scholarly journals CD98hc (SLC3A2) regulation of skin homeostasis wanes with age

2013 ◽  
Vol 210 (1) ◽  
pp. 173-190 ◽  
Author(s):  
Etienne Boulter ◽  
Soline Estrach ◽  
Aurélia Errante ◽  
Catherine Pons ◽  
Laurence Cailleteau ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Skin Aging ◽  
Amino Acid Transporters ◽  
Appreciable Effect ◽  
Nucleotide Exchange ◽  
Aged Skin

Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report that CD98hc invalidation has no appreciable effect on cell adhesion, clearly showing that CD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.

Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via Hypoxia-Inducible Factor-1α

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
Tetsuhiro Horie ◽  
Kazuya Fukasawa ◽  
Takashi Iezaki ◽  
Gyujin Park ◽  
Yuki Onishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypoxia Inducible Factor ◽  
Amino Acid Transporters ◽  
Hypoxic Stress ◽  
Gene Encoding ◽  
Brown Adipocytes ◽  
Hypoxia Inducible Factor 1Α ◽  
Brown Adipose

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxia-inducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia-responsive gene in brown adipocytes.

scholarly journals UVA Exposure Combined with Glycation of the Dermis Are Two Catalysts for Skin Aging and Promotes a Favorable Environment to the Appearance of Elastosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Hervé Pageon ◽  
Hélène Zucchi ◽  
Sylvie Ricois ◽  
Philippe Bastien ◽  
Daniel Asselineau
Keyword(s):  
Protein Expression ◽  
Biological Effect ◽  
Skin Aging ◽  
Chronological Aging ◽  
Advanced Glycosylation End Products ◽  
Uva Irradiation ◽  
Inflammatory State ◽  
Aged Skin

Skin aging is the result of superimposed intrinsic (individual) and extrinsic (e.g., UV exposure or nutrition) aging. Previous works have reported a relationship between UV irradiation and glycation in the aging process, leading, for example, to modified radical species production and the appearance of AGEs (advanced glycosylation end products) in increasing quantities, particularly glycoxidation products like pentosidine. In addition, the colocalization of AGEs and elastosis has also been observed. We first investigated the combination of the glycation reaction and UVA effects on a reconstructed skin model to explain their cumulative biological effect. We found that UVA exposure combined with glycation had the ability to intensify the response for specific markers: for example, MMP1 or MMP3 mRNA, proteases involved in extracellular matrix degradation, or proinflammatory cytokine, IL1α, protein expression. Moreover, the association of glycation and UVA irradiation is believed to promote an environment that favors the onset of an elastotic-like phenomenon: mRNA coding for elastin, elastase, and tropoelastin expression is increased. Secondly, because the damaging effects of UV radiation in vivo might be more detrimental in aged skin than in young skin due to increased accumulation of pentosidine and the exacerbation of alterations related to chronological aging, we studied the biological effect of soluble pentosidine in fibroblasts grown in monolayers. We found that pentosidine induced upregulation of CXCL2, IL8, and MMP12 mRNA expression (inflammatory and elastotic markers, respectively). Tropoelastin protein expression (elastin precursor) was also increased. In conclusion, fibroblasts in monolayers cultured with soluble pentosidine and tridimensional in vitro skin constructs exposed to the combination of AGEs and UVA promote an inflammatory state and an alteration of the dermal compartment in relation to an elastosis-like environment.

scholarly journals NEDD4 Regulates Ubiquitination and Stability of the Cell adhesion Molecule IGPR-1 via Lysosomal Pathway

2021 ◽  
Author(s):  
Linzi Sun ◽  
Razie Amraei ◽  
Nader Rahimi
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Molecular Mechanisms ◽  
E3 Ligase ◽  
Cell Surface Expression ◽  
Significant Implication ◽  
Ubiquitin E3 Ligase

