Abstract
Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with 13C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids. Besides being oxidized through the Krebs cycle, proline is used to make citrate via reductive carboxylation. Citrate, made either from 13C proline or from 13C glucose, is preferentially exported to the apical side and is taken up by the retina. In conclusion, RPE cells consume multiple nutrients, including glucose and taurine, but prefer proline, and they actively synthesize and export metabolic intermediates to the apical side to nourish the outer retina.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12895-12905 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 292 |
| Issue number | 31 |
| DOIs | |
| State | Published - Jan 1 2017 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side. / Chao, Jennifer R.; Knight, Kaitlen; Engel, Abbi L.; Jankowski, Connor; Wang, Yekai; Manson, Megan A.; Gu, Haiwei; Djukovic, Danijel; Raftery, Daniel; Hurley, James B.; Du, Jianhai.
In: Journal of Biological Chemistry, Vol. 292, No. 31, 01.01.2017, p. 12895-12905.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human retinal pigment epithelial cells prefer proline as a nutrient and transport metabolic intermediates to the retinal side
AU - Chao, Jennifer R.
AU - Knight, Kaitlen
AU - Engel, Abbi L.
AU - Jankowski, Connor
AU - Wang, Yekai
AU - Manson, Megan A.
AU - Gu, Haiwei
AU - Djukovic, Danijel
AU - Raftery, Daniel
AU - Hurley, James B.
AU - Du, Jianhai
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with 13C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids. Besides being oxidized through the Krebs cycle, proline is used to make citrate via reductive carboxylation. Citrate, made either from 13C proline or from 13C glucose, is preferentially exported to the apical side and is taken up by the retina. In conclusion, RPE cells consume multiple nutrients, including glucose and taurine, but prefer proline, and they actively synthesize and export metabolic intermediates to the apical side to nourish the outer retina.
AB - Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with 13C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids. Besides being oxidized through the Krebs cycle, proline is used to make citrate via reductive carboxylation. Citrate, made either from 13C proline or from 13C glucose, is preferentially exported to the apical side and is taken up by the retina. In conclusion, RPE cells consume multiple nutrients, including glucose and taurine, but prefer proline, and they actively synthesize and export metabolic intermediates to the apical side to nourish the outer retina.
UR - http://www.scopus.com/inward/record.url?scp=85026743271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026743271&partnerID=8YFLogxK
U2 - 10.1074/jbc.M117.788422
DO - 10.1074/jbc.M117.788422
M3 - Article
VL - 292
SP - 12895
EP - 12905
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 31
ER -