Abstract：
:Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7, which encodes for the y+LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse (Slc7a7-/-). The Slc7a7-/- model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7-/- mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7-/- model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Bodoy S,Sotillo F,Espino-Guarch M,Sperandeo MP,Ormazabal A,Zorzano A,Sebastio G,Artuch R,Palacín Mdoi
10.3390/ijms20215294subject
Has Abstractpub_date
2019-10-24 00:00:00issue
21issn
1422-0067pii
ijms20215294journal_volume
20pub_type
杂志文章abstract：:Caspase-8 was originally identified as a central player of programmed cell death triggered by death receptor stimulation. In that context, its activity is tightly regulated through several mechanisms, with the best established being the expression of FLICE-like inhibitory protein (FLIP) family proteins and the Src-dep...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19123798
更新日期：2018-11-29 00:00:00
abstract：:Fresh produce is often a source of enterohaemorrhagic Escherichia coli (EHEC) outbreaks. Fimbriae are extracellular structures involved in cell-to-cell attachment and surface colonisation. F9 (Fml) fimbriae have been shown to be expressed at temperatures lower than 37 °C, implying a function beyond the mammalian host....
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21249720
更新日期：2020-12-19 00:00:00
abstract：:Histone deacetylases have been a target of therapy for organ fibrosis. Here, we report the protective effect of CG200745 (CG), a novel histone deacetylase inhibitor, on tubulointerstitial fibrosis in Col4a3-/- mice, a murine model of Alport syndrome. Morphological analyses revealed CG treatment markedly alleviated kid...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21041473
更新日期：2020-02-21 00:00:00
abstract：:Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19030895
更新日期：2018-03-17 00:00:00
abstract：:Neurodegenerative diseases are characterized by adverse cellular environments and pathological alterations causing neurodegeneration in distinct brain regions. This development is triggered or facilitated by conditions such as hypoxia, ischemia or inflammation and is associated with disruptions of fundamental cellular...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms22020582
更新日期：2021-01-08 00:00:00
abstract：:The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into fou...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21155336
更新日期：2020-07-27 00:00:00
abstract：:Salinity is one of the most important abiotic stresses threatening plant growth and agricultural productivity worldwide. In green alga Chlamydomonas reinhardtii, physiological evidence indicates that saline stress increases intracellular peroxide levels and inhibits photosynthetic-electron flow. However, understanding...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19113359
更新日期：2018-10-26 00:00:00
abstract：:ATP is a major energy source in the mammalian cells, but it is an extracellular chemical messenger acting on P2 purinergic receptors. A line of evidence has shown that ATP is released from many different types of cells including neurons, endothelial cells, and muscle cells. In this review, we described the distributio...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms22010251
更新日期：2020-12-29 00:00:00
abstract：:The brain comprises a complex system of neurons interconnected by an intricate network of anatomical links. While recent studies demonstrated the correlation between anatomical connectivity patterns and gene expression of neurons, using transcriptomic information to automatically predict such patterns is still an open...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20082035
更新日期：2019-04-25 00:00:00
abstract：:In this study, caviar (sturgeon eggs) was used to elucidate its roles in adiponectin production and skin anti-aging. Recently, caviar has been largely used not only as a nutritional food, but also in cosmetic products. In particular, it has been reported that docosahexaenoic acid (DHA), as one of the main phospholipid...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21093383
更新日期：2020-05-11 00:00:00
abstract：:Wounds are a largely unrecognized, spiraling epidemic that affect millions of people world-wide [...]. ...