ABSTRACTThe cell adhesion molecule immunoglobulin and proline-rich receptor-1 (IGPR-1) regulates various critical cellular processes including, cell-cell adhesion, mechanosensing and autophagy. However, the molecular mechanisms governing IGPR-1 cell surface expression levels remains unknown. In the present study, we used an in vitro ubiquitination assay and identified ubiquitin E3 ligase NEDD4 and the ubiquitin conjugating enzyme UbcH6 involved in the ubiquitination of IGPR-1. In vitro GST-pulldown and in vivo co-immunoprecipitation assays demonstrated that NEDD4 binds to IGPR-1. Over-expression of wild-type NEDD4 downregulated IGPR-1 and deletion of WW domains (1-4) of NEDD4 revoked its effects on IGPR-1. Similarly, knockdown of NEDD4 increased IGPR-1 levels in A375 melanoma cells. Furthermore, deletion of 57 amino acids encompassing polyproline rich (PPR) motif on the C-terminus of IGPR-1 nullified the binding of NEDD4 with IGPR-1. Moreover, we demonstrate that NEDD4 promotes K48- and K63-dependent polyubiquitination of IGPR-1. The NEDD4-mediated polyubiquitination of IGPR-1 stimulated lysosomal degradation of IGPR-1 as the treatment of cells with the lysosomal inhibitors, bafilomycine and ammonium chloride increased IGPR-1 levels in the HEK-293 cells ectopically expressing IGPR-1 and in multiple human skin melanoma cell lines. Hence, these findings suggest that ubiquitin E3 ligase NEDD4 is a key regulator of IGPR-1 with a significant implication in the therapeutic targeting of IGPR-1.

scholarly journals Antimicrobial Peptide TP4 Targets Mitochondrial Adenine Nucleotide Translocator 2

Marine Drugs ◽  
2020 ◽  
Vol 18 (8) ◽  
pp. 417
Author(s):  
Bor-Chyuan Su ◽  
Yi-Chung Liu ◽  
Chen-Hung Ting ◽  
Ping-Chiang Lyu ◽  
Jyh-Yih Chen
Keyword(s):  
Antimicrobial Peptide ◽  
Molecular Mechanisms ◽  
Adenine Nucleotide ◽  
Docking Studies ◽  
Adenine Nucleotide Translocator ◽  
Nucleotide Exchange ◽  
Nile Tilapia Oreochromis Niloticus ◽  
Key Residues

Tilapia piscidin (TP) 4 is an antimicrobial peptide derived from Nile tilapia (Oreochromis niloticus), which shows broad-spectrum antibacterial activity and excellent cancer-killing ability in vitro and in vivo. Like many other antimicrobial peptides, TP4 treatment causes mitochondrial toxicity in cancer cells. However, the molecular mechanisms underlying TP4 targeting of mitochondria remain unclear. In this study, we used a pull-down assay on A549 cell lysates combined with LC-MS/MS to discover that TP4 targets adenine nucleotide translocator (ANT) 2, a protein essential for adenine nucleotide exchange across the inner membrane. We further showed that TP4 accumulates in mitochondria and colocalizes with ANT2. Moreover, molecular docking studies showed that the interaction requires Phe1, Ile2, His3, His4, Ser11, Lys14, His17, Arg21, Arg24 and Arg25 residues in TP4 and key residues within the cavity of ANT2. These findings suggest a mechanism by which TP4 may induce mitochondrial dysfunction to disrupt cellular energy metabolism.

scholarly journals Posttranslational modification of the RHO of plants protein RACB by phosphorylation and cross-kingdom conserved ubiquitination

2020 ◽  
Author(s):  
Lukas Weiß ◽  
Tina Reiner ◽  
Julia Mergner ◽  
Bernhard Kuster ◽  
Attila Fehér ◽  
...  
Keyword(s):  
Amino Acid ◽  
Posttranslational Modification ◽  
Individual Case ◽  
Bound State ◽  
Amino Acid Residues ◽  
Nucleotide Exchange ◽  
Protein Activity ◽  
Developmental Defects

