Abstract
High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and thioredoxin. HMGB1, a protein thiol, weakly expressed in healthy muscles, increases during regeneration in parallel with the antioxidant response in both fibers and leukocytes. A reduced environment may be important to maintain HMGB1 bioactivity. Indeed, oxidation abrogates both muscle stem cell migration in response to HMGB1 and their ability to differentiate into myofibers in vitro. We propose that the early antioxidant response in regenerating muscle limits HMGB1 oxidation, thus allowing successful muscle regeneration.
| Original language | English |
|---|---|
| Pages (from-to) | 2161-2174 |
| Number of pages | 14 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 15 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Oct 15 2011 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Physiology
- Clinical Biochemistry
Cite this
High-mobility group box 1 release and redox regulation accompany regeneration and remodeling of skeletal muscle. / Vezzoli, Michela; Castellani, Patrizia; Corna, Gianfranca; Castiglioni, Alessandra; Bosurgi, Lidia; Monno, Antonella; Brunelli, Silvia; Manfredi, Angelo A.; Rubartelli, Anna; Rovere-Querini, Patrizia.
In: Antioxidants and Redox Signaling, Vol. 15, No. 8, 15.10.2011, p. 2161-2174.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High-mobility group box 1 release and redox regulation accompany regeneration and remodeling of skeletal muscle
AU - Vezzoli, Michela
AU - Castellani, Patrizia
AU - Corna, Gianfranca
AU - Castiglioni, Alessandra
AU - Bosurgi, Lidia
AU - Monno, Antonella
AU - Brunelli, Silvia
AU - Manfredi, Angelo A.
AU - Rubartelli, Anna
AU - Rovere-Querini, Patrizia
PY - 2011/10/15
Y1 - 2011/10/15
N2 - High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and thioredoxin. HMGB1, a protein thiol, weakly expressed in healthy muscles, increases during regeneration in parallel with the antioxidant response in both fibers and leukocytes. A reduced environment may be important to maintain HMGB1 bioactivity. Indeed, oxidation abrogates both muscle stem cell migration in response to HMGB1 and their ability to differentiate into myofibers in vitro. We propose that the early antioxidant response in regenerating muscle limits HMGB1 oxidation, thus allowing successful muscle regeneration.
AB - High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and thioredoxin. HMGB1, a protein thiol, weakly expressed in healthy muscles, increases during regeneration in parallel with the antioxidant response in both fibers and leukocytes. A reduced environment may be important to maintain HMGB1 bioactivity. Indeed, oxidation abrogates both muscle stem cell migration in response to HMGB1 and their ability to differentiate into myofibers in vitro. We propose that the early antioxidant response in regenerating muscle limits HMGB1 oxidation, thus allowing successful muscle regeneration.
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UR - http://www.scopus.com/inward/citedby.url?scp=80052563357&partnerID=8YFLogxK
U2 - 10.1089/ars.2010.3341
DO - 10.1089/ars.2010.3341
M3 - Article
C2 - 21294652
AN - SCOPUS:80052563357
VL - 15
SP - 2161
EP - 2174
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 8
ER -