Blastocyst metabolism

2015 ◽  
Vol 27 (4) ◽  
pp. 638 ◽  
Author(s):  
David K. Gardner ◽  
Alexandra J. Harvey
Keyword(s):  
Immune Modulation ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Metabolic Stress ◽  
Glucose Consumption ◽  
Blastocyst Stage ◽  
X Chromosomes ◽  
Amino Acid Turnover ◽  
Amp Activated Protein Kinase ◽  
Local Immune Modulation

The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its unique physiology and its ability to undergo implantation. Glucose is the primary nutrient of the blastocyst, and is metabolised both oxidatively and through aerobic glycolysis. The production of significant quantities of lactate by the blastocyst reflects specific metabolic requirements and mitochondrial regulation; it is further proposed that lactate production serves to facilitate several key functions during implantation, including biosynthesis, endometrial tissue breakdown, the promotion of new blood vessel formation and induction of local immune-modulation of the uterine environment. Nutrient availability, oxygen concentration and the redox state of the blastocyst tightly regulate the relative activities of specific metabolic pathways. Notably, a loss of metabolic normality is associated with a reduction in implantation potential and subsequent fetal development. Even a transient metabolic stress at the blastocyst stage culminates in low fetal weights after transfer. Further, it is evident that there are differences between male and female embryos, with female embryos being characterised by higher glucose consumption and differences in their amino acid turnover, reflecting the presence of two active X-chromosomes before implantation, which results in differences in the proteomes between the sexes. In addition to the role of Hypoxia-Inducible Factors, the signalling pathways involved in regulating blastocyst metabolism are currently under intense analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and specific amino acids being scrutinised. It is evident that blastocyst metabolism regulates more than the production of ATP; rather, it is apparent that metabolites and cofactors are important regulators of the epigenome, putting metabolism at centre stage when considering the interactions of the blastocyst with its environment.

scholarly journals ROCK2 promotes osteosarcoma growth and glycolysis by up-regulating HKII via phospho- PI3K/AKT signalling

2020 ◽  
Author(s):  
Xue qaing Deng ◽  
Jianyong Deng ◽  
Xuan Yi ◽  
Yeqing Zou ◽  
Liang Hao
Keyword(s):  
Colony Formation ◽  
Aerobic Glycolysis ◽  
Bone Tumour ◽  
Lactate Production ◽  
Metabolic Stress ◽  
Glucose Consumption ◽  
Metabolic Reprogramming ◽  
Hexokinase Ii ◽  
Protein Expressions ◽  
Key Enzyme

Abstract Background Osteosarcoma (OS) is a malignant bone tumour that exhibits a high mortality. While tumours thrive in a state of malnutrition, the mechanism by which OS cells adapt to metabolic stress through metabolic reprogramming remains unclear. Methods We analysed the expression of ROCK2 in osteosarcoma patients by RT-qPCR and Western blot. Cell proliferation, and colony formation were analysed using CCK8, EdU assays and colony formation assays. The level of Cell glycolysis was detected by glucose-6 phosphate, glucose consumption, lactate production and ATP levels. Results Herein, our study showed that ROCK2 expression in OS was higher than in adjacent tissues. Functional assays have demonstrated that ROCK2 contributes to the growth of OS cells by inducing aerobic glycolysis. The current study revealed that ROCK2 knockdown decreased the levels of mitochondrial hexokinase II (HKII). And also indicated that ROCK2 served as a key enzyme in glycolysis and that it served an important role in tumour growth and metastasis. A significant positive correlation was identified between the mRNA and protein expressions of ROCK2 and HKII, further demonstrating that ROCK2-induced glycolysis and proliferation was dependent on HKII in OS cells. Mechanistically, ROCK2 promotes HKII expression by activating the phospho-PI3K/AKT signalling pathway. Conclusions Taken together, the results of the current study linked the two drivers of OS growth and aerobic glycolysis, and identified a new mechanism of ROCK2 control in OS.

scholarly journals ROCK2 promotes osteosarcoma growth and glycolysis by up-regulating HKII via phospho-PI3K/AKT signalling

2020 ◽  
Author(s):  
Xue qaing Deng ◽  
Jianyong Deng ◽  
Xuan Yi ◽  
Yeqing Zou ◽  
Liang Hao
Keyword(s):  
Aerobic Glycolysis ◽  
Bone Tumour ◽  
Lactate Production ◽  
Metabolic Stress ◽  
Glucose Consumption ◽  
Metabolic Reprogramming ◽  
Hexokinase Ii ◽  
Functional Assays ◽  
Protein Expressions ◽  
Key Enzyme

