Regulation of p70S6k, GSK-3β, and calcineurin in rat striated muscle during aging

Kinnard, Randy S.; Mylabathula, Deepak B.; Uddemarri, S.; Rice, Kevin M.; Wright, Gary L.; Blough, Eric R.

doi:10.1007/s10522-005-7953-6

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…Parkington et al (2004) reported stability of total p70S6K with age in rat PL and tibialis anterior (TA) and increased phosphorylation of p70S6K T389 in TA only. In contrast, Kinnard et al (2005) reported decreased p70S6K and increased p70S6K T389 with age in the rat EDL and soleus. We previously noted decline in total p70S6K and p70S6K 421/424 but no change in p70S6K T389 in the rat biceps brachii with age and stability of all in the rat SG (Rahnert et al, 2011) suggesting difference in p70S6K signaling with age in rat versus macaque tongue muscle.…”

Section: 4 Discussionmentioning

confidence: 72%

Absence of morphological and molecular correlates of sarcopenia in the macaque tongue muscle styloglossus

Sokoloff

Douglas

Rahnert

et al. 2016

Experimental Gerontology

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Introduction Equivocal decline of tongue muscle performance with age is compatible with resistance of the tongue to sarcopenia, the loss of muscle volume and function that typically occurs with aging. To test this possibility we characterized anatomical and molecular indices of sarcopenia in the macaque tongue muscle styloglossus (SG). Methods We quantified myosin heavy chain (MHC), muscle fiber MHC phenotype and size and total and phosphorylated growth- and atrophy-related proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblot and immunohistochemistry (IHC) in the SG in twenty-four macaque monkeys (Macaca rhesus, age range 9 months to 31 years) categorized into Young (<8 years of age), Middle-aged (15–21 years of age) and Old (> 22 years of age) groups. Results In Young, Middle and Old age groups, by SDS-PAGE MHCI comprised ~1/3 and MHCII ~2/3 of total MHC. MHCI relative frequency was lower and MHCII higher in Middle versus Young (p=0.0099) and Middle versus Old (p=0.052). Relative frequencies of MHC fiber phenotype were not different by age but were different by phenotype (rates 233, 641 and 111 per 1000 fibers for MHCI, MHCII and MHCI-II respectively, P = 0.03). Few or no fibers were positive for developmental MHC. Mean cross-sectional area (CSA) was not different among the three age groups for MHCII and MHCI-II; however MHCI fibers tended to be larger in Middle versus Old and Young (mean = 2257 um2, 1917 um2 (p=0.05) and 1704 um2 (p=0.06), respectively). For each age group, mean CSA increased across MHC phenotype (lowest mean CSA for MHCI and highest mean CSA for MHCII). Spearman analysis demonstrated age-related increases in total p70 ribosomal protein S6 kinase (P70), phosphorylated P70421/424, phosphorylated P38 mitogen-activated protein kinase and muscle atrophy F-Box, a trend to age-related decrease in total extracellular signal-regulated kinase (ERK), and no age-related change in total protein kinase B (Akt/PKB), phosphorylated Akt, phosphorylated ERK, phosphorylated c-Jun N-terminal kinase (JNK46) and phosphorylated P70389. Conclusion Common anatomical and molecular indices of sarcopenia are absent in our sample of macaque SG. Relative frequencies of MHCII protein and phenotype are preserved with age. Although MAFbx expression increases with age, this is not associated with fiber atrophy, perhaps reflecting compensatory growth signaling by p70. The resistant nature of the styloglossus muscle to sarcopenia may be related to routine activation of tongue muscles in respiration and swallowing and the preservation of hypoglossal motoneuron number with age.

