Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?

Orzechowski, Arkadiusz; Grizard, Jean; Jank, Michał; Gajkowska, B; Lokociejewska, M.; Zaron-Teperek, Magda; Godlewski, M

doi:10.1051/rnd:2002018

Cited by 28 publications

(24 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At short times of exposure, H 2 O 2 , triggers the activation of a defense response, whereas at long treatment times, the programmed cell death finally starts, and it is at this time that testosterone carries out its protective action against apoptosis. H 2 O 2 has been shown to act as a signaling molecule involved in many cellular functions such as apoptosis (Singh & Singh 2008, Vasconsuelo et al 2008, differentiation (Steinbeck et al 1998, Orzechowski et al 2002, and proliferation (Sigaud et al 2005) in a dose-and timedependent manner. In contrast with the wide belief that H 2 O 2 has only harmful functions due to its relentless production with a damaging nature, it has been shown that H 2 O 2 stimulates cell growth/proliferation and DNA synthesis in different types of cells, indicating that H 2 O 2 acts as an important signaling molecule (Rao & Berk 1992, Fiorani et al 1995.…”

Section: Discussionmentioning

confidence: 99%

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

Pronsato¹,

Boland²,

Milanesi³

2012

Journal of Endocrinology

View full text Add to dashboard Cite

Experimental data indicate that apoptosis is activated in the aged skeletal muscle, contributing to sarcopenia. We have previously demonstrated that testosterone protects against hydrogen peroxide (H 2 O 2 )-induced apoptosis in C2C12 muscle cells. Here we identified molecular events involved in the antiapoptotic effect of testosterone. At short times of exposure to H 2 O 2 cells exhibit a defense response but at longer treatment times cells undergo apoptosis. Incubation with testosterone prior to H 2 O 2 induces BAD inactivation, inhibition of poly(ADP-ribose) polymerase cleavage, and a decrease in BAX levels, and impedes the loss of mitochondrial membrane potential, suggesting that the hormone participates in the regulation of the apoptotic intrinsic pathway. Simultaneous treatment with testosterone, H 2 O 2 , and the androgen receptor (AR) antagonist, flutamide, reduces the effects of the hormone, pointing to a possible participation of the AR in the antiapoptotic effect. The data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.

show abstract

Section: Discussionmentioning

confidence: 99%

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

Pronsato¹,

Boland²,

Milanesi³

2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…2,3 Chronic treatment of C2C12 satellite cells with hydrogen peroxide (H 2 O 2 ) accelerated either the formation of myotubes or cell elimination. 4 DMSO, an antagonist of ROS action in muscle cells, can inhibit myogenesis in cultured C2C12 myoblasts. 5 Taken together, ROS play a very important role in myogenesis with partial leakage of electrons from mitochondrial cytochrome-c oxidase and transfer of electrons to oxygen, generating incompletely reduced oxygen species.…”

Section: Introductionmentioning

confidence: 95%

“…Both mitogenicity and anabolism are affected by H 2 O 2 ; H 2 O 2 directly influences myogenesis and muscle cell apoptosis. 7 Apoptosis-inducing factor (AIF) is a ubiquitous FAD-binding flavoprotein. During apoptotic induction, AIF is translocated from the mitochondrial intermembrane space to the nucleus, where it interacts with DNA and activates a nuclear endonuclease.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial AIF protein involved in skeletal muscle regeneration

Qiu

Lai

et al. 2008

Cell Biochemistry & Function

View full text Add to dashboard Cite

The mitochondrial flavoprotein apoptosis-inducing factor (AIF) has proved to be either the main mediator of apoptosis or an anti-apoptotic factor via its putative oxidoreductase and peroxide scavenging activities. We report here that 100 mM hydrogen peroxide (H 2 O 2 ) induced the proliferation of C2C12 myoblasts and over-expression of AIF simultaneously in vitro. Immunofluorescence showed that the over-expression of AIF was located in the cytoplasm. The immunopositive AIF was detected in nuclei 27 days after denervation of skeletal muscle, but in the cytoplasm it was detected 27 days after fiber-damaged skeletal muscle. AIF may be a factor involved in skeletal muscle regeneration.