Abstract Background: Osteosarcoma (OS) is a malignant bone tumour that exhibits a high mortality. While tumours thrive in a state of malnutrition, the mechanism by which OS cells adapt to metabolic stress through metabolic reprogramming remains unclear. Methods: We analysed the expression of ROCK2 in osteosarcoma tissues by RT-qPCR and Western blot. Cell proliferation were analysed using CCK8, EdU and colony formation assays. The level of Cell glycolysis was detected by glucose-6 phosphate, glucose consumption, lactate production and ATP levels.Results: Herein, our study showed that ROCK2 expression in OS tissues was higher than in adjacent tissues. Functional assays have demonstrated that ROCK2 contributes to the growth of OS cells by inducing aerobic glycolysis. The current study revealed that ROCK2 knockdown decreased the levels of mitochondrial hexokinase II (HKII). And also indicated that ROCK2 served as a key enzyme in glycolysis and that it served an important role in tumour growth. A significant positive correlation was identified between the mRNA and protein expressions of ROCK2 and HKII, further demonstrating that ROCK2-induced glycolysis and proliferation was dependent on HKII expression in OS cells. Mechanistically, ROCK2 promotes HKII expression by activating the phospho-PI3K/AKT signalling pathway. Conclusions: Taken together, the results of the current study linked the two drivers of OS growth and aerobic glycolysis, and identified a new mechanism of ROCK2 control in OS.

scholarly journals Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

2020 ◽  
Vol 21 (5) ◽  
pp. 1661
Author(s):  
Anamarija Mojzeš ◽  
Marko Tomljanović ◽  
Lidija Milković ◽  
Renata Novak Kujundžić ◽  
Ana Čipak Gašparović ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Intracellular Localization ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Warburg Effect

In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant.

scholarly journals FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Weixing Dai ◽  
Xianke Meng ◽  
Shaobo Mo ◽  
Wenqiang Xiang ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Underlying Mechanism ◽  
Low Expression

Abstract Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.

scholarly journals LINC00665 Targets miR-214-3p/MAPK1 Axis to Accelerate Hepatocellular Carcinoma Growth and Warburg Effect

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hongyu Wan ◽  
Yi Tian ◽  
Juan Zhao ◽  
Xiao Su
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Colony Formation ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Tumor Formation ◽  
Luciferase Reporter

Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation in vivo. Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.

Aerobic Glycolysis: A Possible Target for Treating Multiple Myeloma (MM) with High Serum LDH Levels

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1799-1799 ◽  
Author(s):  
Shiho Fujiwara ◽  
Yawara Kawano ◽  
Hiromichi Yuki ◽  
Yutaka Okuno ◽  
Kisato Nosaka ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
High Serum ◽  
Expression Levels ◽  
Key Enzyme ◽  
The Warburg Effect