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Section: 4 Discussionmentioning

confidence: 72%

Absence of morphological and molecular correlates of sarcopenia in the macaque tongue muscle styloglossus

Sokoloff

Douglas

Rahnert

et al. 2016

Experimental Gerontology

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“…Furthermore, GSK-3β activity has been shown to increase in aging and correlate to sarcopenia (Kinnard et al, 2005). Therefore, GSK-3β was measured by Western blot as an indicator of altering catabolic signaling potential during myogenic recovery after disuse.…”

Section: Resultsmentioning

confidence: 99%

Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats

Alway

Bennett

Wilson

et al. 2014

Experimental Gerontology

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Aging exacerbates muscle loss and slows the recovery of muscle mass and function after disuse. In this study we investigated the potential that epigallocatechin gallate (EGCg), an abundant catechin in green tea, would reduce signaling for apoptosis and promote skeletal muscle recovery in the fast plantaris muscle and the slow soleus muscle after hindlimb unloading (HLS) in senescent animals. Fischer 344 × Brown Norway inbred rats (age 34 mo.) received either EGCg (50 mg/kg body weight), or water daily by gavage. One group of animals received HLS for 14 days and a second group of rats received 14 days of HLS, then the HLS was removed and they recovered from this forced disuse for 2 weeks. Animals that received EGCg over the HLS followed by 14 days of recovery, had a 14% greater plantaris muscle weight (p <0.05) as compared to the animals treated with the vehicle over this same period. Plantaris fiber area was greater after recovery in EGCg (2715.2 ± 113.8 μm2) vs. vehicle treated animals (1953.0 ± 41.9 μm2). In addition, activation of myogenic progenitor cells was improved with EGCg over vehicle treatment (7.5% vs. 6.2%) in the recovery animals. Compared to vehicle treatment, the apoptotic index was lower (0.24% vs. 0.52%), and the abundance of pro-apoptotic proteins Bax (−22%), and FADD (−77%) were lower in EGCg treated plantaris muscles after recovery. While EGCg did not prevent unloading-induced atrophy, it improved muscle recovery after the atrophic stimulus in fast plantaris muscles. However, this effect was muscle specific because EGCg had no major impact in reversing HLS-induced atrophy in the slow soleus muscle of old rats.

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“…Studies in skeletal muscles have linked GSK-3b to muscle-wasting conditions. GSK-3b activity has been shown to increase in aged (Kinnard et al, 2005) and burn-injured skeletal muscles (Fang et al, 2007). Inhibition of GSK-3b is required for IGF-1-induced myogenic differentiation (Vyas et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Suppression of GSK-3β activation by M-cadherin protects myoblasts against mitochondria-associated apoptosis during myogenic differentiation

Wang

Hao

2011

Journal of Cell Science

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Apoptosis occurs concurrently with differentiation of muscle progenitor cells (MPCs) before they fuse to form myotubes. Dysregulated apoptosis in MPCs contributes to the low regeneration capability in aged muscle and decreases the survival rate of donor cells in stem cell-based therapies for muscular dystrophies. This study investigated the role of the M-cadherin/PI3K/Akt/GSK-3β signaling pathway in regulating apoptosis during differentiation of MPCs. Disruption of M-cadherin-dependent cell-cell adhesion by M-cadherin RNA interference in confluent C2C12 myoblasts sensitized the cells to mitochondria-associated intrinsic apoptosis induced by cell confluence or serum starvation. Further investigation of this pathway revealed that M-cadherin-mediated signaling suppressed GSK-3β activation by enhancing the PI3K/AKT-dependent inhibitory phosphorylation of Ser9 in GSK-3β. Overexpression of wild-type GSK-3β in confluent C2C12 myoblasts exacerbated the apoptosis, whereas chemical inhibition of GSK-3β using TDZD-8, or forced expression of constitutively active Akt (myrAkt), or a kinase-deficient GSK-3β mutant [GSK-3β(K85R)], attenuated apoptosis and rescued the impaired myogenic differentiation that is caused by M-cadherin RNA interference. These data suggest that M-cadherin-mediated signaling prevents acceleration of mitochondria-associated intrinsic apoptosis in MPCs by suppressing GSK-3β activation during myogenic differentiation.

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Regulation of p70S6k, GSK-3β, and calcineurin in rat striated muscle during aging

Cited by 16 publications

References 33 publications

Absence of morphological and molecular correlates of sarcopenia in the macaque tongue muscle styloglossus

Absence of morphological and molecular correlates of sarcopenia in the macaque tongue muscle styloglossus

Epigallocatechin-3-gallate improves plantaris muscle recovery after disuse in aged rats

Suppression of GSK-3β activation by M-cadherin protects myoblasts against mitochondria-associated apoptosis during myogenic differentiation

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