Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia

Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.

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Glucose regulates tissue-specific chondro-osteogenic differentiation of human cartilage endplate stem cells via O-GlcNAcylation of Sox9 and Runx2

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1440-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Chao Sun ◽

Weiren Lan ◽

Bin Li ◽

Rui Zuo ◽

Hui Xing ◽

...

Keyword(s):

Western Blot ◽

Osteogenic Differentiation ◽

High Glucose ◽

Immunohistochemical Staining ◽

Chondrogenic Differentiation ◽

Glucose Medium ◽

Cartilage Endplate ◽

High Glucose Medium ◽

Differentiation Medium ◽

Low Glucose

Abstract Background The degenerative disc disease (DDD) is a major cause of low back pain. The physiological low-glucose microenvironment of the cartilage endplate (CEP) is disrupted in DDD. Glucose influences protein O-GlcNAcylation via the hexosamine biosynthetic pathway (HBP), which is the key to stem cell fate. Thiamet-G is an inhibitor of O-GlcNAcase for accumulating O-GlcNAcylated proteins while 6-diazo-5-oxo-l-norleucine (DON) inhibits HBP. Mechanisms of DDD are incompletely understood but include CEP degeneration and calcification. We aimed to identify the molecular mechanisms of glucose in CEP calcification in DDD. Methods We assessed normal and degenerated CEP tissues from patients, and the effects of chondrogenesis and osteogenesis of the CEP were determined by western blot and immunohistochemical staining. Cartilage endplate stem cells (CESCs) were induced with low-, normal-, and high-glucose medium for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. CESCs were induced with low-glucose and high-glucose medium with or without Thiamet-G or DON for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. Sox9 and Runx2 O-GlcNAcylation were measured by immunofluorescence. The effects of O-GlcNAcylation on the downstream genes of Sox9 and Runx2 were determined by Q-PCR and western blot. Results Degenerated CEPs from DDD patients lost chondrogenesis, acquired osteogenesis, and had higher protein O-GlcNAcylation level compared to normal CEPs from LVF patients. CESC chondrogenic differentiation gradually decreased while osteogenic differentiation gradually increased from low- to high-glucose differentiation medium. Furthermore, Thiamet-G promoted CESC osteogenic differentiation and inhibited chondrogenic differentiation in low-glucose differentiation medium; however, DON acted opposite role in high-glucose differentiation medium. Interestingly, we found that Sox9 and Runx2 were O-GlcNAcylated in differentiated CESCs. Finally, O-GlcNAcylation of Sox9 and Runx2 decreased chondrogenesis and increased osteogenesis in CESCs. Conclusions Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic and osteogenic differentiation potential of CESCs and provide insight into the mechanism of how glucose concentration regulates Sox9 and Runx2 O-GlcNAcylation to affect the differentiation of CESCs, which may represent a target for CEP degeneration therapy.

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Dipeptide transport in brush-border membrane vesicles isolated from normal term human placenta

American Journal of Obstetrics and Gynecology ◽

10.1016/0002-9378(85)90600-3 ◽

1985 ◽

Vol 153 (1) ◽

pp. 83-86 ◽

Cited By ~ 32

Author(s):

Malliga E. Ganapathy ◽

Virendra B. Mahesh ◽

Lawrence D. Devoe ◽

Frederick H. Leibach ◽

Vadivel Ganapathy

Keyword(s):

Human Placenta ◽

Brush Border ◽

Brush Border Membrane ◽

Membrane Vesicles ◽

Brush Border Membrane Vesicles ◽

Normal Term ◽

Dipeptide Transport

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Effect of glucose concentration in the growth medium on the synthesis of fatty acids by the yeast Candida bogoriensis

Canadian Journal of Microbiology ◽

10.1139/m82-030 ◽

1982 ◽

Vol 28 (2) ◽

pp. 223-230 ◽

Cited By ~ 5

Author(s):

