Vitamin A deficiency and mutations of RXRalpha, RXRbeta and RARalpha lead to early differentiation of embryonic ventricular cardiomyocytes

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4749-4758 ◽  
Author(s):  
P. Kastner ◽  
N. Messaddeq ◽  
M. Mark ◽  
O. Wendling ◽  
J.M. Grondona ◽  
...  
Keyword(s):  
Vitamin A ◽  
Ventricular Myocytes ◽  
Cardiac Development ◽  
Vitamin A Deficiency ◽  
Wild Type ◽  
Knock Out ◽  
Support Cell ◽  
Ventricular Cardiomyocytes ◽  
And Control ◽  
Null Mutants

Knock-out of the mouse RXRalpha gene was previously shown to result in a hypoplastic heart ventricular wall, histologically detectable in 12.5 dpc fetuses. We show here that a precocious differentiation can be detected as early as 8.5 dpc in ventricular cardiomyocytes of RXRalpha(−/−) mutants. This precocious differentiation, which is characterized by the presence of striated myofibrils, sarcoplasmic reticulum and intercalated disks, is found after 9.5 dpc in about 50% of RXRalpha(−/−) subepicardial myocytes. In contrast, wild-type subepicardial myocytes remain morphologically undifferentiated up to at least 16.5 dpc. A similar precocious differentiation was observed in 9.5 dpc subepicardial myocytes of several RXRbeta(−/−) and RARalpha(−/−) mutants, as well as in vitamin A-deficient embryos. The proportion of differentiated subepicardial myocytes almost reached 100% in RXRalpha/RXRbeta double null mutants, indicating a partial functional redundancy between RXRalpha and RXRbeta. This differentiation defect was always paralleled by a decrease in the mitotic index. In addition, subepicardial myocytes of RXRalpha(−/−), RXRalpha(−/−)/RXRbeta(−/−) or vitamin A deficient, but not of RXRbeta(−/−) and RARalpha(−/−) embryos, were often flattened and more loosely connected to one another than those of WT embryos. Thus, retinoids are required at early stages of cardiac development to prevent differentiation, support cell proliferation and control the shape of ventricular myocytes, and both RXRs and RARs participate in the mediation of these functions.

Abstract 304: Global Transcriptional Effects of Vitamin A Deficiency on the Postnatal Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Cristi L Galindo ◽  
Truc-Linh Tran ◽  
Xuyang Peng ◽  
Douglas B Sawyer ◽  
Mary Asson-Batres
Keyword(s):  
Vitamin A ◽  
Natriuretic Peptide ◽  
Heart Development ◽  
Ventricular Remodeling ◽  
Vitamin A Deficiency ◽  
Healing Process ◽  
Mutant Mice ◽  
Wound Healing Process ◽  
Gene Encoding ◽  
Knock Out

Vitamin A (VA) is the chemical precursor of retinoic acid (RA), which is critical for embryonic development and for growth, immunity, metabolism, and cell differentiation in postnatal regenerating systems such as skin, sensory organs, and stem cell niches in the brain. VA is also essential for embryonic heart development, and we hypothesized that Vitamin A might exert an effect on the postnatal heart similar to what is observed for other tissues. Here, we report the global transcriptional profiles of wild-type (WT) mice fed a VA sufficient diet (VAS) compared with retinyl acyl transferase (LRAT) knock-out mice fed either a VAS or VA deficient (VAD) diet. Knockout of the LRAT gene alone was sufficient to induce differential expression of 576 genes relative to WT. Feeding LRAT mutant mice a VAD diet resulted in a change in the relative expression levels of 257 genes relative to LRAT mutant mice fed a VAS diet. As expected, we observed transcriptional alterations related to Vitamin A metabolism, including an increase in the gene encoding cellular retinoid binding protein 7 and down-regulation of the retinol metabolic enzymes Cy1a2 and Cyp2a4. Importantly, several cardiac genes not previously known to require VA were perturbed, including the gene encoding B-type natriuretic peptide, which was down-regulated in mutant mice irrespective of diet, and A-type natriuretic peptide, which was decreased only in mice fed the VAD diet. There was also a striking effect of VAD on genes important for immune responses, which could have an impact on the wound healing process subsequent to injury of the heart. This is consistent with recent evidence that showed that Vitamin A deficiency influences post-infarct ventricular remodeling in rats. In summary, this is the first microarray study of Vitamin A deficiency in the postnatal heart, which suggests mechanisms by which Vitamin A depletion may alter myocardial maintenance and repair after injury.

