The Anticancer Plant Triterpenoid, Avicin D, Regulates Glucocorticoid Receptor Signaling: Implications for Cellular Metabolism

Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from “ancient hopanoids,” avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use

Vasilescu-Martinelli formula for operators in Banach spaces

We prove a formula for the Taylor functional calculus for functions analytic in a neighbourhood of the splitting spectrum of an n-tuple of commuting Banach space operators. This generalizes the formula of Vasilescu for Hilbert space operators and is closely related to a recent result of D. W. Albrecht

On the axiomatic theory of spectrum

There are a number of spectra studied in the literature which do not fit into the axiomatic theory of Żelazko. This paper is an attempt to give an axiomatic theory for these spectra, which, apart from the usual types of spectra, like one-sided, approximate point or essential spectra, include also the local spectra, the Browder spectrum and various versions of the Apostol spectrum (studied under various names, e.g. regular, semiregular or essentially semiregular)

The index for Fredholm elements in a Banach algebra via a trace II

summary:We show that the index defined via a trace for Fredholm elements in a Banach algebra has the property that an index zero Fredholm element can be decomposed as the sum of an invertible element and an element in the socle. We identify the set of index zero Fredholm elements as an upper semiregularity with the Jacobson property. The Weyl spectrum is then characterized in terms of the index