Adrian J. Cutler ◽

Robley J. Light

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acid ◽

Yeast Extract ◽

Fatty Acid Synthesis ◽

Acid Synthesis ◽

Glucose Medium ◽

Triglyceride Fraction ◽

Low Glucose ◽

Stimulation Of

The yeast Candida bogoriensis produced large quantities of an extracellular glycolipid, the diacetyl sophoroside of 13-hydroxydocosanoic acid, when grown on a standard glucose rich medium (3% glucose, 0.15% yeast extract), but not when grown on a low glucose medium (0.5% glucose, 0.4% yeast extract) (A. J. Cutler and R. J. Light. 1979. J. Biol. Chem. 254: 1944–1950). Glucose levels also affected the quantity and distribution of the free fatty acid and triglyceride fractions synthesized by this organism. Cells grown on the low glucose medium contained palmitate and stearate as the major fatty acids in these two fractions, and a 3-h incubation with [1-14C]acetate led primarily to the labeling of these two acids. Cells grown on the standard enriched glucose medium contained relatively less stearate and more behenate than the low glucose grown cells, and the incorporation of [1-14C]acetate into stearate was decreased, while that into behenate was increased.Supplementation of low glucose grown cells with glucose led to a rapid stimulation of fatty acid synthesis, primarily palmitate and stearate in the free fatty acid fraction and stearate in the triglyceride fraction. Total triglyceride began to increase a few hours after supplementation, but synthesis of the extracellular glycolipid, and hence 13-hydroxydocosanoic acid, did not occur until 12–24 h after supplementation. The stimulation by glucose of long chain fatty acid synthesis in C. bogoriensis was therefore a process distinct from the glucose stimulation of palmitate and stearate synthesis, though the two events may be causally related.

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Lactic Acid Bacteria in Wine: Technological Advances and Evaluation of Their Functional Role

Frontiers in Microbiology ◽

10.3389/fmicb.2020.612118 ◽

2021 ◽

Vol 11 ◽

Author(s):

Carla Virdis ◽

Krista Sumby ◽

Eveline Bartowsky ◽

Vladimir Jiranek

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Future Research ◽

Main Role ◽

Wine Aroma ◽

Technological Advances ◽

Pectinolytic Activity ◽

Volatile Thiols ◽

Microbial Stability ◽

Enzymatic Pathways

Currently, the main role of Lactic Acid Bacteria (LAB) in wine is to conduct the malolactic fermentation (MLF). This process can increase wine aroma and mouthfeel, improve microbial stability and reduce the acidity of wine. A growing number of studies support the appreciation that LAB can also significantly, positively and negatively, contribute to the sensorial profile of wine through many different enzymatic pathways. This is achieved either through the synthesis of compounds such as diacetyl and esters or by liberating bound aroma compounds such as glycoside-bound primary aromas and volatile thiols which are odorless in their bound form. LAB can also liberate hydroxycinnamic acids from their tartaric esters and have the potential to break down anthocyanin glucosides, thus impacting wine color. LAB can also produce enzymes with the potential to help in the winemaking process and contribute to stabilizing the final product. For example, LAB exhibit peptidolytic and proteolytic activity that could break down the proteins causing wine haze, potentially reducing the need for bentonite addition. Other potential contributions include pectinolytic activity, which could aid juice clarification and the ability to break down acetaldehyde, even when bound to SO2, reducing the need for SO2 additions during winemaking. Considering all these findings, this review summarizes the novel enzymatic activities of LAB that positively or negatively affect the quality of wine. Inoculation strategies, LAB improvement strategies, their potential to be used as targeted additions, and technological advances involving their use in wine are highlighted along with suggestions for future research.

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SNAT4 isoform of system A amino acid transporter is expressed in human placenta

AJP Cell Physiology ◽

10.1152/ajpcell.00258.2005 ◽

2006 ◽

Vol 290 (1) ◽

pp. C305-C312 ◽

Cited By ~ 78

Author(s):

M. Desforges ◽

H. A. Lacey ◽

J. D. Glazier ◽

S. L. Greenwood ◽

K. J. Mynett ◽

...

