Mouse anti-Human S6 (pS235/pS236) monoclonal antibody, clone O8-659 [Alexa Fluor® 647]

Low-force exercise training with blood flow restriction (BFR) elicits muscle hypertrophy as seen typically after higher-force exercise. We investigated the effects of microvascular hypoxia [i.e., low microvascular O-2 partial pressures (Pm nu O-2)] during contractions on muscle hypertrophic signaling, growth response, and key muscle adaptations for increasing exercise capacity. Wistar rats were fitted with a cuff placed around the upper thigh and inflated to restrict limb blood flow. Low-force isometric contractions (30 Hz) were evoked via electrical stimulation of the tibialis anterior (TA) muscle. The Pm nu O-2 was determined by phosphorescence quenching. Rats underwent acute and chronic stimulation protocols. Whereas Pm nu O-2 decreased transiently with 30 Hz contractions, simultaneous BFR induced severe hypoxia, reducing Pm nu O-2 lower than present for maximal (100 Hz) contractions. Low-force electrical stimulation (EXER) induced muscle hypertrophy (6.2%, P < 0.01), whereas control group conditions or BFR alone did not. EXER+BFR also induced an increase in muscle mass (11.0%, P < 0.01) and, unique among conditions studied, significantly increased fiber cross-sectional area in the superficial TA (P < 0.05). Phosphorylation of ribosomal protein S6 was enhanced by EXER+ BFR, as were peroxisome proliferator-activated receptor gamma coactivator-lot and glucose transporter 4 protein levels. Fibronectin type III domain-containing protein 5, cytochrome c oxidase subunit 4, monocarboxylate transporter 1 (MCT1). and cluster of differentiation 147 increased with EXER alone. EXER+BFR significantly increased MCT1 expression more than EXER alone. These data demonstrate that microvascular hypoxia during contractions is not essential for hypertrophy. However, hypoxia induced via BFR may potentiate the muscle hypertrophic response (as evidenced by the increased superficial fiber cross-sectional area) with increased glucose transporter and mitochondrial biogenesis, which contributes to the pleiotropic effects of exercise training with BFR that culminate in an improved capacity for sustained exercise. NEW & NOTEWORTHY We investigated the effects of low microvascular O-2 partial pressures (Pm nu O-2) during contractions on muscle hypertrophic signaling and key elements in the muscle adaptation for increasing exercise capacity. Although demonstrating that muscle hypoxia is not obligatory for the hypertrophic response to low-force, electrically induced muscle contractions, the reduced Pm nu O-2 enhanced ribosomal protein S6 phosphorylation and potentiated the hypertrophic response. Furthermore, contractions with blood flow restriction increased oxidative capacity, glucose transporter, and mitochondrial biogenesis. which are key determinants of the pleiotropic effects of exercise training.

Objective. The objective of the present study was to provide genomic and transcriptomic information that may improve clinical outcomes for locally advanced cervical cancer (LACC) patients by searching for therapeutic targets or potential biomarkers through the analysis of significantly altered signaling pathways in LACC. Methods. Microarray-based transcriptome profiling of 89 tumor samples from women with LACC was per formed. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, significantly over-expressed genes in LACC were identified; these genes were validated by quantitative reverse transcription-polymerase chain reaction in an independent cohort, and the protein expression data were obtained from the Human Protein Atlas. Results. A transcriptome analysis revealed 7530 significantly over-expressed genes in LACC samples. By KEGG analysis, we found 93 dysregulated signaling pathways, including the JAK-STAT, NOTCH and mTOR-autophagy pathways, which were significantly upregulated. We confirmed the overexpression of the relevant genes of each pathway, such as NOTCH1, JAK2, STAM1, SOS1, ADAM17, PSEN1, NCSTN, RPS6, STK11/LKB1 and MLTS8/GBL in LACC compared with normal cervical tissue epithelia. Conclusions. Through comprehensive genomic and transcriptomic analyses, this work provides information regarding signaling pathways with promising therapeutic targets, suggesting novel target therapies to be considered in future clinical trials for LACC patients. (C) 2016 The Authors. Published by Elsevier Inc.