Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Kukreti, Himani; Kottaiswamy, Amuthavalli; Harikumar, Arigela; Sathiyamoorthy, Sushmitha; Feng, Peng Zhao; Anantharaj, Rengaraj; Tan, Suan Liang Kelvin; Lokireddy, Sudarsanareddy; Bonala, Sabeera; Sriram, Sandhya; McFarlane, Craig; Kambadur, Ravi; Sharma, Mridula

doi:10.1074/jbc.m112.390369

Cited by 108 publications

(96 citation statements)

References 46 publications

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“…Furthermore, upregulations of miR-1 in dexamethasone-mediated muscle atrophy in mice and atrophic signals, which are integrated by miR-1, have been reported (19). In addition, it has been reported that miR-1 targets HSP72 during dexamethasone-mediated myotube atrophy (21). In the present study, it is shown that AICAR-induced AMPK activation upregulated miR-1, and this alteration was not seen in the AMPK␣ knockdown condition (Fig.…”

Section: Discussionsupporting

confidence: 57%

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells

Egawa

Ohno

Goto

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells. Am J Physiol Endocrinol Metab 306: E344 -E354, 2014. First published December 17, 2013; doi:10.1152/ajpendo.00495.2013.-5=-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock transcription factor 1 in myotubes. Protein content and diameter were less in the AICARtreated myotubes in those without treatment. AICAR-induced suppression of myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated AMPK␣ knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of HSP72, and the increase of miR-1 was not induced in AMPK␣ knockdown condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICARinduced inhibition of myotube hypertrophy. AICAR upregulated the gene expression of muscle Ring-finger 1, and this alteration was suppressed in either AMPK␣ or HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr 389 was downregulated by AICAR, whereas this was attenuated in AMPK␣, but not in HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy through, in part, an HSP72-associated mechanism via miR-1 and protein degradation pathways in skeletal muscle cells. microRNA; heat shock transcription factor 1; muscle rRing-finger 1; atrogin-1; acetyl-CoA carboxylase SKELETAL MUSCLE HAS A GREATER CAPACITY to adapt to various stimuli. Increased loading, such as resistance training and mechanical stretching, stimulates protein synthesis and reduces protein degradation, thereby inducing muscle hypertrophy (10). On the other hand, decrease of use, such as immobilization, denervation, aging, and/or various pathological conditions, attenuates protein synthesis and increases protein degradation, resulting in atrophy (12,32). Although the process of skeletal muscle adaptation to hypertrophic and atrophic stimuli has been studied, the molecular mechanism involved in this process is not fully understood yet.5=-AMP-activated protein kinase (AMPK) is well known as a sensor for cellular energy status and metabolic stress, such as muscle contraction, fasting, hypoxia, ischemia, and/or oxidative and osmotic stresses and as a signaling intermediary that controls the use of glucose and fatty acids in skeletal muscle (8,14,15). In addition, several studies in the past decade have suggested that AMPK plays an important rol...

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Section: Discussionsupporting

confidence: 57%

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells

Egawa

Ohno

Goto

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…The same anti‐ pF oxO3 antibody was used in previous publications (Kukreti et al. 2013; Tarrado‐Castellarnau et al. 2015).…”

Section: Resultsmentioning

confidence: 99%

Paradoxical effect of IKKβ inhibition on the expression of E3 ubiquitin ligases and unloading-induced skeletal muscle atrophy

et al. 2017

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We tested whether NF‐κB pathway is indispensable for the increase in expression of E3‐ligases and unloading‐induced muscle atrophy using IKKβ inhibitor IMD‐0354. Three groups of rats were used: nontreated control (C), 3 days of unloading/hindlimb suspension with (HS+IMD) or without (HS) IMD‐0354. Levels of IκBα were higher in HS+IMD (1.16‐fold) and lower in HS (0.82‐fold) when compared with C group. IMD‐0354 treatment during unloading: had no effect on loss of muscle mass; increased mRNA levels of MuRF1 and MAFbx; increased level of pFoxO3; and had no effect on levels of Bcl‐3, p105, and p50 proteins. Our study for the first time showed that inhibiting IKK β in vivo during 3‐day unloading failed to diminish expression of ubiquitin ligases and prevent muscle atrophy.

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“…However, no studies have investigated whether miRNA expression is altered following concurrent compared with single-mode RE. The myomiRs miR-1 and miR-133a can target members of the IGF-1/Akt pathway in vitro, including IGF-1 (35), the IGF-1 receptor (35), as well as HSP70 (54). This suggests they may play a role in regulating muscle hypertrophy, although this requires experimental validation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle

Fyfe

Bishop

Zacharewicz

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Fyfe JJ, Bishop DJ, Zacharewicz E, Russell AP, Stepto NK. Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 310: R1297-R1311, 2016. First published April 13, 2016 doi:10.1152/ajpregu.00479.2015.-We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean Ϯ SD: age, 27 Ϯ 4 yr; V O2 peak, 45.7 Ϯ 9 ml·kg Ϫ1 ·min Ϫ1 ) performed three experimental trials in a randomized order: 1) RE (8 ϫ 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 ϫ 2 min at 120% lactate threshold (LT); HIT ϩ RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT ϩ RE). Vastus lateralis muscle biopsies were obtained immediately before RE, either without (REST) or with (POST) preceding endurance exercise and ϩ1 h (RE ϩ 1 h) and ϩ3 h (RE ϩ 3 h) after RE. Prior HIT and MICT similarly reduced muscle glycogen content and increased ACC Ser79 and p70S6K Thr389 phosphorylation before subsequent RE (i.e., at POST). Compared with MICT, HIT induced greater mTOR Ser2448 and rps6 Ser235/236 phosphorylation at POST. REinduced increases in p70S6K and rps6 phosphorylation were not influenced by prior HIT or MICT; however, mTOR phosphorylation was reduced at RE ϩ 1 h for MICT ϩ RE vs. both HIT ϩ RE and RE. Expression of miR-133a, miR-378, and miR-486 was reduced at RE ϩ 1 h for HIT ϩ RE vs. both MICT ϩ RE and RE. Postexercise mTORC1 signaling following RE is therefore not compromised by prior HIT or MICT, and concurrent exercise incorporating HIT, but not MICT, reduces postexercise expression of miRNAs implicated in skeletal muscle adaptation to RE. concurrent training; interference; exercise intensity; high-intensity interval training; continuous training INCORPORATING BOTH RESISTANCE (RE) and endurance exercise into a periodized training program is termed concurrent training (56). Compared with undertaking RE alone, concurrent training attenuates skeletal muscle hypertrophy and maximal strength development in some (10,19,33,48,53), but not all (5,58,63,75,76), studies. Given that skeletal muscle mass plays an important role in overall metabolic health (87), and many athletes require elements of strength and muscle hypertrophy, concomitantly with a high aerobic capacity (47), minimizing interference during concurrent training has implications for optimizing both health and performance outcomes.

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Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Cited by 108 publications

References 46 publications

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells

Paradoxical effect of IKKβ inhibition on the expression of E3 ubiquitin ligases and unloading-induced skeletal muscle atrophy

Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle

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Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Cited by 108 publications

References 46 publications

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12skeletal muscle cells

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12skeletal muscle cells

Paradoxical effect of IKKβ inhibition on the expression of E3 ubiquitin ligases and unloading-induced skeletal muscle atrophy

Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle

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AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C₂C₁₂skeletal muscle cells