journal_title：International journal of molecular sciences
pub_type： 社论
doi：10.3390/ijms20071724
更新日期：2019-04-08 00:00:00
abstract：:Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20133135
更新日期：2019-06-27 00:00:00
abstract：:There have been no major improvements in the overall survival of ovarian cancer patients in recent decades. Even though more accurate surgery and more effective treatments are available, the mortality rate remains high. Given the differences in origin and the heterogeneity of these tumors, research to elucidate the si...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18081658
更新日期：2017-07-30 00:00:00
abstract：:Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differe...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21249400
更新日期：2020-12-10 00:00:00
abstract：:Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known abou...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17091501
更新日期：2016-09-08 00:00:00
abstract：:Many systems, including polymers and molecular liquids, when adequately cooled and/or compressed, solidify into a disordered solid, i.e., a glass. The transition is not abrupt, featuring progressive decrease of the microscopic mobility and huge slowing down of the relaxation. A distinctive aspect of glass-forming mate...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20225708
更新日期：2019-11-14 00:00:00
abstract：:EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-m...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms151119444
更新日期：2014-10-27 00:00:00
abstract：:Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6+ interleukin (IL)-17A-producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated in the Koebner pheno...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21020434
更新日期：2020-01-09 00:00:00
abstract：:Elderly and patients affected by chronic diseases face a high risk of muscle loss and impaired physical function. Omega 3 fatty acids (FA) attenuate inflammation and age-associated muscle loss, prevent systemic insulin resistance and improve plasma lipids, potentially impacting on sarcopenia. This paper aims to review...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19010218
更新日期：2018-01-11 00:00:00
abstract：:MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21062229
更新日期：2020-03-23 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are multipotent; non-hematopoietic stem cells. Because of their immunoregulatory abilities; MSCs are widely used for different clinical applications. Compared with that of other immune cells; the investigation of how MSCs specifically regulate B-cells has been superficial and insufficient...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms17050650
更新日期：2016-05-05 00:00:00
abstract：:Previous study revealed that a specific lignin-carbohydrate preparation, named as lignin-rich enzyme lignin (LREL) derived from plant husk, is a novel toll-like receptor 4 ligand and shows a potent immune-stimulatory activity against dendritic cells (DCs) in vitro. In this report, we investigated immune-stimulatory ac...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19010064
更新日期：2017-12-26 00:00:00
abstract：:Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular disease...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21155405
更新日期：2020-07-29 00:00:00
abstract：:The plant disease Phytophthora blight, caused by the oomycete pathogen Phytophthora capsici, is responsible for major economic losses in pepper production. Microtubules have been an attractive target for many antifungal agents as they are involved in key cellular events such as cell proliferation, signaling, and migra...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20112641
更新日期：2019-05-29 00:00:00
abstract：:Neuroblastoma (NB) is an aggressive, relapse-prone infancy tumor of the sympathetic nervous system and is the leading cause of death among preschool age diseases, so the search for novel therapeutic targets is crucial. Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development, and in the DNA ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20194764
更新日期：2019-09-25 00:00:00
abstract：:Natural killer (NK) cells are innate lymphoid cells that play a pivotal role in tumor surveillance. Exosomes are nanovesicles released into the extracellular environment via the endosomal vesicle pathway and represent an important mode of intercellular communication. The ability of anticancer chemotherapy to enhance t...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20030611
更新日期：2019-01-31 00:00:00
abstract：:The coupling of alternative splicing with the nonsense-mediated decay (NMD) pathway maintains quality control of the transcriptome in eukaryotes by eliminating transcripts with premature termination codons (PTC) and fine-tunes gene expression. Long noncoding RNA (lncRNA) can regulate multiple cellular processes, inclu...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21165605
更新日期：2020-08-05 00:00:00
abstract：:C-type lectin receptors and their adaptor molecules are involved in the recognition of glycosylated self-antigens and pathogens. However, little is known about the species- and organ-specific expression profiles of these molecules. We therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN, Syk,...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms130810113
更新日期：2012-01-01 00:00:00
abstract：:This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiograph...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms161125982
更新日期：2015-11-06 00:00:00
abstract：:Phosphoinositides play a crucial role in regulating many cellular functions, such as actin dynamics, signaling, intracellular trafficking, membrane dynamics, and cell-matrix adhesion. Central to this process is phosphatidylinositol bisphosphate (PIP2). The levels of PIP2 in the membrane are rapidly altered by the acti...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21218342
更新日期：2020-11-06 00:00:00
