scholarly journals Understanding the Complexity of Iron Sensing and Signaling Cascades in Plants

2019 ◽  
Vol 60 (7) ◽  
pp. 1440-1446 ◽  
Author(s):  
Takanori Kobayashi
Keyword(s):  
Iron Deficiency ◽  
Ubiquitin Ligases ◽  
Transcriptional Networks ◽  
Intracellular Iron ◽  
Long Distance ◽  
Environmental Signals ◽  
Helix Loop Helix ◽  
Iron Deficient ◽  
Wide Range ◽  
Graminaceous Plants

Abstract Under iron-deficient conditions, plants induce the expression of a set of genes involved in iron uptake and translocation. This response to iron deficiency is regulated by transcriptional networks mediated by transcription factors (TFs) and protein-level modification of key factors by ubiquitin ligases. Several of the basic helix–loop–helix TFs and the HRZ/BTS ubiquitin ligases are conserved across graminaceous and non-graminaceous plants. Other regulators are specific, such as IDEF1 and IDEF2 in graminaceous plants and FIT/FER and MYB10/72 in non-graminaceous plants. IMA/FEP peptides positively regulate the iron-deficiency responses in a wide range of plants by unknown mechanisms. Direct binding of iron or other metals to some key regulators, including HRZ/BTS and IDEF1, may be responsible for intracellular iron-sensing and -signaling events. In addition, key TFs such as FIT and IDEF1 interact with various proteins involved in signaling pathways of plant hormones, oxidative stress and metal abundance. Thus, FIT and IDEF1 might function as hubs for the integration of environmental signals to modulate the responses to iron deficiency. In addition to local iron signaling, root iron responses are modulated by shoot-derived long-distance signaling potentially mediated by phloem-mobile substances such as iron, iron chelates and IMA/FEP peptides.

scholarly journals Cloning and Characterization of Deoxymugineic Acid Synthase Genes from Graminaceous Plants

2006 ◽  
Vol 281 (43) ◽  
pp. 32395-32402 ◽  
Author(s):  
Khurram Bashir ◽  
Haruhiko Inoue ◽  
Seiji Nagasaka ◽  
Michiko Takahashi ◽  
Hiromi Nakanishi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Vascular Bundles ◽  
Long Distance ◽  
Mugineic Acid Family Phytosiderophores ◽  
Long Distance Transport ◽  
Shoot Tissue ◽  
Iron Deficient ◽  
Deoxymugineic Acid ◽  
Graminaceous Plants

Graminaceous plants have evolved a unique mechanism to acquire iron through the secretion of a family of small molecules, called mugineic acid family phytosiderophores (MAs). All MAs are synthesized from l-Met, sharing the same pathway from l-Met to 2′-deoxymugineic acid (DMA). DMA is synthesized through the reduction of a 3″-keto intermediate by deoxymugineic acid synthase (DMAS). We have isolated DMAS genes from rice (OsDMAS1), barley (HvDMAS1), wheat (TaD-MAS1), and maize (ZmDMAS1). Their nucleotide sequences indicate that OsDMAS1 encodes a predicted polypeptide of 318 amino acids, whereas the other three orthologs all encode predicted polypeptides of 314 amino acids and are highly homologous (82–97.5%) to each other. The DMAS proteins belong to the aldo-keto reductase superfamily 4 (AKR4) but do not fall within the existing subfamilies of AKR4 and appear to constitute a new subfamily within the AKR4 group. All of the proteins showed DMA synthesis activity in vitro. Their enzymatic activities were highest at pH 8–9, consistent with the hypothesis that DMA is synthesized in subcellular vesicles. Northern blot analysis revealed that the expression of each of the above DMAS genes is up-regulated under iron-deficient conditions in root tissue, and that of the genes OsDMAS1 and TaDMAS1 is up-regulated in shoot tissue. OsDMAS1 promoter-GUS analysis in iron-sufficient roots showed that its expression is restricted to cells participating in long distance transport and that it is highly up-regulated in the entire root under iron-deficient conditions. In shoot tissue, OsDMAS1 promoter drove expression in vascular bundles specifically under iron-deficient conditions.

scholarly journals OsbHLH058 and OsbHLH059 transcription factors positively regulate iron deficiency responses in rice