scholarly journals Assessment and Control of Vitamin A Deficiency: The Annecy Accords

2002 ◽  
Vol 132 (9) ◽  
pp. 2845S-2850S ◽  
Author(s):  
Alfred Sommer ◽  
Frances R. Davidson
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
And Control

scholarly journals Distribution of Vitamin-A Capsules for the Prevention and Control of Vitamin-A Deficiency in Bangladesh

1988 ◽  
Vol 10 (3) ◽  
pp. 1-12 ◽  
Author(s):  
I. Darnton-Hill ◽  
F. Sibanda ◽  
M. Mitra ◽  
M. M. Ali ◽  
A. E. Drexler ◽  
...  
Keyword(s):  
Vitamin A ◽  
Prevention And Control ◽  
Vitamin A Deficiency ◽  
And Control

New Issues in Developing Effective Approaches for the Prevention and Control of Vitamin A Deficiency

1998 ◽  
Vol 19 (2) ◽  
pp. 137-148 ◽  
Author(s):  
Martin W. Bloem ◽  
Saskia de Pee ◽  
Ian Darnton-Hill
Keyword(s):  
At Risk ◽  
Vitamin A ◽  
Prevention And Control ◽  
Control Strategies ◽  
Vitamin A Deficiency ◽  
Life Cycle Approach ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
To Come ◽  
And Control

Even mild to moderate vitamin A deficiency is now recognized as an important factor in child health and survival. This has given increased emphasis to the goal of virtually eliminating vitamin A deficiency and its consequences, including blindness, by the end of the decade. The implications of vitamin A deficiency, however, vary according to the group at risk, and this needs to be addressed when looking at ways to achieve the goal. In pre-school children, vitamin A deficiency can lead to increased risk of mortality and morbidity and to blindness. In pregnant and lactating women, it can lead to night-blindness and appears to have implications for maternal morbidity and mortality. Although the immediate health consequences for schoolchildren and adolescents are not completely known, they are probably less dramatic. Nevertheless, it is clear that there is a cross-generational cycle leading to and perpetuating vitamin A deficiency in affected communities. This also has implications when addressing prevention and control strategies. The existing, somewhat successful approach has been to target children aged six months to six years; it is implicit that this criterion is used to measure progress towards the end-of-decade goals. A broader, complementary, life-cycle approach to vitamin A deficiency is now appropriate in many countries. There is increasing emphasis on such approaches, i.e., fortifying foods with vitamin A and improving the diet, which address the whole population at risk. A mix of interventions will give governments the chance to shift from a subsidized vitamin A capsule programme to more sustainable, non-subsidized, consumer-funded vitamin A interventions, although in an appreciable number of countries, supplementation with vitamin A will be a necessity for some years to come. Guidelines to assist governments in such transitions are a high priority.

scholarly journals Major components in the KARRIKIN INSENSITIVE2-ligand signaling pathway are conserved in the liverwort, Marchantia polymorpha

2020 ◽  
Author(s):  
Yohei Mizuno ◽  
Aino Komatsu ◽  
Shota Shimazaki ◽  
Xiaonan Xie ◽  
Kimitsune Ishizaki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ubiquitin Ligase ◽  
Common Ancestor ◽  
Marchantia Polymorpha ◽  
Wild Type ◽  
Knock Out ◽  
Ubiquitin Ligase Complex ◽  
The Common ◽  
F Box Protein ◽  
And Control