Abstract Abstract 1799 Introduction: A number of studies have shown that the high level of serum lactate dehydrogenase (LDH) serves as an indicator for poor prognosis in multiple myeloma (MM). LDH is a key enzyme for glycolysis converting pyruvate to lactate, which is eventually utilized as an energy source particularly in tumor cells. It has been reported that cancer cells utilize this glycolysis pathway even in the presence of adequate oxygen to provide cancer cells with energy, called the Warburg effect (aerobic glycolysis). Myc is known to regulate LDH and pyruvate dehydrogenase kinase 1 (PDK1), which are master regulators of glycolysis (Figure 1). Although myc is a well known gene expressed in MM cells, there has been no report analyzing its association with the glycolysis-regulating genetic system, which is located downstream to the myc gene, in MM cells. In the present study, we examined if the glycolysis system is directly or indirectly associated with the survival of MM cells. Methods: MM cells were purified from primary bone marrow samples from 54 patients using CD138-magnetic beads. Written informed consent was obtained from all cases. Seven MM cell lines, RPMI8226, U266, KMS12BM, KMS12PE, KHM11, KMM1 and KMS11, were employed. Five genes associated with glycolysis, i.e., c-MYC, GLUT1 (glucose transporter 1), LDHA (LDH-encoding gene), hypoxia induced factor-1 alpha (HIF1a) and PDK1, were examined using real time PCR analysis. Glucose consumption and lactate production in culture supernatants of MM cell lines were analyzed. Oxamate, a competitive inhibitor of LDHA, was utilized to quantify cytotoxic effects on MM cells. Cytotoxicity was evaluated with AnnexinV/PI staining. Results: Heterogeneous expression of LDHA gene was observed (Figure 2A). High LDHA mRNA expression levels significantly correlated with poor survival (Figure 2B, p<0.01). A significant correlation between serum LDH levels and the mRNA expression levels of LDHA, was also found (p<0.01). Moreover, LDHA mRNA expression was significantly higher in MM cells than in plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS) (p<0.01). LDHA expression levels correlated with the expression levels of (i) c-MYC (p<0.0001) (ii) PDK1 (p<0.0023), a key enzyme regulating the Warburg effect, and (iii) GLUT1 (p<0.0003), while it did not correlate with HIF1a expression. It was also found that the greater glucose consumption, the greater lactate production as well as LDH activity in MM cell lines with higher LDHA mRNA expression. Finally, we found that an LDH-inhibitor, oxamate, activated caspase-3 (Figure 3) and induced apoptosis in MM cell lines as well as primary MM cells. Conclusion: Our results suggest that aerobic glycolysis (the Warburg effect) is up-regulated in MM cells of patients with high serum LDH levels and that the aberrant expression of LDHA, PDK1 and GLUT1 is critical for the survival of MM cells with high serum LDH levels. Thus, aerobic glycolysis itself could serve as a novel therapeutic target in MM patients. Since MM with high serum LDH is with poor prognosis even after the advent of new agents, the present data might have a clinical relevance and might open a new avenue to develop novel therapeutic modalities for treating MM with high serum LDH levels. Disclosures: No relevant conflicts of interest to declare.

miR-206 regulates non-small-cell lung cancer cell aerobic glycolysis by targeting hexokinase 2

2019 ◽  
Vol 167 (4) ◽  
pp. 365-370 ◽  
Author(s):  
Ke-Gang Jia ◽  
Gang Feng ◽  
Yu-Suo Tong ◽  
Guang-Zhou Tao ◽  
Lian Xu
Keyword(s):  
Colony Formation ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Hexokinase 2 ◽  
Lung Cancers ◽  
Atp Generation

Abstract Aerobic glycolysis was closely associated with the malignant transformation and prognosis of tumours. miR-206 was found to be downregulated in several cancers. However, whether miR-206 functions in non-small-cell lung cancers (NSCLCs) via the process of aerobic glycolysis remains poorly characterized. Quantitative real-time PCR was performed to detect miR-206 level in NSCLC cells and tissues. The effect of miR-206 on hexokinase 2 (HK2) expression was examined through miR-206 overexpression or miR-206 knockdown. CCK-8 assay and colony formation assay were carried out to explore the role of miR-206 on cell proliferation and colony formation, respectively. The relationship between miR-206 and HK2 was measured by dual-luciferase reporter assay. Glucose consumption, lactate production assay and ATP generation were performed in NSCLC cells following miR-206 and HK2 overexpression. We found that miR-206 was downregulated in NSCLC tissues and cells. miR-206 overexpression downregulated the expression of HK2 via targeting HK2 3′UTR in NSCLC cells. In addition, miR-206 decreased the cell viability and colony formation in NSCLC cells. Furthermore, miR-206 reduced glucose uptake, lactate production and ATP generation in NSCLC cells via HK2 repression. In conclusion, these findings suggested that miR-206 regulated NSCLC cell aerobic glycolysis by targeting HK2.

scholarly journals H19 contributes to aerobic glycolysis, proliferation and immune escape of gastric cancer cells via the miR-519d-3p/LDHA axis

2020 ◽  
Author(s):  
Linqing Sun ◽  
Juntao Li ◽  
Wenying Yan ◽  
Zhendong Yao ◽  
Ruoqin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Immune Escape ◽  
Aerobic Glycolysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Γδt Cells

Abstract Background Long non-coding RNAs (lncRNAs) have been investigated in multiple human cancers including gastric cancer (GC). Our research aims to explore the role of H19 in aerobic glycolysis, proliferation, and immune escape of GC cells.Methods The expression of H19 in GC samples were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) data, and real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Glucose consumption and lactate production were applied to assess the aerobic glycolysis of GC cells. Subcellular fractionation, luciferase reporter, and western blot assays certified the binding between genes. CCK-8 and colony formation assays were used to determine GC cell proliferation. Flow cytometry, ELISA, and RT-qPCR assays were applied to analyze the immunosuppressive effect of H19. Results H19 was highly expressed in samples of patients with GC, and associated with tumor growth in vivo. H19 knockdown suppressed glucose consumption, lactate production, proliferation of GC cells by regulating miR-519d-3p/LDHA axis. Both miR-519d-3p depletion and LDHA overexpression could reverse the H19 knockdown-induced decrease in aerobic glycolysis and proliferation. Moreover, conditioned medium (CM) from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor-associated macrophages (TAMs) in a lactate dependent manner.Conclusions The H19/miR-519d-3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells.

