bims-prodis 2018-09-23 papers

Issue of 2018–09–23
two papers selected by
Nancy Gough, Bioserendipity

Free Radic Biol Med. 2018 Sep 13. pii: S0891-5849(18)31592-2. [Epub ahead of print]

Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle.

James N Cobley, Giorgos K Sakellariou, Holger Husi, Brian McDonagh.

Increased oxidative damage and disrupted redox signalling are consistently associated with age-related loss of skeletal muscle mass and function. Redox signalling can directly regulate biogenesis and degradation pathways and indirectly via activation of key transcription factors. Contracting skeletal muscle fibres endogenously generate free radicals (e.g. superoxide) and non-radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling can promote beneficial adaptive responses that are disrupted by age-related redox changes. Identifying and quantifying the redox signalling pathways responsible for successful adaptation to exercise makes skeletal muscle an attractive physiological model for redox proteomic approaches. Site specific identification of the redox modification and quantification of site occupancy in the context of protein abundance remains a crucial concept for redox proteomics approaches. Notwithstanding, the technical limitations associated with skeletal muscle for proteomic analysis, we discuss current approaches for the identification and quantification of transient and stable redox modifications that have been employed to date in ageing research. We also discuss recent developments in proteomic approaches in skeletal muscle and potential implications and opportunities for investigating disrupted redox signalling in skeletal muscle ageing.

Keywords: Ageing; Exercise; ROS; Redox Proteomics; Skeletal muscle

DOI: https://doi.org/10.1016/j.freeradbiomed.2018.09.012

Clin Sci (Lond). 2018 Sep 28. 132(18): 2029-2044

Proteomic analysis of exosomes reveals an association between cell invasiveness and exosomal bioactivity on endothelial and mesenchymal cell migration in vitro.

Shayna Sharma, Mona Alharbi, Miharu Kobayashi, Andrew Lai, Dominic Guanzon, Felipe Zuñiga, Valeska Ormazabal, Carlos Palma, Katherin Scholz-Romero, Gregory E Rice, John D Hooper, Carlos Salomon.

Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In the present study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and buoyant density centrifugation and characterised using nanoparticle tracking analysis (NTA), Western blot, and EM. Exosome secretion was positively correlated with invasiveness of releasing cells. Proteomic analyses identified common and unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology analyses revealing that these exosomes are involved in the regulation of cell migration. Since the tumour microenvironment contains multiple cell types, including MSCs and ECs, we examined the effect of these exosomes on MSC and EC migration. Exosomes promoted MSC and EC migration in a time- and concentration-dependent manner. The effect of exosomes isolated from SKOV-3 on cell migration was significantly higher compared with exosomes from OVCAR-3. Thus, we suggest that exosomes from ovarian cancer cells contain a specific set of proteins that are representative of its cell of origin and the invasive capacity.

Keywords: Exosomes; Ovarian cancer; tumour microenvironment

DOI: https://doi.org/10.1042/CS20180425