth of endometrial cancer during ovarian stimulation. WHAT IS KNOWN ALREADY: Recurrence and mortality rates of estrogen receptor-positive early breast cancer are reduced by long-term AI administration. Concomitant AI use for ovarian stimulation in patients with breast cancer is recommended for reducing estrogen-related potential risks. However, the efficacy of concomitant AI use for estrogen receptor-positive endometrial cancer have not been demonstrated conclusively by clinical or experimental animal studies. STUDY DESIGN, SIZE, DURATION: Forty nude mice xenografted with uterine endometrial cancer cells were allocated to four groups. Group 1: no ovarian stimulation (control). Group 2: ovarian stimulation. Group 3: AI administration + ovarian stimulation. Group 4: ovariectomy and ovarian stimulation. Tumor growth was evaluated during the 6-week treatment period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ishikawa 3-H-12 uterine endometrial cancer cells (estrogen and progesterone receptors-positive) were transplanted into 6-week-old BALB/cSlc-nu/nu nude mice, followed by interventions 2 weeks later. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to ovarian stimulation alone (Group 2), significant suppressions of tumor growth were observed in other three groups (Groups 1, 3 and 4, all at P < 0.05) and correlated with estrogen levels. AI administration had no apparent impact on embryo development. LIMITATIONS, REASONS FOR CAUTION: In this study, we examined the growth of endometrial cancer tumors using one endometrial cancer cell line. Clinical endometrial cancer or hyperplasia cells can have diverse origins and AI may not be effective against other cancer cell types. WIDER IMPLICATIONS OF THE FINDINGS: Concomitant AI use may provide a chance for safer childbirth by for patients with endometrial cancer or hyperplasia. STUDY FUNDING/CONPETING INTEREST(S): This study was supported by the Graduate Student Aid from the St. Marianna University School of Medicine. The authors declare no competing interests.

RNA-binding proteins associated with desiccation during seed development in rice.

Long-lived mRNAs stored in mature seeds can remain active for long periods even if seeds undergo severe desiccation. They are then translated at the initiation of germination. To clarify the mechanism for stabilization of long-lived mRNAs during seed desiccation, fluctuations in RNA-binding protein (RBP) profiles that occur during seed formation in rice were analyzed. Proteomic analysis revealed that glycine-rich RBP 1A (GRP1A) is a highly abundant RBP in mature rice seeds. In addition, real-time RT-PCR analysis showed that putative RBP RZ-1A (RZ-1A) is seed specific. Moreover, transcripts of these two RBPs were clearly up-regulated during desiccation in rice seeds. The features of these two RBPs resemble those of late embryogenesis abundant proteins that function as molecular chaperones in dry seeds. Therefore, GRP1A and RZ-1A may have important roles in the stability of long-lived mRNAs in rice seeds.