AbstractSmall RHO-type G-proteins act as signaling hubs and master regulators of polarity in eukaryotic cells. Their activity is tightly controlled, as defective RHO signaling leads to aberrant growth and developmental defects. Two major pathways regulate G-protein activity: canonical switching of the nucleotide bound state and posttranslational modification (PTM). PTMs can support or suppress RHO signaling, depending on each individual case. In plants, regulation of Rho of plants (ROPs) has been shown to act through nucleotide exchange and hydrolysis, as well as through lipid modification, but there is little data available on phosphorylation or ubiquitination of ROPs. Hence, we applied proteomic analyses to identify PTMs of the barley ROP RACB. We observed in vitro phosphorylation by barley ROP Binding Kinase 1 and in vivo ubiquitination of RACB. Comparative analyses of the newly identified RACB phosphosites and human RHO protein phosphosites revealed conservation of modified amino acid residues, but no overlap of actual phosphorylation patterns. However, the identified RACB ubiquitination site is present in all ROPs from Hordeum vulgare, Arabidopsis thaliana and Oryza sativa. Since this highly conserved amino acid residue is likewise ubiquitinated in mammalian Rac1 and Rac3, we suggest that RHO family proteins from different kingdoms could be generally regulated by ubiquitination of this site.

scholarly journals RTH-149 Cell Line, a Useful Tool to Decipher Molecular Mechanisms Related to Fish Nutrition

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1754
Author(s):  
Guillaume Morin ◽  
Karine Pinel ◽  
Karine Dias ◽  
Iban Seiliez ◽  
Florian Beaumatin
Keyword(s):  
Amino Acid ◽  
Cell Line ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Fish Nutrition ◽  
Multiple Strategies ◽  
First Time ◽  
Interesting Alternative

Nowadays, aquaculture provides more than 50% of fish consumed worldwide but faces new issues that challenge its sustainability. One of them relies on the replacement of fish meal (FM) in aquaculture feeds by other protein sources without deeply affecting the whole organism’s homeostasis. Multiple strategies have already been tested using in vivo approaches, but they hardly managed to cope with the multifactorial problems related to the complexities of fish biology together with new feed formulations. In this context, rainbow trout (RT) is particularly concerned by these problems, since, as a carnivorous fish, dietary proteins provide the amino acids required to supply most of its energetic metabolism. Surprisingly, we noticed that in vitro approaches considering RT cell lines as models to study RT amino acid metabolism were never previously used. Therefore, we decided to investigate if, and how, three major pathways described, in other species, to be regulated by amino acid and to control cellular homeostasis were functional in a RT cell line called RTH-149—namely, the mechanistic Target Of Rapamycin (mTOR), autophagy and the general control nonderepressible 2 (GCN2) pathways. Our results not only demonstrated that these three pathways were functional in RTH-149 cells, but they also highlighted some RT specificities with respect to the time response, amino acid dependencies and the activation levels of their downstream targets. Altogether, this article demonstrated, for the first time, that RT cell lines could represent an interesting alternative of in vivo experimentations for the study of fish nutrition-related questions.

scholarly journals Impaired Placental Nutrient Transport in Mice Generated by in Vitro Fertilization

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3457-3467 ◽  
Author(s):  
Enrrico Bloise ◽  
Wingka Lin ◽  
Xiaowei Liu ◽  
Rhodel Simbulan ◽  
Kevin S. Kolahi ◽  
...  
Keyword(s):  
Birth Weight ◽  
Amino Acid ◽  
In Vitro Fertilization ◽  
Control Group ◽  
Amino Acid Transporters ◽  
Vitro Fertilization ◽  
Placental Function ◽  
Placental Transport

More than 4.5 million children have been conceived by in vitro fertilization (IVF). Interestingly, singleton IVF offspring born at term have an increased incidence of low birth weight. The mechanism responsible for the lower birth weight is unknown, but alterations in placental function are possible. Hence, the goal of our study was to examine placental growth and function in mice generated in vivo or in vitro. To assess placental function, blastocysts were generated by IVF or produced by natural mating (control group); both IVF and control blastocysts were transferred to pseudopregnant recipients. Placental weights did not differ at embryonic d 15.5 (E15.5) but were increased at E18.5 in the IVF group (25.4%, P < 0.001) compared with control. Proliferation was increased in IVF placentae, whereas overall placental gross morphology and apoptosis were not affected. Both fetal weights (16.4% lower at E15.5 and 8.8% lower at E18.5, P < 0.05) and fetal to placental ratios were lower (P < 0.001) in the IVF compared with the control group at both time points, whereas birth weights did not differ. At E18.5, the mRNA for selected glucose, system A amino acid transporters, and imprinted genes were down-regulated in IVF placentae. GLUT3 protein level was decreased in the IVF group (P < 0.05). Importantly, intrajugular injections of 14C-methyl-d-glucose or 14C-MeAIB tracers (n = 6 litters per group) showed that placental transport of glucose and amino acids were 24.8% (not significant) and 58.1% (P < 0.05) lower in the IVF group. Fetal accumulation of glucose was not different, but amino acid accumulation was significantly (36 %) lower in IVF fetuses (P < 0.05). We conclude that IVF alters both fetal and placental growth and, importantly, decreases placental transport efficiency in mice conceived by IVF.