Keyword(s):

Amino Acid ◽

Protein Expression ◽

Western Blot ◽

Human Placenta ◽

Blot Analysis ◽

First Trimester ◽

Amino Acid Transporter ◽

Full Term ◽

System A ◽

Acid Transporter

The system A amino acid transporter is encoded by three members of the Slc38 gene family, giving rise to three subtypes: Na+-coupled neutral amino acid transporter (SNAT)1, SNAT2, and SNAT4. SNAT2 is expressed ubiquitously in mammalian tissues; SNAT1 is predominantly expressed in heart, brain, and placenta; and SNAT4 is reported to be expressed solely by the liver. In the placenta, system A has an essential role in the supply of neutral amino acids needed for fetal growth. In the present study, we examined expression and localization of SNAT1, SNAT2, and SNAT4 in human placenta during gestation. Real-time quantitative PCR was used to examine steady-state levels of system A subtype mRNA in early (6–10 wk) and late (10–13 wk) first-trimester and full-term (38–40 wk) placentas. We detected mRNA for all three isoforms from early gestation onward. There were no differences in SNAT1 and SNAT2 mRNA expression with gestation. However, SNAT4 mRNA expression was significantly higher early in the first trimester compared with the full-term placenta ( P < 0.01). We next investigated SNAT4 protein expression in human placenta. In contrast to the observation for gene expression, Western blot analysis revealed that SNAT4 protein expression was significantly higher at term compared with the first trimester ( P < 0.05). Immunohistochemistry and Western blot analysis showed that SNAT4 is localized to the microvillous and basal plasma membranes of the syncytiotrophoblast, suggesting a role for this isoform of system A in amino acid transport across the placenta. This study therefore provides the first evidence of SNAT4 mRNA and protein expression in the human placenta, both at the first trimester and at full term.

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The Role of Yeasts and Lactic Acid Bacteria on the Metabolism of Organic Acids during Winemaking

Foods ◽

10.3390/foods9091231 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1231 ◽

Cited By ~ 1

Author(s):

Ana Mendes Ferreira ◽

Arlete Mendes-Faia

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Alcoholic Fermentation ◽

Main Role ◽

Wine Yeasts ◽

Grape Berries ◽

Multiple Reactions ◽

Wine Composition ◽

Microbial Stability

The main role of acidity and pH is to confer microbial stability to wines. No less relevant, they also preserve the color and sensory properties of wines. Tartaric and malic acids are generally the most prominent acids in wines, while others such as succinic, citric, lactic, and pyruvic can exist in minor concentrations. Multiple reactions occur during winemaking and processing, resulting in changes in the concentration of these acids in wines. Two major groups of microorganisms are involved in such modifications: the wine yeasts, particularly strains of Saccharomyces cerevisiae, which carry out alcoholic fermentation; and lactic acid bacteria, which commonly conduct malolactic fermentation. This review examines various such modifications that occur in the pre-existing acids of grape berries and in others that result from this microbial activity as a means to elucidate the link between microbial diversity and wine composition.

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Effect of carbohydrates on lipid metabolism during porcine oocyte IVM

Reproduction Fertility and Development ◽

10.1071/rd18043 ◽

2019 ◽

Vol 31 (3) ◽

pp. 557 ◽

Cited By ~ 4

Author(s):

Jenna L. Lowe ◽

Roslyn Bathgate ◽

Christopher G. Grupen

Keyword(s):