2019 ◽  
Vol 101 (4-5) ◽  
pp. 471-486 ◽  
Author(s):  
Takanori Kobayashi ◽  
Asami Ozu ◽  
Subaru Kobayashi ◽  
Gynheung An ◽  
Jong-Seong Jeon ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Iron Deficiency ◽  
Iron Uptake ◽  
Iron Concentration ◽  
Sufficient Conditions ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Iron Deficient ◽  
Inducible Genes

Abstract Key message Subgroup IVc basic helix-loop-helix transcription factors OsbHLH058 and OsbHLH059 positively regulate major iron deficiency responses in rice in a similar but distinct manner, putatively under partial control by OsHRZs. Abstract Under low iron availability, plants transcriptionally induce the expression of genes involved in iron uptake and translocation. OsHRZ1 and OsHRZ2 ubiquitin ligases negatively regulate this iron deficiency response in rice. The basic helix-loop-helix (bHLH) transcription factor OsbHLH060 interacts with OsHRZ1, and positively regulates iron deficiency-inducible genes. However, the functions of three other subgroup IVc bHLH transcription factors in rice, OsbHLH057, OsbHLH058, and OsbHLH059, have not yet been characterized. In the present study, we investigated the functions of OsbHLH058 and OsbHLH059 related to iron deficiency response. OsbHLH058 expression was repressed under iron deficiency, whereas the expression of OsbHLH057 and OsbHLH060 was moderately induced. Yeast two-hybrid analysis indicated that OsbHLH058 interacts with OsHRZ1 and OsHRZ2 more strongly than OsbHLH060, whereas OsbHLH059 showed no interaction. An in vitro ubiquitination assay detected no OsbHLH058 and OsbHLH060 ubiquitination by OsHRZ1 and OsHRZ2. Transgenic rice lines overexpressing OsbHLH058 showed tolerance for iron deficiency and higher iron concentration in seeds. These lines also showed enhanced expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron-sufficient conditions. Conversely, OsbHLH058 knockdown lines showed susceptibility to iron deficiency and reduced expression of many iron deficiency-inducible genes. OsbHLH059 knockdown lines were also susceptible to iron deficiency, and formed characteristic brownish regions in iron-deficient new leaves. OsbHLH059 knockdown lines also showed reduced expression of many iron deficiency-inducible genes. These results indicate that OsbHLH058 and OsbHLH059 positively regulate major iron deficiency responses in a similar but distinct manner, and that this function may be partially controlled by OsHRZs.

scholarly journals Menkes Copper ATPase (Atp7a) Is a Novel Metal-responsive Gene in Rat Duodenum, and Immunoreactive Protein Is Present on Brush-border and Basolateral Membrane Domains

2005 ◽  
Vol 280 (43) ◽  
pp. 36221-36227 ◽  
Author(s):  
Jennifer J. Ravia ◽  
Renu M. Stephen ◽  
Fayez K. Ghishan ◽  
James F. Collins
Keyword(s):  
Iron Deficiency ◽  
Brush Border ◽  
Iron Homeostasis ◽  
Polyclonal Antibodies ◽  
Basolateral Membrane ◽  
Copper Transport ◽  
Membrane Domains ◽  
Intracellular Iron ◽  
Iron Deficient

We previously noted strong induction of genes related to intestinal copper homeostasis (Menkes Copper ATPase (Atp7a) and metallothionein) in the duodenal epithelium of iron-deficient rats across several stages of postnatal development (Collins, J. F., Franck, C. A., Kowdley, K. V., and Ghishan, F. K. (2005) Am. J. Physiol., 288, G964–G971). We now report significant copper loading in the livers and intestines of iron-deficient rats. These findings are consistent with the hypothesis that there is increased intestinal copper transport during iron deficiency. We additionally found that hepatic Atp7b gene expression does not change with iron deficiency, suggesting that liver copper excretion is not altered. We have developed polyclonal antibodies against rat ATP7A, and we demonstrate the specificity of the immunogenic reaction. We show that the ATP7A protein is present on apical domains of duodenal enterocytes in control rats and on brush-border and basolateral membrane domains in iron-deprived rats. This localization is surprising, as previous in vitro studies have suggested that ATP7A traffics between the trans-Golgi network and the basolateral membrane. We further demonstrate that ATP7A protein levels are dramatically increased in brush-border and basolateral membrane vesicles isolated from iron-deficient rats. Other experiments show that iron refeeding partially corrects the hematological abnormalities seen in iron-deficient rats but that it does not ameliorate ATP7A protein induction, suggesting that Atp7a does not respond to intracellular iron levels. We conclude that ATP7A is involved in copper loading observed during iron deficiency and that increased intestinal copper transport is of physiological relevance, as copper plays important roles in overall body iron homeostasis.