scholarly journals Energy metabolism in pig oocytes and early embryos

Reproduction ◽  
2003 ◽  
pp. 197-204 ◽  
Author(s):  
RG Sturmey ◽  
HJ Leese
Keyword(s):  
Embryo Development ◽  
In Vitro Maturation ◽  
Tricarboxylic Acid Cycle ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Blastocyst Stage ◽  
Early Embryo ◽  
Vitro Fertilization ◽  
Triglyceride Content

Pig oocytes and embryos differ from those of other species in having a large quantity of endogenous lipid, a potential role for which has yet to be identified. In the present study, the hypothesis that endogenous triglyceride acts as a metabolic substrate during in vitro maturation and early embryo development was tested. Embryos were produced by in vitro fertilization (IVF) of in vitro-matured, abattoir-derived immature oocytes, cultured in medium NCSU23 up to the blastocyst stage. The triglyceride content of single oocytes and embryos was measured throughout development. Oxygen and glucose consumption and the formation of lactate were measured non-invasively over the same period, enabling total ATP production to be calculated. The triglyceride content of oocytes before maturation (135+/-4.9 ng) decreased by 13 ng (P<0.05) during in vitro maturation, but there was no apparent change in triglyceride content during embryo development (117.68 ng). Oxygen consumption was low throughout embryo cleavage before reaching a peak at the blastocyst stage (P<0.01), a pattern similar to that seen in other mammals studied. Glucose consumption and lactate production were also at a maximum at the blastocyst stage (P<0.05). These data indicate that pig oocytes may use endogenous triglyceride as an energy source during in vitro maturation and that most (91-97%) of the ATP produced during embryo development comes from oxidative phosphorylation. The high exogenous glucose concentration in NCSU23 (5.5 mmol l(-1)) may be needed to form pyruvate, which in turn, produces oxaloacetate, which is required to prime the tricarboxylic acid cycle. However, the reason for the high lipid content in early pig embryos remains to be elucidated.

scholarly journals S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer

2020 ◽  
Vol 8 ◽  
Author(s):  
Yan Li ◽  
Xiao-Yu Li ◽  
Li-Xiang Li ◽  
Ru-Chen Zhou ◽  
Yinhe Sikong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Mtor Signaling ◽  
Gene Set Enrichment Analysis ◽  
Mtor Signaling Pathway ◽  
Malignant Growth

S100 calcium-binding protein A10 (S100A10) is crucially involved in the tumorigenesis of multiple malignant tumors. Reprogrammed glucose metabolism is emerging as a hallmark of various human cancers. However, the function of S100A10 in aerobic glycolysis is unclear. The expression of S100A10 was analyzed using the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and the UALCAN cancer database. Prognostic analysis was performed using the Kaplan–Meier Plotter. The correlation between S100A10 and key glycolytic factors was assessed by GEPIA. The glycolysis level was examined by determining glucose consumption, lactate production, adenosine triphosphate production, cellular oxygen consumption rate, and extracellular acidification rate. Cell apoptosis was investigated by flow cytometry. Colony formation and BrdU assays were performed to detect cell proliferation. A subcutaneous xenograft mouse model was established to evaluate the effects of S100A10 in vivo. Gene Set Enrichment Analysis and western blotting were performed to explore the downstream signaling pathway. S100A10 was significantly upregulated in gastric cancer. Its expression was associated with poor survival. S100A10 increased glucose consumption, lactate production, and the switch from oxidative phosphorylation to aerobic glycolysis. S100A10 promoted malignant proliferation and suppressed cell apoptosis in gastric cancer. S100A10 activated the mTOR pathway by interacting with annexin A2 (ANXA2) to accelerate tumor glycolysis, resulting in tumor malignant progression. S100A10 contributed to aerobic glycolysis and accelerated malignant growth by modulating the Src/ANXA2/AKT/mTOR signaling pathway. Thus, S100A10 may have pivotal roles in gastric cancer.

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