show abstract

“…In muscle tissue, low doses have been reported to promote myogenesis and myotube formation, whereas high doses have an opposing effect via activation of the transcription factors in the NFκB-family and an upregulation of the proteins in the ubiquitin-proteasome pathway (2,3). High H 2 O 2 levels are known to be caused by increased levels of cytokines, as seen in chronic diseases, and glucocorticoid treatment and are also associated with muscle atrophy (2,(4)(5)(6). A third factor that has been proposed to mediate the control of muscle size is calcineurin, a serine/threonine phosphatase that is activated in response to increased intracellular levels of Ca 2+ .…”

Section: Introductionmentioning

confidence: 99%

Transcription Factors in Muscle Atrophy Caused by Blocked Neuromuscular Transmission and Muscle Unloading In Rats

Nordquist

Höglund

Norman

et al. 2007

Mol Med

View full text Add to dashboard Cite

The muscle wasting associated with long-term intensive care unit (ICU) treatment has a negative effect on muscle function resulting in prolonged periods of rehabilitation and a decreased quality of life. To identify mechanisms behind this form of muscle wasting, we have used a rat model designed to mimic the conditions in an ICU. Rats were pharmacologically paralyzed with a postsynaptic blocker of neuromuscular transmission, and mechanically ventilated for one to two weeks, thereby unloading the limb muscles. Transcription factors were analyzed for cellular localization and nuclear concentration in the fast-twitch muscle extensor digitorum longus (EDL) and in the slow-twitch soleus. Significant muscle wasting and upregulation of mRNA for the ubiquitin ligases MAFbx and MuRF1 followed the treatment. The IκB family-member Bcl-3 displayed a concomitant decrease in concentration, suggesting altered κB controlled gene expression, although NFκB p65 was not significantly affected. The nuclear levels of the glucocorticoid receptor (GR) and the thyroid receptor α1 (TRα1) were altered and also suggested as potential mediators of the MAFbx-and MuRF1-induction in the absence of induced Foxo1. We believe that this model, and the strategy of quantifying nuclear proteins, will provide a valuable tool for further, more detailed, analyses of the muscle wasting occurring in patients kept on a mechanical ventilator. variations in the response. For example, cachexia associated with disease states such as cancer and sepsis involves an increase in inflammatory cytokine production, which activates transcription factors that are, at least partly, distinct from those activated by disuse (12). How, and if, these differences affect the net result of the atrophic process is still unclear.Muscle wasting and impaired muscle function impose a risk to critically ill ICU patients during treatment. Specifically, neuromuscular abnormalities have been reported as the dominant cause for the reduced quality of life in critically ill ICU survivors, and are remaining even up to two years after hospital discharge (13,14). Therefore, our research is focused on the molecular events mediating the muscle atrophy in ICU patients, because successful treatment of this side effect would be highly beneficial for the survival, recovery, and quality of life in these patients. To address this issue, we have used an experimental rat model mimicking the conditions for many ICU patients, such as mechanical ventilation for long durations (weeks), postsynaptic block of neuromuscular transmission to facilitate ventilation, and unloading of muscles. In this study, the levels of a number of transcription factors in nuclear extracts from muscle tissue, and their spatial organization in the muscle fiber, have been investigated. The transcription factors we selected for investigation had been implicated in the expression of MAFbx and MuRF1 or as downstream effectors of signal transduction pathways previously linked to muscle atrophy or in the regulation of differentiation an...

show abstract

Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?

Cited by 28 publications

References 46 publications

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

Mitochondrial AIF protein involved in skeletal muscle regeneration

Transcription Factors in Muscle Atrophy Caused by Blocked Neuromuscular Transmission and Muscle Unloading In Rats

Contact Info

Product

Resources

About