scholarly journals Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

2021 ◽  
Vol 22 (4) ◽  
pp. 1539
Author(s):  
Paola De Sanctis ◽  
Giuseppe Filardo ◽  
Provvidenza Maria Abruzzo ◽  
Annalisa Astolfi ◽  
Alessandra Bolotta ◽  
...  
Keyword(s):  
Exercise Training ◽  
High Intensity ◽  
Vastus Lateralis ◽  
Mammalian Target Of Rapamycin ◽  
Differentially Expressed ◽  
Transcriptional Networks ◽  
Vastus Lateralis Muscle ◽  
Age Related ◽  
Wide Range ◽  
Non Coding Rnas

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

scholarly journals Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India

2017 ◽  
Vol 147 (12) ◽  
pp. 2297-2308 ◽  
Author(s):  
Michael J Wenger ◽  
Laura E Murray-Kolb ◽  
Julie EH Nevins ◽  
Sudha Venkatramanan ◽  
Gregory A Reinhart ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Status ◽  
Controlled Trial ◽  
Reproductive Age ◽  
Deficiency Anemia ◽  
Control Group ◽  
Attention And Memory ◽  
Double Blind ◽  
Iron Deficient ◽  
Mnemonic Function

Abstract Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory. Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function. Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18–55 y. Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function. Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

scholarly journals A Classification of Basic Helix-Loop-Helix Transcription Factors of Soybean

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Karen A. Hudson ◽  
Matthew E. Hudson
Keyword(s):  
Transcription Factors ◽  
Genome Sequence ◽  
Search Algorithm ◽  
Soybean Genome ◽  
Binding Potential ◽  
Future Research ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Wide Range

The complete genome sequence of soybean allows an unprecedented opportunity for the discovery of the genes controlling important traits. In particular, the potential functions of regulatory genes are a priority for analysis. The basic helix-loop-helix (bHLH) family of transcription factors is known to be involved in controlling a wide range of systems critical for crop adaptation and quality, including photosynthesis, light signalling, pigment biosynthesis, and seed pod development. Using a hidden Markov model search algorithm, 319 genes with basic helix-loop-helix transcription factor domains were identified within the soybean genome sequence. These were classified with respect to their predicted DNA binding potential, intron/exon structure, and the phylogeny of the bHLH domain. Evidence is presented that the vast majority (281) of these 319 soybean bHLH genes are expressed at the mRNA level. Of these soybean bHLH genes, 67% were found to exist in two or more homeologous copies. This dataset provides a framework for future studies on bHLH gene function in soybean. The challenge for future research remains to define functions for the bHLH factors encoded in the soybean genome, which may allow greater flexibility for genetic selection of growth and environmental adaptation in this widely grown crop.

Hypothermia in iron deficiency due to altered triiodothyronine metabolism

1980 ◽  
Vol 239 (5) ◽  
pp. R377-R381 ◽  
Author(s):  
E. Dillman ◽  
C. Gale ◽  
W. Green ◽  
D. G. Johnson ◽  
B. Mackler ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Iron Deficiency ◽  
Ambient Temperature ◽  
The Other ◽  
Other Hand ◽  
Iron Deficient ◽  
Catecholamine Response ◽  
Cutaneous Vasoconstriction

