STAT3 signaling is activated in human skeletal muscle following acute resistance exercise

The transcription factor signal transducer and activator of transcription 3 (STAT3) has been identified as a mediator of cytokine signaling and implicated in hypertrophy; however, the importance of this pathway following resistance exercise in human skeletal muscle has not been investigated. In the present study, the phosphorylation and nuclear localization of STAT3, together with STAT3-regulated genes, were measured in the early recovery period following intense resistance exercise. Muscle biopsy samples from healthy subjects (7 males, 23.0 + 0.9 yr) were harvested before and again at 2, 4, and 24 h into recovery following a single bout of maximal leg extension exercise (3 sets, 12 repetitions). Rapid and transient activation of phosphorylated (tyrosine 705) STAT3 was observed at 2 h postexercise. STAT3 phosphorylation paralleled the transient localization of STAT3 to the nucleus, which also peaked at 2 h postexercise. Downstream transcriptional events regulated by STAT3 activation peaked at 2 h postexercise, including early responsive genes c-FOS (800-fold), JUNB (38-fold), and c-MYC (140-fold) at 2 h postexercise. A delayed peak in VEGF (4-fold) was measured 4 h postexercise. Finally, genes associated with modulating STAT3 signaling were also increased following exercise, including the negative regulator SOCS3 (60-fold). Thus, following a single bout of intense resistance exercise, a rapid phosphorylation and nuclear translocation of STAT3 are evident in human skeletal muscle. These data suggest that STAT3 signaling is an important common element and may contribute to the remodeling and adaptation of skeletal muscle following resistance exercise.

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Faculty Opinions recommendation of STAT3 signaling is activated in human skeletal muscle following acute resistance exercise.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1084942.537899 ◽

2007 ◽

Author(s):

Mark Hargreaves

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Human Skeletal Muscle ◽

Stat3 Signaling

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Resistance exercise increases NF-κB activity in human skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00336.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. R667-R673 ◽

Cited By ~ 56

Author(s):

Luke Vella ◽

Marissa K. Caldow ◽

Amy E. Larsen ◽

Daniella Tassoni ◽

Paul A. Della Gatta ◽

...

Keyword(s):

Skeletal Muscle ◽

Dna Binding ◽

Inflammatory Response ◽

Resistance Exercise ◽

Muscle Biopsy ◽

Human Skeletal Muscle ◽

Control Group ◽

Promoter Regions ◽

Protein Levels ◽

Single Bout

Intense resistance exercise causes a significant inflammatory response. NF-κB has been identified as a prospective key transcription factor mediating the postexercise inflammatory response. The purpose of this study was to determine whether a single bout of intense resistance exercise regulates NF-κB signaling in human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis of five recreationally active, but not strength-trained, males (21.9 ± 1.3 yr) prior to, and at 2 and 4 h following, a single bout of intense resistance exercise. A further five subjects (4 males, 1 female) (23 ± 0.89 yr) were recruited as a nonexercise control group to examine the effect of the muscle biopsy protocol on key markers of skeletal muscle inflammation. Protein levels of IκBα and phosphorylated NF-κB (p65), as well as the mRNA expression of inflammatory myokines monocyte chemoattractant protein 1 (MCP-1), IL-6, and IL-8 were measured. Additionally, NF-κB (p65) DNA binding to the promoter regions of MCP-1, IL-6, and IL-8 was investigated. IκBα protein levels decreased, while p-NF-κB (p65) protein levels increased 2 h postexercise and returned to near-baseline levels by 4-h postexercise. Immunohistochemical data verified these findings, illustrating an increase in p-NF-κB (p65) protein levels, and nuclear localization at 2 h postexercise. Furthermore, NF-κB DNA binding to MCP-1, IL-6, and IL-8 promoter regions increased significantly 2 h postexercise as did mRNA levels of these myokines. No significant change was observed in the nonexercise control group. These novel data provide evidence that intense resistance exercise transiently activates NF-κB signaling in human skeletal muscle during the first few hours postexercise. These findings implicate NF-κB in the transcriptional control of myokines known to be central to the postexercise inflammatory response.