AbstractKARRIKIN INSENSITIVE2 (KAI2) was first identified in Arabidopsis thaliana as a receptor of karrikin, a smoke-derived germination stimulant. KAI2 is also considered a receptor of an unidentified endogenous molecule called the KAI2-ligand (KL). Upon KAI2 activation, signals are transmitted through degradation of D53/SMXL proteins via ubiquitination by a Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. All components in the KL signaling pathway exist in the liverwort Marchantia polymorpha, namely MpKAI2A and MpKAI2B, MpMAX2 encoding the F-box protein, and MpSMXL, indicating that the signaling pathway became functional in the common ancestor of bryophytes and seed plants. Genetic analysis using knock-out mutants of these KL signaling genes, produced using the CRISPR system, indicated that MpKAI2A, MpMAX2 and MpSMXL act in the same genetic pathway and control early gemma growth. Introduction of MpSMXLd53, in which a domain required for degradation is mutated, into wild-type plants caused phenotypes resembling those of the Mpkai2a and Mpmax2 mutants. In addition, Citrine fluorescence was detected in tobacco cells transiently transformed with the 35S:MpSMXL-Citrine gene construct and treated with MG132, a proteasome inhibitor. On the other hand, introduction of 35S:MpSMXLd53-Citrine conferred Citrine fluorescence without MG132 treatment. These findings imply that MpSMXL is subjected to degradation, and that degradation of MpSMXL is crucial for KL signaling in M. polymorpha. We also showed that MpSMXL is negatively regulated by KL signaling. Taken together, this study demonstrates that basic mechanisms in the KL signaling pathway are conserved in M. polymorpha.

Retinal dysplasia and degeneration in RARbeta2/RARgamma2 compound mutant mice

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2173-2188 ◽  
Author(s):  
J.M. Grondona ◽  
P. Kastner ◽  
A. Gansmuller ◽  
D. Decimo ◽  
P. Chambon ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Retinal Pigment ◽  
Vitreous Body ◽  
Neural Retina ◽  
Mutant Mice ◽  
Retinol Binding Protein ◽  
Target Tissue ◽  
Retinal Dysplasia ◽  
Null Mutants

The eye is the organ whose development is the most frequently altered in response to maternal vitamin A deficiency [VAD; Warkany, J. and Schraffenberger, S. (1946). Archs Ophthalmol. 35, 150–169]. With the exception of prenatal retinal dysplasia, all the ocular abnormalities of the fetal VAD syndrome are recapitulated in mouse mutants lacking either RARalpha and RARbeta2, RARalpha and RARgamma, RARgamma and RARbeta2, or RXRalpha [Lohnes, D., Mark, M., Mendelsohn, C., Dolle, P., Dierich, A., Gorry, P., Gansmuller, A. and Chambon, P. (1994) Development 120, 2723–2748; Mendelsohn, C., Lohnes, D., Decimo, D., Lufkin, T., LeMeur, M., Chambon, P. and Mark, M. (1994) Development 120, 2749–2771; Kastner, P., Grondona, J. Mark, M., Gansmuller, A., LeMeur, M., Decimo, D., Vonesch, J.L., Dolle, P. and Chambon, P. (1994) Cell 78, 987–1003], thus demonstrating that retinoic acid (RA) is the active vitamin A metabolite during prenatal eye morphogenesis. Whether retinoids are also involved in postnatal eye development could not be investigated, as VAD newborns are not viable and the above RAR double null mutants and RXRalpha null mutants died in utero or at birth. We report here the generation of viable RARbeta2/RARgamma2 double null mutant mice, which exhibit several eye defects. The neural retina of newborn RARbeta2gamma2 mutants is thinner than normal due to a reduced rate of cell proliferation, and from day 4 shows multiple foci of disorganization of its layers. These RARbeta2gamma2 mutants represent the first genetically characterized model of retinal dysplasia and their phenotype demonstrates that RARs, and therefore RA, are required for retinal histogenesis. The RARbeta2gamma2 retinal pigment epithelium (RPE) cells display histological and/or ultrastructural alterations and/or fail to express cellular retinol binding protein I (CRBPI). Taken altogether, the early onset of the RPE histological defects and their striking colocalisation with areas of the neural retina displaying a faulty laminar organization, a reduced neuroblastic proliferation, and a lack of photoreceptor differentiation and/or increased apoptosis, make the RPE a likely target tissue of the RARbeta2gamma2 double null mutation. A degeneration of the adult neural retina, which may similarly be secondary to a defective RPE, is also observed in these mutants, thus demonstrating an essential role of RA in the survival of retinal cells. Moreover, all RARbeta2gamma2 mutants display defects in structures derived from the periocular mesenchyme including local agenesis of the choroid and of the sclera, small eyelids, and a persistence of the primary mesenchymal vitreous body. A majority of the RARbeta2 single null mutants also exhibit this latter defect, thus demonstrating that the RARbeta2 isoform plays a unique role in the formation of the definitive vitreous body.

