Sepsis stimulates release of myofilaments in skeletal muscle by a calcium‐dependent mechanism

Williams, Amanda D.; Decourten-Myers, Gabrielle; Fischer, Josef E.; Luo, Guangju; Sun, Xiaoyan; Hasselgren, Per-Olof

doi:10.1096/fasebj.13.11.1435

Cited by 172 publications

(148 citation statements)

References 51 publications

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“…In this regard, we cannot exclude that activation of Ca 2+ -dependent proteolysis might even precede bulk protein hypercatabolism and play a causative role in establishing this metabolic response. Although quite speculative so far, the latter hypothesis may be consistent with the report that the release of myofilament proteins from the skeletal muscle in sepsis is likely associated with activation of Ca 2+ -dependent proteolysis (Williams et al, 1999b), while activation of the ATP-ubiquitindependent proteolytic system would be the consequence of an increased availability of substrates rather than the primary cause of muscle protein breakdown (Williams et al, 1999b). Finally, the recent report (Busquets et al, 2000) that the expression of the muscle-specific calpain p94 is significantly reduced may also be relevant to the present findings.…”

Section: Discussionsupporting

confidence: 84%

Activation of Ca2+-dependent proteolysis in skeletal muscle and heart in cancer cachexia

et al. 2001

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Cachexia is a syndrome characterized by profound tissue wasting that frequently complicates malignancies. In a cancer cachexia model we have shown that protein depletion in the skeletal muscle, which is a prominent feature of the syndrome, is mostly due to enhanced proteolysis. There is consensus on the views that the ubiquitin/proteasome pathway plays an important role in such metabolic response and that cytotoxic cytokines such as TNFα are involved in its triggering (Costelli and Baccino, 2000), yet the mechanisms by which the relevant extracellular signals are transduced into protein hypercatabolism are largely unknown. Moreover, little information is presently available as to the possible involvement in muscle protein waste of the Ca 2+ -dependent proteolysis, which may provide a rapidly activated system in response to the extracellular signals. In the present work we have evaluated the status of the Ca 2+ -dependent proteolytic system in the gastrocnemius muscle of AH-130 tumour-bearing rats by assaying the activity of calpain as well as the levels of calpastatin, the natural calpain inhibitor, and of the 130 kDa Ca 2+ -ATPase, both of which are known calpain substrates. After tumour transplantation, total calpastatin activity progressively declined, while total calpain activity remained unchanged, resulting in a progressively increasing unbalance in the calpain/calpastatin ratio. A decrease was also observed for the 130 kDa plasma membrane form of Ca 2+ -ATPase, while there was no change in the level of the 90 kDa sarcoplasmic Ca 2+ -ATPase, which is resistant to the action of calpain. Decreased levels of both calpastatin and 130 kDa Ca 2+ -ATPase have been also detected in the heart of the tumour-bearers. These observations strongly suggest that Ca 2+ -dependent proteolysis was activated in the skeletal muscle and heart of tumour-bearing animals and raise the possibility that such activation may play a role in sparking off the muscle protein hypercatabolic response that characterizes cancer cachexia. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionsupporting

confidence: 84%

Activation of Ca2+-dependent proteolysis in skeletal muscle and heart in cancer cachexia

et al. 2001

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“…4c-e), in agreement with the previously reported Ca 2? -dependent expression and function of this protease in skeletal muscle [42]. Notably, the up-regulation of Cx43 induced by S1P also required m-calpain activation.…”

Section: Trpc1/ca 2? Channels Are Involved In Cx43 Expression/ Functimentioning

confidence: 94%

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Meacci

Bini

Sassoli

et al. 2010

Cell. Mol. Life Sci.

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We recently demonstrated that skeletal muscle differentiation induced by sphingosine 1-phosphate (S1P) requires gap junctions and transient receptor potential canonical 1 (TRPC1) channels. Here, we searched for the signaling pathway linking the channel activity with Cx43 expression/function, investigating the involvement of the Ca 2? -sensitive protease, m-calpain, and its targets in S1P-induced C2C12 myoblast differentiation. Gene silencing and pharmacological inhibition of TRPC1 significantly reduced Cx43 up-regulation and Cx43/cytoskeletal interaction elicited by S1P. TRPC1-dependent functions were also required for the transient increase of m-calpain activity/expression and the subsequent decrease of PKCa levels. Remarkably, Cx43 expression in S1P-treated myoblasts was reduced by m-calpain-siRNA and enhanced by pharmacological inhibition of classical PKCs, stressing the relevance for calpain/PKCa axis in Cx43 protein remodeling. The contribution of this pathway in myogenesis was also investigated. In conclusion, these findings provide novel mechanisms by which S1P regulates myoblast differentiation and offer interesting therapeutic options to improve skeletal muscle regeneration.

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“…Calpains are activated during sepsis-induced muscle injury [26] and resistive loadinginduced diaphragm damage [6,16]. In contrast to the other factors, p94 mRNA did not decrease, but peaked transiently and immediately after injury, simultaneously with maximum sarcolemmal injury and loss of force [2].…”

Section: Pattern Of Gene Activationmentioning

confidence: 96%

Time-based gene expression programme following diaphragm injury in a rat model

Mehiri

Barreiro²,

Hayot³

et al. 2005

European Respiratory Journal

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It was hypothesised that diaphragm injury activates a time-based programme of gene expression in muscle repair.Gene expression of different substances, such as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos), growth factors (both basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced injury. Injured and noninjured (control) rat hemidiaphragms were excised at different time points (1-240 h).In injured hemidiaphragms, in comparison with control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were significantly elevated at 72 h PI.Caffeine-induced diaphragm injury is followed by a time-based expression programme of different genes tailored to meet muscle repair needs.

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Sepsis stimulates release of myofilaments in skeletal muscle by a calcium‐dependent mechanism

Cited by 172 publications

References 51 publications

Activation of Ca2+-dependent proteolysis in skeletal muscle and heart in cancer cachexia

Activation of Ca2+-dependent proteolysis in skeletal muscle and heart in cancer cachexia

Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Time-based gene expression programme following diaphragm injury in a rat model

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