scholarly journals Zuo Gui Wan Alters Expression of Energy Metabolism Genes and Prevents Cell Death in High-Glucose Loaded Mouse Embryos

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Qi Liang ◽  
Zhipeng Qu ◽  
Yu Liang ◽  
QianJin Feng ◽  
Xin Niu ◽  
...  
Keyword(s):  
Cell Death ◽  
Energy Metabolism ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Tricarboxylic Acid Cycle ◽  
Sugar Metabolism ◽  
Embryonic Cell ◽  
Mouse Embryos ◽  
Cell Stage ◽  
Mitochondrial Energy Metabolism

Background. Zuo Gui Wan (ZGW) is a classic formula in traditional chinese medicine (TCM). Previous studies have shown that it is beneficial for impaired glucose tolerance (IGT) of adults and the offspring as well. This study aimed to understand the molecular mechanisms of the efficacy of ZGW on IGT. Methods. We used high-glucose loaded 2-cell stage mouse embryos as a model and took advantage of single-cell RNA sequencing technology to analyze the transcriptome of the model with or without ZGW. Differential gene expression analysis was performed with DESeq2. Results. High glucose can downregulate genes in the ribosome pathway, while ZGW can reverse this inhibition and as a result prevent embryo cell death caused by high glucose. Furthermore, high glucose can affect sugar metabolism and influence mitochondrial function, but ZGW can promote sugar metabolism via the tricarboxylic acid cycle mainly through upregulating the genes in the respiratory chain and oxidative phosphorylation. Conclusions. ZGW had a protective effect on embryonic cell death caused by glucose loading. The reversion of inhibition of ribosome pathway and regulation of mitochondrial energy metabolism are main effects of ZGW on high-glucose loaded embryos. This research not only revealed the global gene regulation changes of high glucose affecting 2-cell stage embryos but also provided insight into the potential molecular mechanisms of ZGW on the IGT model.

MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

2011 ◽  
Vol 256 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Nidhi Dwivedi ◽  
Ashish Mehta ◽  
Abhishek Yadav ◽  
B.K. Binukumar ◽  
Kiran Dip Gill ◽  
...  
Keyword(s):  
Cell Death ◽  
Energy Metabolism ◽  
Apoptotic Cell ◽  
Arsenic Exposure ◽  
Apoptotic Cell Death ◽  
Mitochondrial Energy Metabolism

Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics

2007 ◽  
Vol 292 (6) ◽  
pp. C2004-C2020 ◽  
Author(s):  
My-Hanh T. Nguyen ◽  
S. J. Dudycha ◽  
M. Saleet Jafri
Keyword(s):  
Energy Metabolism ◽  
Energy Production ◽  
Hydrogen Exchange ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Calcium Dynamics ◽  
Mitochondrial Energy Metabolism ◽  
Acid Cycle ◽  
Atp Production ◽  
Sodium Hydrogen

The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed “parallel activation”. To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F1F0-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F1F0-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased.

scholarly journals The role of glucose and pyruvate transport in regulating nutrient utilization by preimplantation mouse embryos

Development ◽  
1988 ◽  
Vol 104 (3) ◽  
pp. 423-429
Author(s):  
D.K. Gardner ◽  
H.J. Leese
Keyword(s):  
Glucose Uptake ◽  
Kinetic Studies ◽  
Nutrient Utilization ◽  
Embryonic Cell ◽  
Mouse Embryos ◽  
Facilitated Diffusion ◽  
Cell Stage ◽  
Analytical Technique ◽  
Preimplantation Mouse Embryos ◽  
Preimplantation Mouse

Preimplantation mouse embryos utilize pyruvate preferentially during the early cleavage stages before switching to glucose at around the time of compaction. This switch in substrate preference has been studied using a non-invasive ultramicrofluorometric analytical technique on single mouse embryos. On the basis of transport kinetic studies and inhibition by phloretin, cytochalasin B and sugar analogues, a component of glucose uptake by mouse blastocysts was found to be mediated by facilitated diffusion. The Jmax and Kt of this facilitated component were 3.53 pmol embryo-1 h-1 and 0.14 mM, respectively. At physiological concentrations of glucose, the facilitated component accounts for around 75% of glucose uptake. Glucose uptake by blastocysts was found to be insensitive to insulin, added at a range of concentrations. There was no evidence for glucose active transport. The carrier-mediated component of glucose entry was detectable from the 2-cell stage onwards. Pyruvate uptake was also mediated by a carrier throughout development. In the absence of glucose in the incubation medium, the characteristic decline in pyruvate uptake does not occur. The data are consistent with a role for embryonic cell transport in regulating glucose utilization prior to compaction, but do not exclude the involvement of metabolic factors, such as the allosteric regulation of the enzymes hexokinase and phosphofructokinase.

