Suchergebnisse

"Hippo signaling has been recognized as a newly identified tumor suppressor signaling pathway that can regulate cellular processes including regeneration, cell death, differentiation, and development. Its dysregulation through overexpression of YAP (Yes-associated protein) and TAZ (PDZ-binding motif) as two main oncogenic factors of the Hippo pathway has a crucial role in several cancers. Because of the limited prognosis and therapeutic targets, further understanding of molecular pathways involved in tumorigenesis is one of the interesting issues in studies. Here, we demonstrated that some viruses, through dysregulation of the Hippo signaling pathway can be implicated in transformation, metastasis, and chemotherapeutic drug resistance in virus-related cancer and also help processes involved in the pathogenesis of viral infection such as persistence "

Mechanical force is known to modulate the activity of the Jun N-terminal kinase (JNK) signaling cascade. However, the effect of mechanical stresses on JNK signaling activation has previously only been analyzed by in vitro detection methods. It still remains unknown how living cells activate the JNK signaling cascade in response to mechanical stress and what its functions are in stretched cells. We assessed in real-time the activity of the JNK pathway in Drosophila cells by Fluorescence Lifetime Imaging Microscopy (FLIM), using an intramolecular phosphorylation-dependent dJun-FRET (Fluorescence Resonance Energy Transfer) biosensor. We found that quantitative FRET-FLIM analysis and confocal microscopy revealed sustained dJun-FRET biosensor activation and stable morphology changes in response to mechanical stretch for Drosophila S2R+ cells. Further, these cells plated on different substrates showed distinct levels of JNK activity that associate with differences in cell morphology, integrin expression and focal adhesion organization. These data imply that alterations in the cytoskeleton and matrix attachments may act as regulators of JNK signaling, and that JNK activity might feed back to modulate the cytoskeleton and cell adhesion. We found that this dynamic system is highly plastic; at rest, integrins at focal adhesions and talin are key factors suppressing JNK activity, while multidirectional static stretch leads to integrin-dependent, and probably talin-independent, Jun sensor activation. Further, our data suggest that JNK activity has to coordinate with other signaling elements for the regulation of the cytoskeleton and cell shape remodeling associated with stretch. ; AMP held a Spanish FPU PhD studentship and CT was supported by the Marie Curie Research Training Network IMMUNANOMAP (MRTNCT-2006-035946). Research in the EMB laboratory is funded by grants of the Spanish Ministry of Science (DGI and Consolider) and the European Union. Research in the VS laboratory is supported by "Stichting voor Fundamenteel Onderzoek der Materie", the "Nederlandse Organisatie voor Wetenschappelijk Onderzoek", and the European Union. ; Peer reviewed

AbstractDysfunction at various levels of spermatogenesis (SD) is one of the important causes of infertility in men of reproductive age and requires advanced treatment strategies. Increasing evidence suggests that the therapeutic effects of echinacoside (ECH) mainly depend on their capacity to inhibit cell death. This study aimed to explore the therapeutic potential of ECH in SD rat models. Treatment with ECH reverted the morphological changes observed in testes with spermatogenesis dysfunction. It improved total sperm number, decreased the sperm deformity rate, and increased the sperm forward motility rate. The level of glutathione (GSH) was significantly higher in ECH-treated mice, whereas the lactate dehydrogenase (LDH) and SOD activities were improved compared with those in the spermatogenesis dysfunction model. Moreover, the increased expression of p38 and JNK was partially reversed by ECH. The number of normal TM3 cells increased gradually in an Echinacea dosage-dependent manner, suggesting that ECH promoted the proliferation of TM3 cells. In addition, treatment with ECH partially reversed the increased expression of p38 and JNK in TM3 cells. ECH protects against oxidative stress damage by activating antioxidant enzymes and MAPK signaling-related factors (p38 and JNK). It suggested that treatment with ECH alleviated spermatogenetic dysfunction of testes in male mice and it could be a promising strategy for patients suffering severe SD.