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Pharm Res
2019 Apr 17;366:84. doi: 10.1007/s11095-019-2626-3.
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Transport Mechanisms for the Nutritional Supplement β-Hydroxy-β-Methylbutyrate (HMB) in Mammalian Cells.
Ogura J
,
Sato T
,
Higuchi K
,
Bhutia YD
,
Babu E
,
Masuda M
,
Miyauchi S
,
Rueda R
,
Pereira SL
,
Ganapathy V
.
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PURPOSE: β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells.
METHODS: Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. As HMB is a monocarboxylate, focus was on monocarboxylate transporters, monitoring interaction of HMB with H+-coupled lactate uptake, and influence of H+ directly on HMB uptake. Involvement of MCT1-4 was studied using selective inhibitors and gene silencing. Involvement of human Na+/monocarboxylate transporter SMCT1 was also assessed using Xenopus oocytes.
RESULTS: H+-coupled lactate uptake was inhibited by HMB in both mammalian cells. HMB uptake was H+-coupled and inhibited by lactate. C2C12 cells expressed MCT1 and MCT4; MCF7 cells expressed MCT1-4; undifferentiated C2C12 cells expressed SMCT1. SMCT1 mediated Na+-coupled HMB transport. Inhibitors of MCT1/4, siRNA-mediated gene silencing, and expression pattern showed that MCT1-4 were responsible only for a small portion of HMB uptake in these cells.
CONCLUSION: HMB uptake in C2C12 and MCF7 cells is primarily H+-coupled and inhibited by lactate, but MCT1-4 are only partly responsible for HMB uptake. SMCT1 also transports HMB, but in a Na+-coupled manner. Other, yet unidentified, transporters mediate the major portion of HMB uptake in C2C12 and MCF7 cells.
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