Reactive oxygen species (ROS) are currently recognized as a key driver of several physiological processes. Increasing evidence indicates that ROS levels can affect myogenic differentiation, but the molecular mechanisms still need to be elucidated. Protein kinase C (PKC) epsilon (PKCe) promotes muscle stem cell differentiation and regeneration of skeletal muscle after injury. PKCs play a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and an up-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecular link between redox homeostasis and myogenic differentiation. We used an in vitro model of a mouse myoblast cell line (C2C12) to study the PKC–redox axis. We demonstrated that the transition from a myoblast to myotube is typified by increased PKCe protein content and decreased ROS. Intriguingly, the expression of the antioxidant enzyme superoxide dismutase 2 (SOD2) is significantly higher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore, we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein content while SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be an up-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interacts with Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate that PKCe is capable of activating the antioxidant signaling preventing ROS accumulation in a myotube, eventually promoting myogenic differentiation.

Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation / Pozzi, Giulia; Presta, Valentina; Masselli, Elena; Condello, Giancarlo; Cortellazzi, Samuele; Arcari, Maria Luisa; Micheloni, Cristina; Vitale, Marco; Gobbi, Giuliana; Mirandola, Prisco; Carubbi, Cecilia. - In: CELLS. - ISSN 2073-4409. - 12:792(2023), pp. 1-17.

Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation

Giulia Pozzi;Valentina Presta;Elena Masselli;Giancarlo Condello;Maria Luisa Arcari;Cristina Micheloni;Marco Vitale;Giuliana Gobbi
;
Prisco Mirandola
;
Cecilia Carubbi
2023-01-01

Abstract

Reactive oxygen species (ROS) are currently recognized as a key driver of several physiological processes. Increasing evidence indicates that ROS levels can affect myogenic differentiation, but the molecular mechanisms still need to be elucidated. Protein kinase C (PKC) epsilon (PKCe) promotes muscle stem cell differentiation and regeneration of skeletal muscle after injury. PKCs play a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and an up-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecular link between redox homeostasis and myogenic differentiation. We used an in vitro model of a mouse myoblast cell line (C2C12) to study the PKC–redox axis. We demonstrated that the transition from a myoblast to myotube is typified by increased PKCe protein content and decreased ROS. Intriguingly, the expression of the antioxidant enzyme superoxide dismutase 2 (SOD2) is significantly higher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore, we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein content while SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be an up-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interacts with Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate that PKCe is capable of activating the antioxidant signaling preventing ROS accumulation in a myotube, eventually promoting myogenic differentiation.
2023
Interplay between Protein Kinase C Epsilon and Reactive Oxygen Species during Myogenic Differentiation / Pozzi, Giulia; Presta, Valentina; Masselli, Elena; Condello, Giancarlo; Cortellazzi, Samuele; Arcari, Maria Luisa; Micheloni, Cristina; Vitale, Marco; Gobbi, Giuliana; Mirandola, Prisco; Carubbi, Cecilia. - In: CELLS. - ISSN 2073-4409. - 12:792(2023), pp. 1-17.
File in questo prodotto:
File Dimensione Formato  
cells-12-01792.pdf

accesso aperto

Tipologia: Versione (PDF) editoriale
Licenza: Creative commons
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2950752
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact