Proteomics analysis of meclofenamic acid-treated small cell lung carcinoma cells revealed changes in cellular energy metabolism for cancer cell survival

Small cell lung carcinoma (SCLC) is a highly aggressive cancer with low survival rate. Although initial response to chemotherapy in SCLC patients is well-rated, the treatments applied after the disease relapses are not successful. Drug resistance is accepted to be one of the main reasons for this failure. Therefore, there is an urgent need for new treatment strategies for SCLC. Meclofenamic acid, a nonsteroidal anti-inflammatory drug, has been shown to have anticancer effects on various types of cancers via different mechanisms. The aim of this study was to investigate the alterations that meclofenamic acid caused on a SCLC cell line, DMS114 using the tools of proteomics namely two-dimensional gel electrophoresis coupled to MALDI-TOF/TOF and nHPLC coupled to LC-MS/MS. Among the proteins identified by both methods, those showing significantly altered expression levels were evaluated using bioinformatics databases, PANTHER and STRING. The key altered metabolism upon meclofenamic acid treatment appeared to the cellular energy metabolism. Glycolysis was suppressed, whereas mitochondrial activity and oxidative phosphorylation were boosted. The cells underwent metabolic reprogramming to adapt into their new environment for survival. Metabolic reprogramming is known to cause drug resistance in several cancer types including SCLC. The identified differentially regulated proteins in here associated with energy metabolism hold value as the potential targets to overcome drug resistance in SCLC treatment.     

Metabolic syndrome and urologic diseases

Metabolic syndrome (MetS) is a complex entity consisting of multiple interrelated factors including insulin resistance, central adiposity, dyslipidemia, endothelial dysfunction and atherosclerotic disease, low-grade inflammation, and in males, low testosterone levels. MetS has been linked to a number of urologic diseases including nephrolithiasis, benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, male infertility, female incontinence, and prostate cancer. This article reviews the relationships between MetS and these entities. Urologists need to be cognizant of the impact that MetS has on urologic diseases as well as on overall patient health.     

Helminths of roe deer (Capreolus capreolus) in the Middle Black Sea Region of Turkey

Fifteen roe deer were examined at necropsy from Northern Turkey in the period 2006-2010 for the helminth infections. Totally 6470 helminth specimens were collected and identified by morphological criteria. Twenty-five helminth species were identified (1 of the Class Trematoda, 1 of Cestoda and 23 of Nematoda). Dicrocoelium dendriticum (Prevalence 20%) was found in liver. Cysticercus tenuicollis (6.6%) was found in mesentery. Haemonchus contortus (53.3%), Ostertagia leptospicularis (73.3%), O. leptospicularis (minor morph: kolchida) (53.3%), Ostertagia ostertagi (26.6%), Spiculopteragia spiculoptera (66.6%), S. spiculoptera (minor morph: mathevossiani) (6.6%), Teladorsagia circumcincta (40.0%), T. circumcincta (minor morph: davtiani) (6.6%), T. circumcincta (minor morph: trifurcata) (6.6%), Trichostrongylus axei (66.6%) were found in abomasum. Trichostrongylus andreevi (6.6%), T. colubriformis (6.6%), T. longispicularis (26.6%), T. vitrinus (40.0%), T. capricola (6.6%), Cooperia oncophora (26.6%), C. punctata (6.6%), Nematodirus filicollis (66.6%), and Capillaria bovis (26.6%) were found in small intestine. Oesophagostomum venulosum (46.6%), Chabertia ovina (26.6%), and Trichuris ovis (13.3%) were found in large intestine. Dictyocaulus capreolus (6.6%) was found in lungs.     

Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2

The pancreatic β-cell surface protein Tmem27 is promotes the preservation of functional β-cell mass. It is a selective substrate of the protease Bace2, yet the intramolecular features of Tmem27 that regulate its processing by this sheddase have not been characterized. In particular, the importance of homodimerization, glycosylation, trafficking to the plasma membrane (PM), the existence of multiple cleavage sites, and the amino acid residues that govern these features are currently unknown. Using Tmem27 mutational analysis and multiple biochemical approaches, we here show that Tmem27 dimerization is a dynamic process mediated by its intracellular cysteine residue and that prevents Tmem27 cleavage, that extracellular asparagine glycosylation is essential for Tmem27 trafficking to the PM and its processing by Bace2, that the amount of Tmem27 at the PM is proportional to its total cell levels upon glucose stimulation and Bace2 inhibition, and that the double phenylalanine motif in the Tmem27 cleavage site is an intramolecular Bace2 inhibitor. These findings define structural properties of Tmem27 that affect the susceptibility to its protease Bace2 and have implications for the efficiency with which Tmem27 and other Bace2 substrates are cleaved in normal and disease states.