(625.1) Phosphoproteomic profiling of skeletal muscle twitch torque potentiation in ovarian hormone deficient female mice

Poster Board Number: E665

Mina Peyton (University of Minnesota), Tzu Yi Yang (Harvard Medical School), LeeAnn Higgins (University of Minnesota), Laurie Parker (University of Minnesota), Dawn Lowe (University of Minnesota)

Skeletal muscle makes up ~40% of total body mass in a healthy adult. Muscle strength begins to decline with age. In females, preclinical and clinical studies have shown that reduction in estrogen reduces muscle force (i.e., strength). Previously, we showed the skeletal muscle phosphoproteome in a basal, non-contracting state was remodeled in estrogen-deficient females. Therefore, we questioned how estrogen deficiency would impact the skeletal muscle phosphoproteome after force generation. We performed two label-free quantification phosphoproteomic analyses of the tibialis anterior muscle in ovariectomized (Ovx/Sham) and ovarian senescent (Old/Young) female mice after in vivo post-tetanic potentiation protocol. We identified 25 and 60 differentially regulated phosphoproteins (p-valuelt;0.05 and ≥1.4-fold change) in Ovx/Sham and Old/Young mice, respectively. Comparative analysis using Ingenuity Pathway Analysis’s activation Z-score found similar patterns of predicted inhibition and activation of canonical pathways, such as inhibition of calcium signaling and activation of 14-3-3-mediated signaling in both datasets. Likewise, parallel patterns in functional analysis were found relating to muscle contraction, fibrogenesis, etc. Overall, our findings suggest that the similarities identified in both datasets could elucidate the molecular characteristics of muscle proteins that might contribute to decrements in muscle function observed in Ovx and Old females due to the loss of estrogen.

This work was supported by the National Institutes of Health R01 AG031743-13 and Training Program in Muscle Research T32 AR007612 grants.