ECCENTRIC EXERCISE POTENTLY ACTIVATES c-JUN NH2 TERMINAL KINASE(JNK) SIGNALING IN HUMAN SKELETAL MUSCLE

Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 ± 4.5 vs. 3.5 ± 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle.

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The heat shock protein response following eccentric exercise in human skeletal muscle is unaffected by local NSAID infusion

European Journal of Applied Physiology ◽

10.1007/s00421-013-2606-y ◽

2013 ◽

Vol 113 (7) ◽

pp. 1883-1893 ◽

Cited By ~ 12

Author(s):

U. R. Mikkelsen ◽

G. Paulsen ◽

P. Schjerling ◽

I. C. Helmark ◽

H. Langberg ◽

...

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Protein ◽

Eccentric Exercise ◽

Human Skeletal Muscle ◽

Protein Response

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399 ECCENTRIC EXERCISE DECREASES GLUT4 PROTEIN CONCENTRATION IN HUMAN SKELETAL MUSCLE

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-199405001-00400 ◽

1994 ◽

Vol 26 (Supplement) ◽

pp. S71

Author(s):

J. R. Daugaard ◽

S. Asp ◽

E. A. Richter

Keyword(s):

Skeletal Muscle ◽

Eccentric Exercise ◽

Protein Concentration ◽

Human Skeletal Muscle

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Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies

The Journal of Physiology ◽

10.1111/j.1469-7793.2000.00243.x ◽

2000 ◽

Vol 529 (1) ◽

pp. 243-262 ◽

Cited By ~ 212

Author(s):

Christer Malm ◽

Pernilla Nyberg ◽

Marianne Engström ◽

Bertil Sjödin ◽

Rodica Lenkei ◽

...

Keyword(s):

Skeletal Muscle ◽

Eccentric Exercise ◽

Human Skeletal Muscle ◽

Multiple Biopsies ◽

Immunological Changes

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Activation of NF-kB in Pericytes of Human Skeletal Muscle Following Eccentric Exercise-Induced Damage

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000389457.55524.d4 ◽

2010 ◽

Vol 42 ◽

pp. 96 ◽

Cited By ~ 1

Author(s):

Robert D. Hyldahl ◽

Ling Xin ◽

Monica J. Hubal ◽

Stephanie Moekel-Cole ◽

Stuart Chipkin ◽

...

Keyword(s):

Skeletal Muscle ◽

Eccentric Exercise ◽

Human Skeletal Muscle ◽

Exercise Induced

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Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol

Journal of Applied Physiology ◽

10.1152/japplphysiol.00441.2011 ◽

2011 ◽

Vol 111 (5) ◽

pp. 1448-1458 ◽

Cited By ~ 19

Author(s):

Robyn M. Murphy ◽

Kristian Vissing ◽

Heidy Latchman ◽

Cedric Lamboley ◽

Michael J. McKenna ◽

...

Keyword(s):

Skeletal Muscle ◽

Eccentric Exercise ◽

Repeated Measures ◽

Human Skeletal Muscle ◽

Exercise Intervention ◽

Calpain 3 ◽

Functional Consequences ◽

Exercise Induced ◽

Post Hoc ◽

Exercise In Humans

The skeletal muscle-specific calpain-3 protease is likely involved in muscle repair, although the mechanism is not known. Physiological activation of calpain-3 occurs 24 h following eccentric exercise in humans. Functional consequences of calpain-3 activation are not known; however, calpain-3 has been suggested to be involved in nuclear signaling via NF-κB. To test this and help identify how/where calpain-3 acts, we investigated whether calpain-3 autolysis (hence, activation) following eccentric exercise results in translocation from its normal myofibrillar location to the nucleus or the cytosol. In resting human skeletal muscle, the majority (87%) of calpain-3 was present in myofibrillar fractions, with only a small proportion (<10%) in an autolyzed state. Enriched nuclear fractions contained ∼8% of the total calpain-3, which was present in a predominantly (>80%) autolyzed state. Using freshly dissected human muscle fibers to identify freely diffusible proteins, we showed that only ∼5% of the total calpain-3 pool was cytosolic. At 3 and 24 h following eccentric step exercise, there was an ∼70% increase in autolysis in whole muscle samples ( n = 11, P < 0.05, by 1-way ANOVA with repeated measures and Newman-Keuls post hoc analysis). This exercise-induced autolysis was attributed to myofibrillar-bound calpain-3, since neither the amount of calpain-3 nor the proportion autolyzed was significantly changed in enriched nuclear or cytosolic fractions following the exercise intervention. We present a model for calpain-3 localization at rest and following activation in human skeletal muscle and suggest that the functional importance of calpain-3 remains predominantly tightly associated with its localization within the myofibrillar compartment.

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