Accumulating evidence during the last decades revealed that androgen can exert membrane initiated actions that involve signaling via specific kinases and the modulation of significant cellular processes, important for prostate cancer cell growth and metastasis. Results of the present work clearly show that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. In fact, OXER1 expression parallels that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. Interestingly, testosterone antagonizes the effects of 5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and metastasis. These findings verify that membrane-acting androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between androgen and OXER1, which is an arachidonic acid metabolite receptor expressed in prostate cancer, provides a novel link between steroid and lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in prostate cancer.

No abstract

In this study, the athermal effects of water-filtered infrared A (wIRA)-irradiation (780-1400 nm) on human dermal fibroblasts were investigated. For this purpose, cells were exposed to wIRA-irradiation (178 mW cm(-2) for 1 h), while a sophisticated experimental setup prevented warming of the samples exceeding 0.1°C. The investigated parameters were the formation of reactive oxygen species (ROS), mitochondrial membrane potential and superoxide release, protein oxidation, proliferation rate, as well as intracellular Ca(2+) -release in single cells, most of them quantified via fluorescence microscopy and fluorimetric techniques. The existence of actual athermal wIRA-effects is still intensively discussed, since their detection requires a careful experimental setup and both efficient and powerful temperature regulation of the exposed samples. Here, we can definitively show that some of the supposed athermal wIRA-effects may be rather artifacts, since wIRA did not reveal any impact on the above mentioned parameters-as long as the temperature of the exposed cells was carefully maintained. Though, we were able to identify an athermal DNA-protective wIRA-effect, since the induced DNA damage (quantified via 8-Oxo-G-formation) was significantly decreased after a subsequent UVB-exposure. These results suggest that many of the supposed athermal wIRA-effects can be induced by pure warming of the samples, independent from any wIRA-irradiation.

No abstract

• ▶ human myocardium • ▶ adrenal steroids • ▶ mineralocorticoid receptor • ▶ stress hormones • ▶ corticosteroid binding globulin Expression of Corticosteroid-Binding Globulin CBG in the Human Heart nently elevated plasma cortisol levels are associated with higher morbidity and mortality and increased cardiovascular risk [ 7 ]. In an experimental setting with adrenal ectomized rats, administration of cortisol and dexamethasone increased infarct size [ 8 ]. In this light it remains unclear how systemic adrenal steroids aff ect the heart: The benefi cial eff ects of MR inhibitors may relate to a blockade of mineralocorticoids [ 9 ] ; however, the actions of glucocorticoids need to be reinvestigated in this context. Cardiac remodeling has been shown to occur even in MR-deficient mice [ 10 ]. So some of the GC eff ects on cardiomyocytes may involve mechanisms independent from nuclear MR. While a huge body of clinical and physiological literature exists in this fi eld, there are only few morphological studies in humans so far. Corticosteroid-binding globulin (CBG) is a heterodimeric glycoprotein [ 11 ] with high affi nities to GC mineralocorticoids (MC). CBG is primarily expressed in liver [ 12 ] , capable of binding more

No abstract

No abstract

No abstract