Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways

The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Analysis of the volatile compounds of Brazilian chilli peppers (Capsicum spp.) at two stages of maturity by solid phase micro-extraction and gas chromatography-mass spectrometry

The volatile fractions of three varieties of chilli peppers at two stages of maturity were characterised using headspace solid phase micro-extraction (HS-SPME), gas chromatography (GC-FID) and mass spectrometry (GC-MS). A total of 83 compounds, mostly esters and alcohols, were identified in the malagueta chilli pepper (Capsicum frutescens), 49 compounds, mostly monoterpenes and aldehydes, were identified in the dedo-de-moca chilli pepper (Capsicum baccatum var. pendulum) and 77 compounds, mostly esters and sesquiterpenes, were identified in the murupi chilli pepper (Capsicum chinense). The peak areas of the compounds were smaller in the more mature samples. The samples from C. baccatum var. pendulum exhibited the greatest decrease; most of the compounds were not detected in the more mature samples. (C) 2012 Elsevier Ltd. All rights reserved.4819810