Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae

Signal transduction pathways control cellular responses to extrinsic and intrinsic signals. The yeast HOG (High Osmolarity Glycerol) response pathway mediates cellular adaptation to hyperosmotic stress. Pathway architecture as well as the flow of signal have been studied to a very high degree of detail. Recently, the yeast HOG pathway has become a popular model to analyse systems level properties of signal transduction. Those studies addressed, using experimentation and modelling, the role of basal signalling, robustness against perturbation, as well as adaptation and feedback control. These recent findings provide exciting insight into the higher control levels of signalling through this MAPK system of potential general importance.     

Biosynthesis of (−)-ent-kaurenoic acid in Smallanthus sonchifolius and its effect against microbial biofilms

The biosynthetic pathway of (–)-ent-kaurenoic acid (1) was investigated by incorporation of 1-d-¹³C-glucose in Smallanthus sonchifolius (Asteraceae) plantlets. The ¹³C-enrichment pattern indicated that methylerythritol-4-phosphate (MEP) pathway is the biosynthetic pathway involved in diterpenoid biosynthesis. Our studies in S. sonchifolius reinforce that the biosynthesis of different classes of terpenes should not be compartmentalized into cytosol and plastids. Additionally, (–)-ent-kaurenoic acid showed antimicrobial activity against Staphylococcus aureus biofilm.     

Oxypetalum banksii subsp. banksii: a taxon of Asclepiadaceae with an extragynoecial compitum

 The floral morphology of seven Oxypetalum species and, in particular, the spatial relationship between the five stigmatic chambers and two separate ovaries of their flowers with respect to transmission of the pollen tube are studied. In all species, except O. banksii subsp. banksii, floral morphology is similar to that in other Asclepiadeae, and the flowers pollinated with one pollinium develop only one follicle, which means compitum absence. In O. banksii subsp. banksii flowers, the secretory interstaminal tissue lines the inner walls of the stigmatic chambers as in the other species studied, but it also reaches the upper part of the inner surface of the filament tube, where it surrounds the styles, an unprecedented feature for Asclepiadaceae. This tissue secretes nectar and mucilage; the latter acts as transmitting medium for the growth of pollen tubes from pollinia inserted and hydrated in stigmatic chambers (“hyperstigmas”). Mucilage also functions as an extragynoecial compitum: in flowers pollinated with one pollinium both carpels develop into a follicle. Received August 28, 2001; accepted April 9, 2002 Published online: October 14, 2002 Addresses of the authors: Milene Faria Vieira (e-mail: mfvieira@mail.ufv.br), Departamento de Biologia Vegetal, Universidade Federal de Vi?osa, 36571-000, Vi?osa, Minas Gerais, Brazil. George John Shepherd, Departamento de Botanica, Instituto de Biologia, Universidade Estadual de Campinas, C.P. 6109, 13083-970, Campinas, S?o Paulo, Brazil.     

Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+ Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway

Cervical cancer (CCa) is the second most frequent carcinoma in females and human papilloma virus (HPV) oncoproteins are regarded as one of the critical etiological agent. Despite recent advances in screening and management of CCa, still it remains the deadliest carcinoma as advanced and metastatic stages are mostly incurable. This urges for the development of newer therapeutic interventions. The current was aimed to investigate the antiproliferative and apoptotic potential of glycyrrhizin (Gly) against HPV16⁺ CaSki CCa cells. Our findings substantiated that Gly exerted antiproliferative effects on the CaSki cells by obstructing their proliferation rate. Gly substantially enhanced apoptosis in Caski cells in a dose-dependent manner via augmenting the generation of ROS, DNA fragmentation and disruption of the mitochondrial membrane potential. Gly mediated apoptosis in CaSki cells was found to be due to activation of caspase-8 and capsase-9 along with the modulation of pro-and anti-apoptotic gene expression. Moreover, Gly halts the progression of CaSki cells at G₀/G₁ phase which was found to be due to reduced expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) along with the enhanced expression of CDK inhibitor p21^Cip1. Further, Gly downregulates the expression of HPV oncoproteins (E6 & E7) along with the inhibition of Notch signaling pathway. Taken together, Gly represents as a potential therapeutic modality for CCa which could rapidly be translated for clinical studies.     

The Neuroprotective Adenosine-Activated Signal Transduction Pathway Involves Activation of Phospholipase C

We have demonstrated before that exposure of neuronal cultures to poisoning by iodoacetic acid (IAA) followed by “reperfusion” (IAA-R insult), results in severe cytotoxicity, which could be markedly attenuated by prior activation of the adenosine A₁ receptors. We also have demonstrated that adenosine activates a signal transduction pathway (STP), which involves activation of PKCε and opening of K_ATP channels. Here, we provide proof for the involvement also of phospholipase C (PLC) in the neuronal protective adenosine-activated STP. R-PIA, a specific A₁ adenosine receptor agonist, was found to enhance neuronal PLC activity and protect against the IAA-R insult. The PLC inhibitor U73122, abrogated both R-PIA-induced effects. These results demonstrate that activation of PLC is a vital step in the neuronal protective adenosine-induced STP.