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Protein characterization of NA+-independent system L amino acid transporter 3 in mice: a potential role in supply of branched-chain amino acids under nutrient starvation.

ABSTRACT: We recently cloned the human Na(+)-independent system L neutral amino acid transporter LAT3. The aim of the present study was to characterize the molecular nature of mouse LAT3 at the protein level. Isolated mouse LAT3 showed 83% identity to human LAT3. Xenopus oocytes injected with mouse LAT3 cRNA showed the same functional property as human LAT3. Reverse transcriptase-polymerase chain reaction revealed apparent transcripts of mouse LAT3 in the liver, skeletal muscle, and pancreas, an expression pattern identical to that found in humans. Antibody generated against mouse LAT3 detected both approximately 58-kd and 48-kd bands in the sample from liver and only a 48-kd band in skeletal muscle and pancreas. Immunohistochemical study showed its clear localization in the plasma membrane of liver and skeletal muscle, whereas it was only detectable in the endoplasmic reticulum and in crystalline inclusions in pancreatic acinar cells. Starvation induced up-regulation of mouse LAT3 protein and mRNA in both liver and skeletal muscle but not in pancreas. These results suggest that LAT3 may indeed function as an amino acid transporter, transporting branched-chain amino acids from liver and skeletal muscle to the bloodstream and thereby participating in the regulatory system of interorgan amino acid nutrition.

SUBMITTER: Fukuhara D

PROVIDER: S-EPMC1864869 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Protein characterization of NA+-independent system L amino acid transporter 3 in mice: a potential role in supply of branched-chain amino acids under nutrient starvation.

Fukuhara Daisuke D Kanai Yoshikatsu Y Chairoungdua Arthit A Babu Ellappan E Bessho Fumio F Kawano Toshio T Akimoto Yoshihiro Y Endou Hitoshi H Yan Kunimasa K

The American journal of pathology 20070301 3

We recently cloned the human Na(+)-independent system L neutral amino acid transporter LAT3. The aim of the present study was to characterize the molecular nature of mouse LAT3 at the protein level. Isolated mouse LAT3 showed 83% identity to human LAT3. Xenopus oocytes injected with mouse LAT3 cRNA showed the same functional property as human LAT3. Reverse transcriptase-polymerase chain reaction revealed apparent transcripts of mouse LAT3 in the liver, skeletal muscle, and pancreas, an expressio ...[more]

PMID: 17322374

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Project description:BackgroundCirculating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear.MethodsWe evaluated circulating BCAA levels and breast cancer risk within the Nurses' Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women's Health Study (WHS). All statistical tests were 2-sided.ResultsAmong NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, P trend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, P trend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, P trend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, P trend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, P trend = .04).ConclusionsNo statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.

Dataset Information

Protein characterization of NA+-independent system L amino acid transporter 3 in mice: a potential role in supply of branched-chain amino acids under nutrient starvation.

Publications

Protein characterization of NA+-independent system L amino acid transporter 3 in mice: a potential role in supply of branched-chain amino acids under nutrient starvation.

Similar Datasets

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