Lipid Metabolism ◽

Lipid Droplets ◽

Inhibitory Effect ◽

Carnitine Supplementation ◽

Glucose Medium ◽

Nuclear Maturation ◽

Endogenous Lipid ◽

Porcine Oocyte ◽

Low Glucose ◽

Cytoplasmic Maturation

Porcine oocytes contain a large amount of endogenous lipid, which is thought to function as an intracellular source of energy. The aim of this study was to determine the effects of stimulating or inhibiting lipid metabolism using l-carnitine or etomoxir respectively on the IVM of porcine oocytes cultured in media of varying carbohydrate composition. In the presence of pyruvate and lactate, exclusion of glucose inhibited oocyte nuclear and cytoplasmic maturation compared with oocytes matured in media containing low (1.5mM) and high (4.0mM) concentrations of glucose. In the absence of pyruvate and lactate in low-glucose medium only, a greater proportion of l-carnitine-treated oocytes progressed to the MII stage compared with untreated oocytes. The inclusion of pyruvate and lactate significantly altered the distribution of cytoplasmic lipid droplets and elevated the ATP content of oocytes, whereas the l-carnitine treatment did not. Further, the inhibitory effect of etomoxir on nuclear maturation was decreased in high- compared with low-glucose medium. The results indicate that carbohydrate substrates are absolutely necessary for effective porcine oocyte maturation, and that l-carnitine supplementation can only partially compensate for deficiencies in carbohydrate provision.

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Kinetics analysis of growth and lactic acid production in pH-controlled batch cultures of Lactobacillus casei KH-1 using yeast extract/corn steep liquor/glucose medium

Journal of Bioscience and Bioengineering ◽

10.1016/s1389-1723(03)90115-0 ◽

2003 ◽

Vol 96 (2) ◽

pp. 134-140 ◽

Cited By ~ 29

Author(s):

Mi-Young Ha ◽

Si-Wouk Kim ◽

Yong-Woon Lee ◽

Myong-Jun Kim ◽

Seong-Jun Kim

Keyword(s):

Lactic Acid ◽

Yeast Extract ◽

Acid Production ◽

Lactobacillus Casei ◽

Corn Steep Liquor ◽

Lactic Acid Production ◽

Glucose Medium ◽

Kinetics Analysis ◽

Batch Cultures ◽

Steep Liquor

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Flow Cytometry for Evaluation of EGFR-mTOR Signal Way in the Growth Inhibitory Rate of Hela Cell Under Low Glucose and High Lactic Acid Environment

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2019.2637 ◽

2019 ◽

Vol 9 (2) ◽

pp. 324-328

Author(s):

Li Ping ◽

Li Mingzhu ◽

Lü Yuchun

Keyword(s):

Flow Cytometry ◽

Lactic Acid ◽

Hela Cell ◽

Expression Level ◽

Inhibitory Rate ◽

Growth Inhibitory ◽

Significant Difference ◽

Normal Glucose ◽

Acid Environment ◽

Low Glucose

Objective: To discuss the effect of EGFR-mTOR signal way in the adaption of cervical carcinoma cell in low glucose and high lactic acid. Methods: Hela cells were cultured in four conditions: normal glucose (NG, glucose 10 mmol/L), low glucose (LG, glucose 3 mmol/L), high lactic acid (HL, lactic acid 2.5 mmol/L) and low glucose and high lactic acid (LGHL, glucose 10 mmol/L, lactic acid 2.5 mmol/L). Growth inhibitory rate of Hela cell was determined by CCK-8; Flow cytometry (FCM) was performed to evaluate the cell cycle; Results: Compared with the rate in NG, the rate in low glucose and high lactic acid was significantly increased (P < 0.01). Compared with the rate in NG, the rate of G1/G0 was increased in HL and in LGHL (P < 0.01, P < 0.01); the rate of G1/G0 in LG didn't have significant difference; the rates of G2/M in HL and in LGHL were decreased, and the G2/M rate in LG was increased, but all of them had no statistically significant. The rates of S were decreased in HL, LG and LGHL (P < 0.05, no statistically significant, P < 0.05). The expression level of EGFR mRNA in Hela was decreased and the level of mTOR mRNA was increased in HL (both had no statistically significant), when compared with the levels in NG. The expression level of EGFR mRNA was decreased (P < 0.05) and the level of mTOR mRNA was a little increased (no statistically significant) in LG; while the EGFR and mTOR expression levels were increased in LGHL (P < 0.05). Conclusion: Low glucose and high lactic acid environment is conducive to Hela cell survival, and can promote the expression of EGFR and mTOR.

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