Polyamines, androgens, and skeletal muscle hypertrophy

Lee, Nicole K. L.; MacLean, Helen E.

doi:10.1002/jcp.22569

Cited by 60 publications

(61 citation statements)

References 90 publications

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“…The biosynthesis pathways for two polyamines, spermine and spermidine, may be affected by dietary lysine through regulating the expression of AMD1 , which encodes S -adenosylmethionine decarboxylase 1 (AdoMetDC), a key enzyme in the rate-limiting step of polyamine biosynthesis [29]. Although the potential mechanism by which polyamines regulate skeletal muscle hypertrophy and atrophy are still unclear, there is a strong association between polyamine levels and muscle mass [29,30].…”

Section: Discussionmentioning

confidence: 99%

A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

Wang

Feugang

Crenshaw

et al. 2017

IJMS

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Nine crossbred finishing barrows (body weight 94.4 ± 6.7 kg) randomly assigned to three dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient (4.30 g/kg), lysine-adequate (7.10 g/kg), or lysine-excess (9.80 g/kg) diet for five weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. Statistical ANOVA analysis of the microarray data showed that 674 transcripts were differentially expressed (at p ≤ 0.05 level); 60 out of 131 transcripts (at p ≤ 0.01 level) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to: (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA; (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA; (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA; and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to: (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA; and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA. Collectively, dietary lysine may function as a signaling molecule to regulate protein turnover and lipid metabolism in the skeletal muscle of finishing pigs.

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Section: Discussionmentioning

confidence: 99%

A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

Wang

Feugang

Crenshaw

et al. 2017

IJMS

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“…On the other hand, the effects of polyamines on muscle function have been much less studied and have focused mainly on smooth muscles, especially heart muscle cells. Anabolic agents have been shown to increase both skeletal muscle mass and polyamines levels, but a causal link between polyamines and muscle growth has not been investigated [41]. Of note, the initiation factor eIF5A, whose synthesis requires spermidine, increases skeletal muscle stem cell differentiation [42].…”

Section: Discussionmentioning

confidence: 99%

Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition

et al. 2014

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Spermidine is a natural polyamine involved in many important cellular functions, whose supplementation in food or water increases life span and stress resistance in several model organisms. In this work, we expand spermidine’s range of age-related beneficial effects by demonstrating that it is also able to improve locomotor performance in aged flies. Spermidine’s mechanism of action on aging has been primarily related to general protein hypoacetylation that subsequently induces autophagy. Here, we suggest that the molecular targets of spermidine also include lipid metabolism: Spermidine-fed flies contain more triglycerides and show altered fatty acid and phospholipid profiles. We further determine that most of these metabolic changes are regulated through autophagy. Collectively, our data suggests an additional and novel lipid-mediated mechanism of action for spermidine-induced autophagy.

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“…Polyamines (putrescine, spermidine, and spermine) play a crucial role in regulating gene expression, DNA and protein synthesis, and nucleic acid packaging, as well as cell proliferation and differentiation (38,58). Odc1 is essential for growth and development, as Odc1-null mouse embryos die at embryonic (E) day 5.5 (E5.5) (59).…”

mentioning

confidence: 99%

Ornithine decarboxylase is upregulated by the androgen receptor in skeletal muscle and regulates myoblast proliferation

Lee

Skinner

Zajac

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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The aim of this study is to determine if the Odc1 gene, which encodes ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is directly regulated by the androgen receptor (AR) in skeletal muscle myoblasts and if Odc1 regulates myoblast proliferation and differentiation. We previously showed that expression of Odc1 is decreased in muscle from AR knockout male mice. In this study, we show in vivo that Odc1 expression is also decreased >60% in muscle from male muscle-specific AR knockout mice. In normal muscle homeostasis, Odc1 expression is regulated by age and sex, reflecting testosterone levels, as muscle of adult male mice expresses high levels of Odc1 compared with age-matched females and younger males. In vitro, expression of Odc1 is 10- and 1.5-fold higher in proliferating mouse C(2)C(12) and human skeletal muscle myoblasts, respectively, than in differentiated myotubes. Dihydrotestosterone increases Odc1 levels 2.7- and 1.6-fold in skeletal muscle cell myoblasts after 12 and 24 h of treatment, respectively. Inhibition of ODC activity in C(2)C(12) myoblasts by α-difluoromethylornithine decreases myoblast number by 40% and 66% following 48 and 72 h of treatment, respectively. In contrast, overexpression of Odc1 in C(2)C(12) myoblasts results in a 27% increase in cell number vs. control when cells are grown under differentiation conditions for 96 h. This prolonged proliferation is associated with delayed differentiation, with reduced expression of the differentiation markers myogenin and Myf6 in Odc1-overexpressing cells. In conclusion, androgens act via the AR to upregulate Odc1 in skeletal muscle myoblasts, and Odc1 promotes myoblast proliferation and delays differentiation.

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Polyamines, androgens, and skeletal muscle hypertrophy

Cited by 60 publications

References 90 publications

A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition

Ornithine decarboxylase is upregulated by the androgen receptor in skeletal muscle and regulates myoblast proliferation

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