ABSTRACT
This is the first case confirmed the association between PI development and nintedanib by the reproducibility of PI development. In patients taking a combination treatment with corticosteroid and nintedanib, clinicians should be careful regarding the development of PI although the patient improved only after discontinuation of nintedanib treatment.
ABSTRACT
Iron is an essential metal for all living organisms that is absorbed in the intestinal cells as a heme-chelated or free form. It is unclear how important plant-derived chelators, such as nicotianamine (NA), an organic small molecule that is ubiquitous in crops, vegetables, and various other foods, contribute to iron bioavailability in mammals. We performed electrophysiological assays with Xenopus laevis oocytes and radioactive tracer experiments with Caco-2 cells. The findings revealed that the proton-coupled amino acid transporter SLC36A1 (PAT1) transports iron in the form of NA-Fe (II) complex in vitro. Decreased expression of hPAT1 by RNA interference in Caco-2 cells reduced the uptake of NA-59Fe (II) complex. The uptake of inorganic 59Fe (II) was relatively unaffected. These results imply that PAT1 transports iron as a NA-Fe (II) complex. The rate of 59Fe absorption in the spleen, liver, and kidney was higher when mice were orally administered NA-59Fe (II) compared with free 59Fe (II). The profile of site-specific PAT1 expression in the mouse intestine coincided with those of NA and iron contents, which were the highest in the proximal jejunum. Orally administered NA-59Fe (II) complex in mice was detected in the proximal jejunum by thin layer chromatography. In contrast, much less 59Fe (or NA) was detected in the duodenum, where the divalent metal transporter SLC11A2 (DMT1) absorbs free Fe (II). The collective results revealed the role of PAT1 in NA-Fe (II) absorption in the intestine and potential implication of NA in iron uptake in mammals.
Subject(s)
Azetidinecarboxylic Acid/analogs & derivatives , Chelating Agents/pharmacology , Intestine, Small/drug effects , Intestine, Small/metabolism , Iron/metabolism , Animals , Azetidinecarboxylic Acid/pharmacology , Biological Availability , Biological Transport/drug effects , Cells, Cultured , Duodenum/drug effects , Duodenum/metabolism , Humans , Intestinal Absorption/drug effects , Jejunum/drug effects , Jejunum/metabolism , Male , Mice , Mice, Inbred ICR , Phytochemicals/pharmacology , Xenopus laevisABSTRACT
The expression of auxin-responsive genes is regulated by the TIR1/AFB auxin receptor-dependent degradation of Aux/IAA transcriptional repressors, which interact with auxin-responsive factors (ARFs). Most of the 29 Aux/IAA genes present in Arabidopsis have not been functionally characterized to date. IAA8 appears to have a distinct function from the other Aux/IAA genes, due to its unique transcriptional response to auxin and the stability of its encoded protein. In this study, we characterized the function of Arabidopsis IAA8 in various developmental processes governed by auxin and in the transcriptional regulation of the auxin response. Transgenic plants expressing estrogen-inducible IAA8 (XVE::IAA8) exhibited significantly fewer lateral roots than the wild type, and an IAA8 loss-of-function mutant exhibited significantly more. Ectopic overexpression of IAA8 resulted in abnormal gravitropism. The strong induction of early auxin-responsive marker genes by auxin treatment was delayed by IAA8 overexpression. GFP-fusion analysis revealed that IAA8 localized not only to the nucleus, but, in contrast to other Aux/IAAs, also to the cytosol. Furthermore, we demonstrated that IAA8 interacts with TIR1, in an auxin-dependent fashion, and with ARF proteins, both in yeast and in planta. Taken together, our results show that IAA8 is involved in lateral root formation, and that this process is regulated through the interaction with the TIR1 auxin receptor and ARF transcription factors in the nucleus.