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Faculty Opinions recommendation of Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1087589.540658 ◽

2007 ◽

Author(s):

Steve Rattigan

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Human Skeletal Muscle

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Faculty Opinions recommendation of Human skeletal muscle plasmalemma alters its structure to change its Ca(2+)-handling following heavy-load resistance exercise.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727304201.793528943 ◽

2017 ◽

Author(s):

Craig A Goodman

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Human Skeletal Muscle ◽

Load Resistance ◽

Heavy Load

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The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle

Experimental Gerontology ◽

10.1016/j.exger.2012.03.004 ◽

2012 ◽

Vol 47 (6) ◽

pp. 417-424 ◽

Cited By ~ 59

Author(s):

Zoltan Bori ◽

Zhongfu Zhao ◽

Erika Koltai ◽

Ioannis G. Fatouros ◽

Athanasios Z. Jamurtas ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Expression ◽

Physical Training ◽

Human Skeletal Muscle ◽

Mitochondrial Protein ◽

Single Bout ◽

Effects Of Aging

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Resistance Exercise Reverses Aging in Human Skeletal Muscle

PLoS ONE ◽

10.1371/journal.pone.0000465 ◽

2007 ◽

Vol 2 (5) ◽

pp. e465 ◽

Cited By ~ 191

Author(s):

Simon Melov ◽

Mark A. Tarnopolsky ◽

Kenneth Beckman ◽

Krysta Felkey ◽

Alan Hubbard

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Human Skeletal Muscle

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Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle

The Journal of Physiological Sciences ◽

10.1007/s12576-010-0130-y ◽

2011 ◽

Vol 61 (2) ◽

pp. 131-140 ◽

Cited By ~ 34

Author(s):

Ryo Kakigi ◽

Hisashi Naito ◽

Yuji Ogura ◽

Hiroyuki Kobayashi ◽

Norio Saga ◽

...

Keyword(s):

Skeletal Muscle ◽

Heat Stress ◽

Resistance Exercise ◽

Human Skeletal Muscle ◽

Mtor Signaling

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Abstract 3474: Cardiac -Specific SOCS3 Dificient Mice Shows Resistance to Lipopolysaccharide-Induced Cardiac Dysfunction

Circulation ◽

10.1161/circ.118.suppl_18.s_432-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Futamata Nobuyoshi ◽

Hldeo Yasukawa ◽

Toyoharu Ohba ◽

Kazutoshi Mawatari ◽

Daisuke Fukui ◽

...

Keyword(s):

Western Blot ◽

Left Ventricular ◽

Negative Regulator ◽

Left Ventricular Ejection ◽

Cytokine Signaling ◽

Rt Pcr ◽

Lv Dysfunction ◽

Stat3 Signaling ◽

Cardiomyocyte Survival

Background : Lypopolysaccharide (LPS)-induced left ventricular (LV) dysfunction is a well-established model for sepsis-induced acute heart failure. STAT3 signaling in the heart has been shown to promote cardiomyocyte survival during LPS-induced LV dysfunction. Little is known, however, about the role of negative regulation of STAT3 signaling during LPS-induced LV dysfunction. Suppressor of cytokine signaling 3 (SOCS3) is an intrinsic negative regulator of gp130 cytokine-induced STAT3 signaling that plays an important role in cardiomyocyte survival. In this study, we determined whether STAT3 signaling and its negative regulator SOCS3 would play a role in LPS-induced LV dysfunction. Methods and Results : We examined the activation of STAT3 and inductions of gp130 cytokines and SOCS3 in the wild-type (WT) mice hearts after LPS injection by western blot and real-time PCR (RT-PCR). RT-PCR revealed that gp130 cytokines were markedly increased after AMI. Western blot revealed that STAT3 was markedly phosphorylated and SOCS3 was induced in WT mice hearts after LPS injection. To investigate the role of STAT3 signaling and SOCS3 in LPS-induced LV dysfunction, we generated cardiac-specific SOCS3 knockout mice (SOCS3-CKO). Left ventricular ejection fraction (LVEF) of SOCS3-CKO mice was similar to that of WT mice at baseline (64.2 ± 6.1 vs. 62.4 ± 4.4%). LPS (30mg/kg) elicited a significant and robust reduction of LVEF in both SOCS3-CKO mice and WT mice 3 hr after LPS injection (18 ± 4.5 vs. 16 ± 5.2%, p <0.01). LVEF in WT mice was further reduced 6 hr after LPS injection. On the other hand, interestingly, LVEF was restored to the baseline in SOCS3-CKO mice 6 hr after LPS injection (10.4 ± 3.9 vs. 62.2 ± 8.1%, p <0.01). Also the duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Furthermore, SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection ( p <0.01). Conclusion : Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice, possibly by augmenting the STAT3-mediated gp130 cytokine signaling.

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