scholarly journals Truncating PKHD1 and PKD2 mutations alter energy metabolism

2019 ◽  
Vol 316 (3) ◽  
pp. F414-F425 ◽  
Author(s):  
Phillip Chumley ◽  
Juling Zhou ◽  
Sylvie Mrug ◽  
Balu Chacko ◽  
John M. Parant ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Gene Mutations ◽  
Mitochondrial Morphology ◽  
Polycystic Kidney ◽  
Extracellular Acidification ◽  
In Vivo Models ◽  
Mitochondrial Energy Metabolism ◽  
Hek 293

Deficiency in polycystin 1 triggers specific changes in energy metabolism. To determine whether defects in other human cystoproteins have similar effects, we studied extracellular acidification and glucose metabolism in human embryonic kidney (HEK-293) cell lines with polycystic kidney and hepatic disease 1 ( PKHD1) and polycystic kidney disease (PKD) 2 ( PKD2) truncating defects along multiple sites of truncating mutations found in patients with autosomal recessive and dominant PKDs. While neither the PKHD1 or PKD2 gene mutations nor their position enhanced cell proliferation rate in our cell line models, truncating mutations in these genes progressively increased overall extracellular acidification over time ( P < 0.001 for PKHD1 and PKD2 mutations). PKHD1 mutations increased nonglycolytic acidification rate (1.19 vs. 1.03, P = 0.002), consistent with an increase in tricarboxylic acid cycle activity or breakdown of intracellular glycogen. In addition, they increased basal and ATP-linked oxygen consumption rates [7.59 vs. 5.42 ( P = 0.015) and 4.55 vs. 2.98 ( P = 0.004)]. The PKHD1 and PKD2 mutations also altered mitochondrial morphology, resembling the effects of polycystin 1 deficiency. Together, these data suggest that defects in major PKD genes trigger changes in mitochondrial energy metabolism. After validation in in vivo models, these initial observations would indicate potential benefits of targeting energy metabolism in the treatment of PKDs.

scholarly journals Mitigation of Glucolipotoxicity-Induced Apoptosis, Mitochondrial Dysfunction, and Metabolic Stress by N-Acetyl Cysteine in Pancreatic β-Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 239 ◽  
Author(s):  
Arwa Alnahdi ◽  
Annie John ◽  
Haider Raza
Keyword(s):  
Energy Metabolism ◽  
Palmitic Acid ◽  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
High Energy ◽  
Metabolic Adaptation ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Mitochondrial Energy Metabolism ◽  
Acetyl Cysteine

Glucolipotoxicity caused by hyperglycemia and hyperlipidemia are the common features of diabetes-induced complications. Metabolic adaptation, particularly in energy metabolism; mitochondrial dysfunction; and increased inflammatory and oxidative stress responses are considered to be the main characteristics of diabetes and metabolic syndrome. However, due to various fluctuating endogenous and exogenous stimuli, the precise role of these factors under in vivo conditions is not clearly understood. In the present study, we used pancreatic β-cells, Rin-5F, to elucidate the molecular and metabolic changes in glucolipotoxicity. Cells treated with high glucose (25 mM) and high palmitic acid (up to 0.3 mM) for 24 h exhibited increased caspase/poly-ADP ribose polymerase (PARP)-dependent apoptosis followed by DNA fragmentation, alterations in mitochondrial membrane permeability, and bioenergetics, accompanied by alterations in glycolytic and mitochondrial energy metabolism. Our results also demonstrated alterations in the expression of mammalian target of rapamycin (mTOR)/5′ adenosine monophosphate-activated protein kinase (AMPK)-dependent apoptotic and autophagy markers. Furthermore, pre-treatment of cells with 10 mM N-acetyl cysteine attenuated the deleterious effects of high glucose and high palmitic acid with improved cellular functions and survival. These results suggest that the presence of high energy metabolites enhance mitochondrial dysfunction and apoptosis by suppressing autophagy and adapting energy metabolism, mediated, at least in part, via enhanced oxidative DNA damage and mTOR/AMPK-dependent cell signaling.

