Lethal Weight Loss: The Focus Shifts to Signal Transduction

Tracey, Kevin J.

doi:10.1126/stke.2002.130.pe21

Cited by 20 publications

(15 citation statements)

References 12 publications

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“…p38 MAPK is a stress-activated protein kinase that has been identified as a likely mediator of catabolic signaling in skeletal muscle (Tracey 2002). This is consistent with our results where increased phosphorylation of p38 MAPK was observed in the RP group compared with the control group.…”

Section: Discussionsupporting

confidence: 92%

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Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle

Engelbrecht

Smith

Neethling

et al. 2009

Stress

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Skeletal muscle protein loss, known as atrophy, occurs during inactivity, disease, and aging. Atrophy may be the result of increased catabolic factors, e.g. glucocorticoids, or reduced influence of anabolic factors, e.g. insulin. The purpose of this study was to investigate atrophy, signaling mechanisms, and apoptosis in a rat model of restraint stress in 40 adult male Wistar rats. Due to the anxiolytic effects of Sutherlandia frutescens, we also determined if any of the molecular events in gastrocnemius muscle would be affected by daily treatment with S. frutescens. Rats were randomly assigned to four experimental groups: control placebo (CP); control Sutherlandia (CS) treatment; Restraint Placebo (RP) and Restraint Sutherlandia (RS) treatment. Restraint resulted in a significant increase in myostatin which was significantly reduced with Sutherlandia treatment. In addition, MyoD expression was significantly attenuated in RP and this effect was also counteracted by Sutherlandia treatment. Restraint also resulted in a significant attenuation of the PI3-Kinase/Akt signaling pathway and increased apoptosis which was reversed with Sutherlandia treatment. This study demonstrates for the first time that psychological stress elevates markers of muscle atrophy and apoptosis, whilst a herbal remedy, Sutherlandia, inhibits apoptosis, and signaling pathways associated with muscle atrophy.

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Section: Discussionsupporting

confidence: 92%

“…Multiple processes related to atrophic events may contribute to the reduction of muscle fiber size and potential cellular role players include myostatin and p38 MAPK (Tracey 2002). Myostatin, a TGF-b family member, is involved in several forms of muscle wasting in adulthood (Durieux et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle

Engelbrecht

Smith

Neethling

et al. 2009

Stress

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show abstract

“…Mice producing antibodies to a novel antigen consume more oxygen than control animals [19]. Furthermore, many diseases, including cancer, diabetes mellitus, arthritis, AIDS and other infectious diseases, lead to significant energy deficits in humans, often resulting in cachexia [20]. Starvation and protein malnutrition compromises immune function [16].…”

mentioning

confidence: 99%

Seasonal immune function and sickness responses

Nelson

2004

Trends in Immunology

306

237

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“…These factors translocate to the nucleus, where they interact with specific DNA sequences to modulate the gene expression of c-fos or c-jun (28)(29)(30)(31)(32). Recently it has been shown that the increase of C/EBP-␤ leads to impaired organ function and protein synthesis, such as albumin (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…However, recently it was shown that the expression and synthesis of pro-and anti-inflammatory cytokines are controlled by several pro-and anti-inflammatory signal transcription factors. Signal transducer and activator of transcription (STAT-3 and -5) and CCCAT-enhancer binding protein-␤ (C/EBP-␤) belong to the proinflammatory signal transcription factors (10)(11)(12). Suppressors of cytokine signaling (SOCS-1, -2, -3) and regulated on activation, normally T cell-expressed and secreted (RANTES) belong to the group of signal transcription factors that exert anti-inflammatory effects by suppressing or attenuating proinflammatory cytokine expression, for example, suppressor of cylokine signaling (SOCS)-3 or regulating T-cell function, e.g., RANTES (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Differences in the Hepatic Signal Transcription Pathway and Cytokine Expression Between Thermal Injury and Sepsis

Klein

Einspanier²,

Bolder³

et al. 2003

Shock

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Inflammation and catabolism in response to trauma, surgery, critical illness or bacteria lead to a compromise of essential organs, which can lead to prolonged clinical stay and even death. Mediators responsible for catabolism were thought to be proinflammatory cytokines, but recently the focus has shifted to signal transduction. The purpose of the present study was to determine differences between two pathophysiologic states, sepsis and thermal injury, in signal transduction and cytokine expression and thus define the importance of the signal transcription pathway. Rats were randomly divided to either receive lipopolysaccharide (3 mg/kg body weight or a 30% total body surface area burn) or they received no treatment and served as controls. Animals were sacrificed 1, 2, 5, and 7 days postinsult and serum and liver harvested for analysis. A thermal injury appeared to have a slow release and expression of signal transcription factors and cytokines and a sepsis showed a rapid increase of mediators and also a fast decrease. The changes in cytokine profiles after burn, particularly interleukin-1beta and macrophage inhibitory factor, appear to be mediated by C/EBP-beta and STAT-3, whereas after the induction of a sepsis, tumor necrosis factor and interleukin-6 are mainly mediated by STAT-5. Based on our findings we suggest that the pathophysiologic state of a thermal injury is not comparable with sepsis in association with signal transcription factors and the differences in intracellular and extracellular signaling therefore opens new ideas for therapeutic options.

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Lethal Weight Loss: The Focus Shifts to Signal Transduction

Cited by 20 publications

References 12 publications

Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle

Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle

Seasonal immune function and sickness responses

Differences in the Hepatic Signal Transcription Pathway and Cytokine Expression Between Thermal Injury and Sepsis

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