scholarly journals Global phosphoproteomic profiling of skeletal muscle in ovarian hormone-deficient female mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 675-676
Author(s):  
Mina Peyton ◽  
Tzu-Yi Yang ◽  
LeeAnn Higgins ◽  
Todd Markowski ◽  
Laurie Parker ◽  
...  

Abstract Dynapenia, the age-related loss of skeletal muscle strength without the loss of muscle mass, significantly impacts the activities and quality of life of the aging population. Studies have shown that dynapenia occurs earlier in females than males in both human and rodent studies. Moreover, in females, estrogen deficiency has been shown to contribute to the loss of skeletal muscle strength as well as blunted recovery of strength after injury. The maintenance of skeletal muscle contractile function is vital to the overall health of women, especially as women live 1/3 of their life in an estrogen deficient state. Reversible protein phosphorylation is an indispensable post-translational modification, playing a key role in signal transduction pathways. Phosphorylation of skeletal muscle proteins have been shown to regulate sarcomeric function, excitation-contraction coupling, energy metabolism, and fiber-type composition. To define the physiological changes in the skeletal muscle phosphoproteome associated with estrogen deficiency, we used an ovariectomy model coupled with mass spectrometry. We identified, in total, 5,424 unique phosphorylation sites and 1,177 phosphoproteins in the tibialis anterior muscle. Ingenuity Pathway Analysis show decreased phosphorylation of contractile proteins and significant predicted inhibition of the upstream kinase, CDK6 (z-score -2.0) in ovariectomized compared to control muscles. Our results suggest that estrogen deficiency remodels the skeletal muscle phosphoproteome which may alter phosphorylation signaling that might contribute to the loss of strength in females.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249472
Author(s):  
Pangdra Vang ◽  
Cory W. Baumann ◽  
Rebecca Barok ◽  
Alexie A. Larson ◽  
Brendan J. Dougherty ◽  
...  

Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury.


2000 ◽  
Vol 88 (4) ◽  
pp. 1321-1326 ◽  
Author(s):  
Walter R. Frontera ◽  
Virginia A. Hughes ◽  
Roger A. Fielding ◽  
Maria A. Fiatarone ◽  
William J. Evans ◽  
...  

The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985–86 (T1) and nine (initial mean age 65.4 ± 4.2 yr) were reevaluated in 1997–98 (T2). Isokinetic muscle strength of the knee and elbow extensors and flexors showed losses ( P < 0.05) ranging from 20 to 30% at slow and fast angular velocities. Computerized tomography ( n = 7) showed reductions ( P < 0.05) in the cross-sectional area (CSA) of the thigh (12.5%), all thigh muscles (14.7%), quadriceps femoris muscle (16.1%), and flexor muscles (14.9%). Analysis of covariance showed that strength at T1 and changes in CSA were independent predictors of strength at T2. Muscle biopsies taken from vastus lateralis muscles ( n = 6) showed a reduction in percentage of type I fibers (T1 = 60% vs. T2 = 42%) with no change in mean area in either fiber type. The capillary-to-fiber ratio was significantly lower at T2 (1.39 vs. 1.08; P = 0.043). Our observations suggest that a quantitative loss in muscle CSA is a major contributor to the decrease in muscle strength seen with advancing age and, together with muscle strength at T1, accounts for 90% of the variability in strength at T2.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.


2016 ◽  
Vol 17 (3) ◽  
pp. 497-510 ◽  
Author(s):  
Michael McLeod ◽  
Leigh Breen ◽  
D. Lee Hamilton ◽  
Andrew Philp

2011 ◽  
Vol 31 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Jonathan Singer ◽  
Edward H. Yelin ◽  
Patricia P. Katz ◽  
Gabriela Sanchez ◽  
Carlos Iribarren ◽  
...  

2017 ◽  
Vol 15 (6) ◽  
pp. 434-439 ◽  
Author(s):  
Gao-feng Zhu ◽  
Zhi-fang Shen ◽  
Qing-he Shen ◽  
Yue-qin Jin ◽  
Zhi-yong Lou

2007 ◽  
Vol 117 (1) ◽  
pp. 277-277
Author(s):  
Foteini Mourkioti ◽  
Paschalis Kratsios ◽  
Tom Luedde ◽  
Yao-Hua Song ◽  
Patrick Delafontaine ◽  
...  

2009 ◽  
Vol 107 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Lori S. Kang ◽  
SeJeong Kim ◽  
James M. Dominguez ◽  
Amy L. Sindler ◽  
Gregory M. Dick ◽  
...  

Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent evidence indicates that both large-conductance Ca2+-activated (BKCa) and voltage-dependent (KV) K+ channels mediate negative feedback control of the myogenic response. Thus we tested the hypothesis that aging increases the contributions of KV and BKCa channels to myogenic regulation of vascular tone. Because myogenic responsiveness differs between oxidative and glycolytic muscles, we predicted that KV and BKCa channel contributions to myogenic responsiveness vary with fiber type. Myogenic responses of first-order arterioles from the gastrocnemius and soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors of KV and BKCa, respectively. 4-Aminopyridine enhanced myogenic tone with aging and normalized age-related differences in both muscle types. By contrast, iberiotoxin eliminated age-related differences in soleus arterioles and had no effect in gastrocnemius vessels. KV1.5 is an integral component of KV channels in vascular smooth muscle; therefore, we determined the relative protein expression of KV1.5, as well as BKCa, in soleus and gastrocnemius arterioles. Immunoblot analysis revealed no differences in KV1.5 protein with aging or between variant fiber types, whereas BKCa protein levels declined with age in arterioles from both muscle groups. Collectively, these results suggest that the contribution of BKCa to myogenic regulation of vascular tone changes with age in soleus muscle arterioles, whereas increased KV channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.


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