The p34SEI-1 protein exerts oncogenic effects via regulation of the cell cycle, which occurs through a direct interaction with cyclin-dependent kinase 4. Such regulation can increase the survival of various types of tumor cells. Here, we show that the antiapoptotic function of p34 SEI-1 increases tumor cell survival by protecting the X-linked inhibitor of apoptosis protein (XIAP) from degradation. Our findings show that p34 inhibits apoptosis. This antiapoptotic effect was eliminated by the suppression of p34 SEI-1 expression. We also determined that direct binding of p34 SEI-1 to the BIR2 domain prevents ubiquitination of XIAP. Interestingly, p34SEI-1 expression is absent or weak in normal tissues but is strongly expressed in tissues obtained from patients with breast cancer. Furthermore, the expression levels of p34 SEI-1 and XIAP seem to be coordinated in human breast cancer cell lines and tumor tissues. Thus, our findings reveal that p34 SEI-1 uses a novel apoptosis-inhibiting mechanism to stabilize XIAP. [Cancer Res 2009;69(3):741-6]
Rheumatoid arthritis (RA) synoviocytes are resistant to apoptosis and exhibit a transformed phenotype, which might be caused by chronic exposure to genotoxic stimuli including reactive oxygen species and growth factors. In this study, we investigated the role of vascular endothelial growth factor165 (VEGF165), a potent angiogenic factor, and its receptor in the apoptosis of synoviocytes. We demonstrated here that neuropilin-1, rather than fms-like tyrosine kinase-1 and kinase insert domain-containing receptor, is the major VEGF165 receptor in the fibroblast-like synoviocytes. Neuropilin-1 was highly expressed in the lining layer, infiltrating leukocytes, and endothelial cells of rheumatoid synovium. The production of VEGF165, a ligand for neuropilin, was significantly higher in the RA synoviocytes than in the osteoarthritis synoviocytes. The ligation of recombinant VEGF165 to its receptor prevented the apoptosis of synoviocytes induced by serum starvation or sodium nitroprusside (SNP). VEGF165 rapidly triggered phospho-Akt and phospho-ERK activity and then induced Bcl-2 expression in the rheumatoid synoviocytes. The Akt or ERK inhibitor cancelled the protective effect of VEGF165 on SNP-induced synoviocyte apoptosis. Moreover, VEGF165 blocks SNP-induced Bcl-2 down-regulation as well as SNP-induced Bax translocation from the cytosol to the mitochondria. The down-regulation of the neuropilin-1 transcripts by short interfering RNA caused spontaneous synoviocyte apoptosis, which was associated with both the decrease in Bcl-2 expression and the increase in Bax translocation to mitochondria. Collectively, our data suggest that the interaction of VEGF165 with neuropilin-1 is crucial to the survival of rheumatoid synoviocytes and provide important implications for the abnormal growth of synoviocytes and therapeutic intervention in RA.
Abstract. Although ascorbate (Vitamin C) has been shown to inhibit cell growth and induce cell death in variety of cancer cells, results reported in other studies are inconsistent with this conclusion. It was previously reported that ascorbate induces apoptosis in human breast cancer cells. However, the molecular mechanism for this is not clear. In this study, we demonstrate that ascorbate induces cell death through the apoptosis-inducing factor (AIF) in the human breast cancer cell lines, SK-BR3 and Hs578T, but not in a normal breast cell line, Hs578. Ascorbate treatment caused the nuclear translocation of AIF, which is retained in the mitochondria in healthy cells, but caspase cleavage is not induced. Moreover, MG132, an inhibitor of AIF release from mitochondria, blocked the induction of cell death. Furthermore, cells that had been treated with human AIF-specific siRNA resisted cell death induced by ascorbate, implying that the translocation of AIF from mitochondria to the nucleus is responsible for ascorbate-mediated cell death. Therefore, these results suggest that ascorbate activates a caspase-independent and AIFmediated cell death pathway in human breast cancer cells, SK-BR3, and Hs578T.
Low energy proton-proton scattering is studied in pionless effective field theory. Employing the dimensional regularization and MS and power divergence subtraction schemes for loop calculation, we calculate the scattering amplitude in 1 S 0 channel up to nextto-next-to leading order and fix low-energy constants that appear in the amplitude by effective range parameters. We study regularization scheme and scale dependence in separation of Coulomb interaction from the scattering length and effective range for the S-wave proton-proton scattering.PACS(s): 11.10.Gh, 13.75.Cs.1 mailto:sando@color.skku.ac.kr 1 IntroductionEffective field theories (EFTs), which provide us a systematic perturbative scheme and a model-independent calculation method, have become a popular method to study hadronic reactions with and without external probes at low and intermediate energies.(See, e.g., Refs. [1, 2, 3, 4, 5] for reviews.) At very low energies, the Coulomb interaction becomes essential for the study of reactions involving charged particles. The first consideration of the Coulomb interaction in a pionless EFT was done by Kong and Ravndal (KR) for low energy S-wave proton-proton (pp) scattering [6,7]. They calculated the pp scattering amplitude up to next-to leading order (NLO). For loop calculations, they employed dimensional regularization with minimum subtraction (MS) scheme and so called power divergence subtraction (PDS) scheme suggested by Kaplan, Savage and Wise [8,9]. Then KR estimated a scattering length a(µ) for the pp scattering after separating off the Coulomb correction where µ is the scale for dimensional regularization. The leading order (LO) result of a(µ) was almost infinite at µ = m π where m π is the pion mass [6]. In addition, the LO a(µ) was highly dependent on the value of µ. Including the NLO correction, they obtained a(µ = m π ) = −29.9 fm [7] which is comparable to the value of the scattering length a np in the np channel, a np = −23.748 ± 0.009 fm 2 . The value of a(µ) deduced after separating the Coulomb and strong interactions is particularly important in the study of isospin breaking effects in S-wave NN interaction [11,12]. The accurate value of a np is well known as quoted above, while the values of the scattering length in the nn channel (a nn ) and in the pp channel (a pp ) still have considerable uncertainties.There exists no direct nn scattering experiment because of the lack of free neutron target. The values of a nn have been deduced from the experimental data of π − d → nnγ and nd → nnp reactions. Recent publications suggest a nn = −18.50 ± 0.05(stat.) ± 0.44(syst.) ± 0.30(th.) fm from the π − d → nnγ process [13] and a nn = −18.7 ± 0.6 fm [14], −16.06 ± 0.35 fm [15] and −16.5 ± 0.9 fm [16] from the nd → nnp process. As seen, the values of a nn have significant errors compared to that of a np , and the center values do not seem to converge yet.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.