scholarly journals Public Health Aspects in the Prevention and Control of Vitamin Deficiencies

2019 ◽  
Vol 3 (9) ◽  
Author(s):  
Ian Darnton-Hill
Keyword(s):  
Public Health ◽  
At Risk ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
The Elderly ◽  
Micronutrient Deficiencies ◽  
Middle Income ◽  
Vitamin Deficiencies ◽  
Populations At Risk ◽  
And Control

ABSTRACT Vitamin deficiencies remain major etiological factors in the global burden of disease, especially in low- and middle-income countries. The purpose of this state-of-the-art review was to update current information on deficiencies of vitamins and public health approaches to addressing them. Some stages of life present a higher risk of deficiency than others: risks are higher in pregnant women, children (from conception to young childhood), adolescents, the elderly, and all of the over 800 million people globally who are undernourished. At risk are approximately 125 million preschool children with vitamin A deficiency, as well as sub-populations at risk of deficiencies of folate, thiamin, vitamin B12, niacin, riboflavin, other B vitamins. and vitamin D. Addressing micronutrient deficiencies requires identifying those at risk and then working to prevent and manage that risk. Public health approaches include improved, diversified diets; supplementation; fortification and biofortification; and other supportive public health measures. Historically, as with pellagra and beriberi and, in the last 3 decades, with vitamin A and folic acid, there has been encouraging progress, but much remains to be done.

scholarly journals Dietary Intervention to Control Vitamin A Deficiency in Seven- to Twelve-Year-Old Children

1994 ◽  
Vol 15 (1) ◽  
pp. 1-4 ◽  
Author(s):  
A. Wadhwa ◽  
A. Singh ◽  
A. Mittal ◽  
S. Sharma
Keyword(s):  
Vitamin A ◽  
Nutrition Education ◽  
Dietary Intervention ◽  
Vitamin A Deficiency ◽  
Serum Vitamin ◽  
Intervention Period ◽  
Intervention Programme ◽  
Significant Difference ◽  
And Control ◽  
Β Carotene

The efficacy of a dietary intervention programme to control vitamin A deficiency through inexpensive, locally available sources of β-carotene was evaluated in 121 children 7–12 years old. The subjects were randomly divided into experimental and control groups. A three-day food intake was first recorded for each subject using a 24-hour recall method and repeated at the end of the study on a randomly selected subsample. The intervention period lasted one month, during which carrots, papayas, coriander, and mint were offered daily as sources of β-carotene. There was no significant difference in the dietary intakes of the groups before the study. After the intervention period, the serum vitamin A values of the experimental subjects were significantly higher than those of the controls. These results indicate that consumption of small amounts of inexpensive, readily available vegetable sources of β-carotene could help prevent and control vitamin A deficiency. Nutrition education programmes are needed to encourage the use of these foods for home consumption as well as in feeding programmes for schoolchildren.

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