Lactate overload inhibits myogenic activity in C2C12 myotubes
Lactate (LA), an endogenous metabolite produced from pyruvate, can accumulate in skeletal muscle in certain conditions including major diseases, as well as during intensive exercise. Using differentiated C2C12 myotubes, we evaluated the early (1-h) and delayed (24-h) effects of LA (8 mM) on mechanis...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2019-03-01
|
| Series: | Open Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/biol-2019-0004 |
| _version_ | 1818597085012819968 |
|---|---|
| author | Oh Sarah Se-Jung Kim Sujin Moon Sohee Park Dong-Ho Kang Ju-Hee |
| author_facet | Oh Sarah Se-Jung Kim Sujin Moon Sohee Park Dong-Ho Kang Ju-Hee |
| author_sort | Oh Sarah Se-Jung |
| collection | DOAJ |
| description | Lactate (LA), an endogenous metabolite produced from pyruvate, can accumulate in skeletal muscle in certain conditions including major diseases, as well as during intensive exercise. Using differentiated C2C12 myotubes, we evaluated the early (1-h) and delayed (24-h) effects of LA (8 mM) on mechanisms involved in myogenesis or muscle atrophy, including 5'-adenosine monophosphate-activated protein kinase (AMPK)-mediated inhibition of protein synthesis through the mTOR/P70-S6K pathway, Akt-mediated inhibition of expression of the MAFbx atrophic factor by FOXO3a and expression of the myogenic transcription factors, MyoD, myogenin and myosin heavy chain. Although the early effects of LA overload were not significant on myogenic or atrophic mechanisms, LA treatment for 24 h significantly activated atrophic mechanisms but suppressed myogenesis in myotubes. In addition, LA overload for 24 h significantly suppressed the expression of Sirtuin 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Consistent with LA-induced activation of atrophic mechanisms, the diameter of C2C12 myotubes treated with LA for 24 h, but not for 1 h, was significantly lower than in control myotubes. Thus, a sustained, but not a transient, LA overload could induce muscle atrophy through the regulation of AMPK- and Akt-mediated pathways, although further in vivo studies are needed to confirm this. |
| first_indexed | 2024-12-16T11:42:11Z |
| format | Article |
| id | doaj.art-78e24ea3dafc46418e8881c8765f152e |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-12-16T11:42:11Z |
| publishDate | 2019-03-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj.art-78e24ea3dafc46418e8881c8765f152e2022-12-21T22:32:54ZengDe GruyterOpen Life Sciences2391-54122019-03-01141293710.1515/biol-2019-0004biol-2019-0004Lactate overload inhibits myogenic activity in C2C12 myotubesOh Sarah Se-Jung0Kim Sujin1Moon Sohee2Park Dong-Ho3Kang Ju-Hee4Korea International School, Pangyo, Republic of KoreaDepartment of Kinesiology, Inha UniversityIncheon, South KoreaDepartment of Pharmacology, Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon, Republic of KoreaDepartment of Kinesiology, Inha University, 100, Inha-Ro, Nam-gu, Incheon 22212, Republic of KoreaDepartment of Pharmacology and Medicinal Toxicology Research Center, Hypoxia-related Diseases Research Center, Inha University School of Medicine, Room 1015, 60th Anniversary Hall, 100, Inha-ro, Nam-gu, Incheon 22212, Republic of KoreaLactate (LA), an endogenous metabolite produced from pyruvate, can accumulate in skeletal muscle in certain conditions including major diseases, as well as during intensive exercise. Using differentiated C2C12 myotubes, we evaluated the early (1-h) and delayed (24-h) effects of LA (8 mM) on mechanisms involved in myogenesis or muscle atrophy, including 5'-adenosine monophosphate-activated protein kinase (AMPK)-mediated inhibition of protein synthesis through the mTOR/P70-S6K pathway, Akt-mediated inhibition of expression of the MAFbx atrophic factor by FOXO3a and expression of the myogenic transcription factors, MyoD, myogenin and myosin heavy chain. Although the early effects of LA overload were not significant on myogenic or atrophic mechanisms, LA treatment for 24 h significantly activated atrophic mechanisms but suppressed myogenesis in myotubes. In addition, LA overload for 24 h significantly suppressed the expression of Sirtuin 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Consistent with LA-induced activation of atrophic mechanisms, the diameter of C2C12 myotubes treated with LA for 24 h, but not for 1 h, was significantly lower than in control myotubes. Thus, a sustained, but not a transient, LA overload could induce muscle atrophy through the regulation of AMPK- and Akt-mediated pathways, although further in vivo studies are needed to confirm this.https://doi.org/10.1515/biol-2019-0004lactateskeletal musclemyogenesisaktampk |
| spellingShingle | Oh Sarah Se-Jung Kim Sujin Moon Sohee Park Dong-Ho Kang Ju-Hee Lactate overload inhibits myogenic activity in C2C12 myotubes Open Life Sciences lactate skeletal muscle myogenesis akt ampk |
| title | Lactate overload inhibits myogenic activity in C2C12 myotubes |
| title_full | Lactate overload inhibits myogenic activity in C2C12 myotubes |
| title_fullStr | Lactate overload inhibits myogenic activity in C2C12 myotubes |
| title_full_unstemmed | Lactate overload inhibits myogenic activity in C2C12 myotubes |
| title_short | Lactate overload inhibits myogenic activity in C2C12 myotubes |
| title_sort | lactate overload inhibits myogenic activity in c2c12 myotubes |
| topic | lactate skeletal muscle myogenesis akt ampk |
| url | https://doi.org/10.1515/biol-2019-0004 |
| work_keys_str_mv | AT ohsarahsejung lactateoverloadinhibitsmyogenicactivityinc2c12myotubes AT kimsujin lactateoverloadinhibitsmyogenicactivityinc2c12myotubes AT moonsohee lactateoverloadinhibitsmyogenicactivityinc2c12myotubes AT parkdongho lactateoverloadinhibitsmyogenicactivityinc2c12myotubes AT kangjuhee lactateoverloadinhibitsmyogenicactivityinc2c12myotubes |