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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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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. |
format | Online Article Text |
id | pubmed-10616405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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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