α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced...
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2021-07-01
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author | Koichiro Sumi Misato Sakuda Kinuyo Munakata Kentaro Nakamura Kinya Ashida |
author_facet | Koichiro Sumi Misato Sakuda Kinuyo Munakata Kentaro Nakamura Kinya Ashida |
author_sort | Koichiro Sumi |
collection | DOAJ |
description | There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions. |
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spelling | doaj.art-735ace407a83444f893e1ea80416d63e2023-11-22T04:36:47ZengMDPI AGNutrients2072-66432021-07-01137239110.3390/nu13072391α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 MyotubeKoichiro Sumi0Misato Sakuda1Kinuyo Munakata2Kentaro Nakamura3Kinya Ashida4Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanThere is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.https://www.mdpi.com/2072-6643/13/7/2391α-hydroxyisocaproic acidTNFαInterferon-γAMPKERKprotein synthesis |
spellingShingle | Koichiro Sumi Misato Sakuda Kinuyo Munakata Kentaro Nakamura Kinya Ashida α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube Nutrients α-hydroxyisocaproic acid TNFα Interferon-γ AMPK ERK protein synthesis |
title | α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube |
title_full | α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube |
title_fullStr | α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube |
title_full_unstemmed | α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube |
title_short | α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube |
title_sort | α hydroxyisocaproic acid decreases protein synthesis but attenuates tnfα ifnγ co exposure induced protein degradation and myotube atrophy via suppression of inos and il 6 in murine c2c12 myotube |
topic | α-hydroxyisocaproic acid TNFα Interferon-γ AMPK ERK protein synthesis |
url | https://www.mdpi.com/2072-6643/13/7/2391 |
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