| Autor: |
Mohammed, Zainab M., Subramanian, Veedamali S., Molina, Andres, Vaziri, Nosratola D., Said, Hamid M. |
| Předmět: |
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| Zdroj: |
FASEB Journal; Apr2007, Vol. 21 Issue 5, pA532-A533, 2p |
| Abstrakt: |
Thiamine is essential for the functions of all human tissues including the retina and Thiamine Responsive Megaloblastic Anemia (TRMA) is associated with retinal abnormality and visual disturbances. Human retinal pigment epithelial (hRPE) cells play a pivotal role in supplying thiamine to retina but nothing is known about the cell and molecular biology of the uptake process. We used the ARPE-19 cells as model and showed the thiamine uptake process to be energy-, temperature- and neutral/alkaline pH -dependent, Na+-independent, saturable at both the nanomolar and the micromolar concentrations ranges, specific for thiamine, and sensitive to sulfhydryl group inhibition. Amiloride and the antitrypanosomal drug melarsoprol inhibit thiamine uptake in other cells, but in ARPE-19 cells only amiloride was effective. The hTHTR-1 is expressed at a significantly higher level than that of the hTHTR-2 in ARPE-19 cells and in native human retina. Uptake of thiamine was adaptively regulated by extra-cellular substrate level via transcriptionally mediated mechanisms that involve both the hTHTR-1 and hTHTR-2; it was also regulated by an intracellular Ca2+/CaM -mediated pathway. Confocal imaging of living ARPE-19 cells expressing TRMA-associated hTHTR-1 mutants showed different expression phenotypes. These results demonstrate for the first time the existence of a specialized and regulated process for thiamine uptake in hRPE cells. Further, clinical mutations of the hTHTR-1 leads to impaired cell surface expression and/or its function. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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