Iron-deficient rats become hypothermic and have an excessive catecholamine response when exposed to an ambient temperature of 4 degrees C. This is not due to changes in body insulation, since thickness is unaltered, since differences persist after removal of hair, and since cutaneous vasoconstriction is intact. On the other hand, oxygen consumption of iron-deficient animals at 4 degrees C is reduced, 39 +/- 3 ml . kg-1 . min-1 compared to 63 +/- 2 in control animals. Thyroxine (T4) values at 4 degrees C were 4.34 +/- 0.20 microgram/dl sera as compared to control values of 3.6 +/- 0.32. Triiodothyronine (T3) values of iron-deficient animals in the cold were 48 +/- 6.8 ng/dl as compared to 72 +/- 5.6 in control animals. Treatment of iron-deficient animals with iron was shown to normalize the plasma T3 response at 4 degrees C within 6 days. Thyroidectomized iron-deficient animals injected with T3 did not show hypothermia at 4 degrees C, whereas thyroidectomized iron-deficient animals injected with T4 showed hypothermia, increased catecholamines, and decreased T3 levels as compared to non-iron-deficient animals similarly treated. It is proposed that iron deficiency impairs conversion of T4 to T3 and that this is primarily responsible for the hypothermia observed.

Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure

2021 ◽  
pp. 1-8
Author(s):  
Kriti Puri ◽  
Joseph A. Spinner ◽  
Jacquelyn M. Powers ◽  
Susan W. Denfield ◽  
Hari P. Tunuguntla ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Deficiency ◽  
Transferrin Saturation ◽  
Systolic Heart Failure ◽  
Oral Iron ◽  
Wilcoxon Test ◽  
Iron Therapy ◽  
Oral Iron Therapy ◽  
Iron Deficient ◽  
Iron Replacement

Abstract Introduction: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. Methods: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. Results: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. Conclusions: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

Developmental iron deficiency dysregulates TET activity and DNA hydroxymethylation in the rat hippocampus and cerebellum

2022 ◽  
Author(s):  
Amanda K. Barks ◽  
Montana M. Beeson ◽  
Timothy C. Hallstrom ◽  
Michael K. Georgieff ◽  
Phu V. Tran
Keyword(s):  
Iron Deficiency ◽  
Neural Circuit ◽  
Epigenetic Modification ◽  
Rat Hippocampus ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Dna Hydroxymethylation ◽  
Iron Treatment ◽  
Iron Deficient ◽  
Increased Risk

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.

Lactate is essential for maintenance of euglycemia in iron-deficient rats at rest and during exercise

1993 ◽  
Vol 264 (4) ◽  
pp. E662-E667 ◽  
Author(s):  
J. K. Linderman ◽  
P. R. Dallman ◽  
R. E. Rodriguez ◽  
G. A. Brooks
Keyword(s):  
Iron Deficiency ◽  
Hemoglobin Concentration ◽  
Liver Glycogen ◽  
Beta Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Iron Deficient ◽  
Ici 118,551 ◽  
Beta 2 ◽  
Exercise Induced

To evaluate the hypothesis that lactate supply is essential to maintain euglycemia during iron deficiency, female Sprague-Dawley rats were assigned to iron-sufficient (50 mg Fe2+/kg diet, +Fe), or iron-deficient (15 mg Fe2+/kg diet, -Fe) dietary groups and were injected with a specific beta 2-adrenergic inhibitor, ICI 118,551 (1.0 mg/kg body wt). Rats were studied at rest or after 30 min of running at 13.4 m/min 0% grade. Dietary iron deficiency decreased hemoglobin concentration 38%, but resting arterial concentrations of glucose ([Glc]), lactate ([La]), or alanine ([Ala]) were unaffected. Administration of ICI 118,551 (beta 2-blockade) decreased [La] and [Glc] 52 and 32% in resting -Fe rats, respectively. beta 2-Blockade attenuated the exercise-induced rise in [La] and decreased [Glc] 31% in exercising -Fe rats. [Ala] were unaffected by iron deficiency or exercise but decreased 24 and 18% because of beta 2-blockade in resting and exercising +Fe rats. Iron deficiency depleted resting liver glycogen concentration 45%, with no additional effect of exercise or beta 2-blockade. beta-Blockade decreased arterial insulin and increased arterial glucagon concentrations in resting -Fe and +Fe rats. During exercise glucagon concentration increased significantly more in -Fe than +Fe rats. Decreased arterial [La] with a corresponding decrease in arterial [Glc] in response to beta 2-blockade support the contention that lactate supply is critical to maintenance of euglycemia in -Fe rats at rest and during exercise.

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