scholarly journals Regulation of polyribosome formation and protein synthesis in the uterus. Effect of administration of graded doses of oestradiol-17β and actinomycin D on the amino acid-incorporation activity in vitro and the cytoplasmic concentration in vivo of polyribosomes

1970 ◽  
Vol 118 (3) ◽  
pp. 341-346 ◽  
Author(s):  
Ching-Sung Teng ◽  
Terrell H. Hamilton
Keyword(s):  
Amino Acid ◽  
Molecular Mechanisms ◽  
Actinomycin D ◽  
Amino Acid Incorporation ◽  
Free System ◽  
Acid Incorporation ◽  
Minimal Dose ◽  
Early Action

1. The effects of graded doses of oestradiol-17β and actinomycin D, administered separately or together, on the amino acid-incorporation activity in vitro and the cytoplasmic concentration in vivo of uterine polyribosomes are described. Preparations of polyribosomes isolated from uteri of ovariectomized adult rats were determined for cytoplasmic concentration in vivo and assayed for [14C]leucine-incorporation activity in the cell-free system, exactly as described by Teng & Hamilton (1967b). 2. A minimal dose of 10μg of oestradiol-17β administered for 10h was found to increase, by about 100%, both the amino acid-incorporation activity in vitro and the cytoplasmic concentration in vivo of the polyribosomes. A minimal dose of 250μg of actinomycin D administered for 10h was found to inhibit, by about 50%, the incorporation activity in vitro of the polyribosomes. All doses of the inhibitor administered for 10h failed to alter the cytoplasmic concentration in vivo of the polyribosomes. 3. A dose of 10μg of oestradiol-17β restored to the control value the inhibitory effect of a dose of either 50 or 125μg of actinomycin D on the activity in vitro of the polyribosomes, at 10h after treatment with the inhibitor and the hormone. In these experiments, there was an increase of 60–100% in the cytoplasmic concentration in vivo of the polyribosomes. 4. A dose of 125μg of actinomycin D, administered to animals along with 10μg of oestradiol-17β for 6–36h, abolished the hormone-induced enhancement of the incorporation activity in vitro, but did not prevent an increase of about 200% in the cytoplasmic concentration in vivo of the polyribosomes. However, treatment with 750μg of the inhibitor abolished both stimulatory effects of the hormone. 5. The results reported indicate that the stimulatory effects of oestradiol-17β in vivo on the number and activity of the cytoplasmic polyribosomes in the uterus of the ovariectomized rat have different sensitivities to actinomycin D, but the primary molecular mechanisms responsible for the results are unknown. The major conclusion drawn is that the formation and appearance in the cytoplasm of newly formed polyribosomes are important features of the early action of oestrogen in the uterus.

scholarly journals Galactose-Induced Skin Aging: The Role of Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Bauyrzhan Umbayev ◽  
Sholpan Askarova ◽  
Aigul Almabayeva ◽  
Timur Saliev ◽  
Abdul-Razak Masoud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Skin Diseases ◽  
Skin Aging ◽  
Covalent Attachment ◽  
Advanced Glycation ◽  
Glycation End Products

Skin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable of damaging the skin’s vital components through nonenzymatic glycation, the covalent attachment of sugar to a protein, and subsequent production of advanced glycation end products (AGEs). This review is focused on the role of D-galactose in the development of skin aging and its relation to oxidative stress. The interest in this problem was dictated by recent findings that used in vitro and in vivo models. The review highlights the recent advances in the underlying molecular mechanisms of D-galactose-mediated cell senescence and cytotoxicity. We have also proposed the possible impact of galactosemia on skin aging and its clinical relevance. The understanding of molecular mechanisms of skin aging mediated by D-galactose can help dermatologists optimize methods for prevention and treatment of skin senescence and aging-related skin diseases.

Sign in / Sign up

Export Citation Format

Share Document