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Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina

It is known that metabolic defects in the retinal pigment epithelium (RPE) can cause degeneration of its neighboring photoreceptors in the retina, leading to retinal degenerative diseases such as age-related macular degeneration. However, how RPE metabolism supports the health of the neural retina r...

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Autores principales: Zhu, Siyan, Xu, Rong, Engel, Abbi L., Wang, Yekai, McNeel, Rachel, Hurley, James B., Chao, Jennifer R., Du, Jianhai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616405/
https://www.ncbi.nlm.nih.gov/pubmed/37741457
http://dx.doi.org/10.1016/j.jbc.2023.105275
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author Zhu, Siyan
Xu, Rong
Engel, Abbi L.
Wang, Yekai
McNeel, Rachel
Hurley, James B.
Chao, Jennifer R.
Du, Jianhai
author_facet Zhu, Siyan
Xu, Rong
Engel, Abbi L.
Wang, Yekai
McNeel, Rachel
Hurley, James B.
Chao, Jennifer R.
Du, Jianhai
author_sort Zhu, Siyan
collection PubMed
description It is known that metabolic defects in the retinal pigment epithelium (RPE) can cause degeneration of its neighboring photoreceptors in the retina, leading to retinal degenerative diseases such as age-related macular degeneration. However, how RPE metabolism supports the health of the neural retina remains unclear. The retina requires exogenous nitrogen sources for protein synthesis, neurotransmission, and energy metabolism. Using (15)N tracing coupled with mass spectrometry, we found human RPE can utilize the nitrogen in proline to produce and export 13 amino acids, including glutamate, aspartate, glutamine, alanine, and serine. Similarly, we found this proline nitrogen utilization in the mouse RPE/choroid but not in the neural retina of explant cultures. Coculture of human RPE with the retina showed that the retina can take up the amino acids, especially glutamate, aspartate, and glutamine, generated from proline nitrogen in the RPE. Intravenous delivery of (15)N proline in vivo demonstrated (15)N-derived amino acids appear earlier in the RPE before the retina. We also found proline dehydrogenase, the key enzyme in proline catabolism is highly enriched in the RPE but not the retina. The deletion of proline dehydrogenase blocks proline nitrogen utilization in RPE and the import of proline nitrogen–derived amino acids in the retina. Our findings highlight the importance of RPE metabolism in supporting nitrogen sources for the retina, providing insight into understanding the mechanisms of the retinal metabolic ecosystem and RPE-initiated retinal degenerative diseases.
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spelling pubmed-106164052023-11-01 Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina Zhu, Siyan Xu, Rong Engel, Abbi L. Wang, Yekai McNeel, Rachel Hurley, James B. Chao, Jennifer R. Du, Jianhai J Biol Chem Research Article It is known that metabolic defects in the retinal pigment epithelium (RPE) can cause degeneration of its neighboring photoreceptors in the retina, leading to retinal degenerative diseases such as age-related macular degeneration. However, how RPE metabolism supports the health of the neural retina remains unclear. The retina requires exogenous nitrogen sources for protein synthesis, neurotransmission, and energy metabolism. Using (15)N tracing coupled with mass spectrometry, we found human RPE can utilize the nitrogen in proline to produce and export 13 amino acids, including glutamate, aspartate, glutamine, alanine, and serine. Similarly, we found this proline nitrogen utilization in the mouse RPE/choroid but not in the neural retina of explant cultures. Coculture of human RPE with the retina showed that the retina can take up the amino acids, especially glutamate, aspartate, and glutamine, generated from proline nitrogen in the RPE. Intravenous delivery of (15)N proline in vivo demonstrated (15)N-derived amino acids appear earlier in the RPE before the retina. We also found proline dehydrogenase, the key enzyme in proline catabolism is highly enriched in the RPE but not the retina. The deletion of proline dehydrogenase blocks proline nitrogen utilization in RPE and the import of proline nitrogen–derived amino acids in the retina. Our findings highlight the importance of RPE metabolism in supporting nitrogen sources for the retina, providing insight into understanding the mechanisms of the retinal metabolic ecosystem and RPE-initiated retinal degenerative diseases. American Society for Biochemistry and Molecular Biology 2023-09-21 /pmc/articles/PMC10616405/ /pubmed/37741457 http://dx.doi.org/10.1016/j.jbc.2023.105275 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Zhu, Siyan
Xu, Rong
Engel, Abbi L.
Wang, Yekai
McNeel, Rachel
Hurley, James B.
Chao, Jennifer R.
Du, Jianhai
Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title_full Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title_fullStr Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title_full_unstemmed Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title_short Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
title_sort proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616405/
https://www.ncbi.nlm.nih.gov/pubmed/37741457
http://dx.doi.org/10.1016/j.jbc.2023.105275
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