Conditional independence mapping of DIGE data reveals PDIA3 protein species as key nodes associated with muscle aerobic capacity.
Bottom Line: Forty protein species were differentially (P<0.05, FDR<10%) expressed between HCR and LCR and conditional independence mapping found distinct networks within these data, which brought insight beyond that achieved by functional annotation.Instead we found that noncanonical STAT3 signalling may be associated with low exercise capacity and skeletal muscle insulin resistance.Moreover, we demonstrate that this novel approach can be applied to 2D gel analysis, which is unsurpassed in its ability to profile protein species but currently has few dedicated bioinformatic tools.
Affiliation: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK. Electronic address: email@example.com.Show MeSH
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Mentions: Two-way analysis of variance performed on the 696 gel spots matched in male and female soleus muscle of HCR and LCR rats detected 15 spots that were significantly (P < 0.05, FDR < 10%) different between males and females (Table 3) and 40 spots that were significantly (P < 0.05, FDR < 10%) different between HCR and LCR strains (Table 4). An image of the 2D reference gel annotated with the position of each of the statistically different protein spots is shown in Fig. 1. Overlap of spots that were different between HCR/LCR strain and those different between sexes was limited to 4 spots (#53 HSP7C, #139 SPA3K, #165 ODP2 and #379 ENOB) and just one spot (#379, β-enolase) exhibited a statistically significant interaction (more abundant in male LCR). β-Enolase is a highly abundant glycolytic enzyme and was resolved into 9 spots that had different pI but similar Mr. This spot pattern may reflect different states of modification. β-Enolase can undergo S, T and Y phosphorylation and K acetylation but proteome mining did not identify post-translational modifications specific to spot #379. Moreover, the 1.06-fold greater abundance of spot #379 specific to male LCR was somewhat overshadowed by the 2.57-fold greater abundance of β-enolase spot #410 that was observed in both male and female LCR (Table 4). Considering the wider effects on metabolic enzymes (Fig. 2), the greater abundance of β-enolase likely reflects a shift toward greater reliance on glycolytic metabolism in LCR muscle.
Affiliation: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK. Electronic address: firstname.lastname@example.org.