Reactive oxygen species (ROS) are currently recognized as a key driver of several physiologicalprocesses. 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. PKCsplay a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and anup-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecularlink between redox homeostasis and myogenic differentiation. We used an in vitro model of amouse myoblast cell line (C2C12) to study the PKC–redox axis. We demonstrated that the transitionfrom 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 significantlyhigher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore,we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein contentwhile SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be anup-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interactswith Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate thatPKCe 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; Luisa Arcari, Maria; Micheloni, Cristina; Vitale, Marco; Gobbi, Giuliana; Mirandola, Prisco; Carubbi, Cecilia. - In: CELLS. - ISSN 2073-4409. - 12:13(2023), pp. 1-17. [10.3390/cells12131792]

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

Marco Vitale;
2023-01-01

Abstract

Reactive oxygen species (ROS) are currently recognized as a key driver of several physiologicalprocesses. 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. PKCsplay a tissue-specific role in redox biology, with specific isoforms being both a target of ROS and anup-stream regulator of ROS production. Therefore, we hypothesized that PKCe represents a molecularlink between redox homeostasis and myogenic differentiation. We used an in vitro model of amouse myoblast cell line (C2C12) to study the PKC–redox axis. We demonstrated that the transitionfrom 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 significantlyhigher in the late phases of myogenic differentiation, mimicking PKCe protein content. Furthermore,we demonstrated that PKCe inhibition increases ROS and reduces SOD2 protein contentwhile SOD2 silencing did not affect PKCe protein content, suggesting that the kinase could be anup-stream regulator of SOD2. To support this hypothesis, we found that in C2C12 cells, PKCe interactswith Nrf2, whose activation induces SOD2 transcription. Overall, our results indicate thatPKCe is capable of activating the antioxidant signaling preventing ROS accumulation in a myotube,eventually promoting myogenic differentiation.
2023
PKC epsilon
SOD2
antioxidant
reactive oxygen species
skeletal muscle
myogenesis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/153999
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