In vitro manipulation of early mouse embryos induces HIV1-LTRlacZ transgene expression

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1293-1300 ◽  
Author(s):  
M. Vernet ◽  
C. Cavard ◽  
A. Zider ◽  
P. Fergelot ◽  
G. Grimber ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Molecular Mechanisms ◽  
Constitutive Expression ◽  
Mouse Embryos ◽  
Lacz Gene ◽  
Cell Stage ◽  
Early Mouse ◽  
Transgenic Embryos

We report here that the transcriptional activity of early mouse embryos is affected by their manipulation and culture in vitro, using transgenic embryos that express the reporter gene lacZ. We examined the pattern of expression of the lacZ gene fused to the human immunodeficiency virus type 1 long terminal repeat during the preimplantation stages. Transgene expression is induced as early as the two-cell stage in embryos developed in vitro, while there is no constitutive expression at the same stage in embryos developed in vivo. We have established a relation between this inducible expression occurring in vitro and an oxidative stress phenomenon. Indeed, when the culture medium is supplemented with antioxidants such N-acetyl-cysteine or CuZn-superoxide dismutase the transgene expression is markedly reduced. We also present evidence that the transgene expression in vitro coincides with the onset of the embryonic genome activation as attested by the synthesis of the 70 × 10(3) M(r) protein complex. Therefore, this transgene expression could prove to be a useful tool in our understanding of the molecular mechanisms involved in this crucial developmental event.

scholarly journals Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy

2005 ◽  
Vol 25 (23) ◽  
pp. 10261-10272 ◽  
Author(s):  
Nicholas Joza ◽  
Gavin Y. Oudit ◽  
Doris Brown ◽  
Paule Bénit ◽  
Zamaneh Kassiri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Energy Metabolism ◽  
Respiratory Chain ◽  
Muscle Atrophy ◽  
Mitochondrial Respiration ◽  
Heart Function ◽  
Skeletal Muscle Atrophy ◽  
Mitochondrial Energy Metabolism ◽  
Apoptosis Inducing Factor

ABSTRACT Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein implicated in programmed cell death, plays a role in mitochondrial respiration. However, the in vivo consequences of AIF-regulated mitochondrial respiration resulting from a loss-of-function mutation in Aif are not known. Here, we report tissue-specific deletion of Aif in the mouse. Mice in which Aif has been inactivated specifically in cardiac and skeletal muscle exhibit impaired activity and protein expression of respiratory chain complex I. Mutant animals develop severe dilated cardiomyopathy, heart failure, and skeletal muscle atrophy accompanied by lactic acidemia consistent with defects in the mitochondrial respiratory chain. Isolated hearts from mutant animals exhibit poor contractile performance in response to a respiratory chain-dependent energy substrate, but not in response to glucose, supporting the notion that impaired heart function in mutant animals results from defective mitochondrial energy metabolism. These data provide genetic proof that the previously defined cell death promoter AIF has a second essential function in mitochondrial respiration and aerobic energy metabolism required for normal heart function and skeletal muscle homeostasis.

scholarly journals RIP3 mediates TCN-induced necroptosis through activating mitochondrial metabolism and ROS production in apoptosis-resistant cancer cells

2020 ◽  
Author(s):  
Xu Zhao ◽  
Jing Quan ◽  
Yue Tan ◽  
Ying Liu ◽  
Chaoliang Liao ◽  
...  
Keyword(s):  
Cell Death ◽  
Energy Metabolism ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Permeability ◽  
Ros Production ◽  
Anticancer Activities ◽  
Independent Manner ◽  
Mitochondrial Energy Metabolism ◽  
Chemotherapeutic Sensitivity

Abstract Background: Resisting cell death is one of the hallmarks of cancer. Necroptosis is a form of non-caspase dependent necrotic cell death mediated by receptor-interacting protein kinase-1/3 (RIP1/3), which represents another mode of programmed cell death besides apoptosis. Growing evidence supports that RIP3 has emerged as a critical regulator of necroptosis and can be activated by several stimuli to trigger necroptotic cell death in a RIP1-independent manner. RIP3 also acts as an energy metabolism regulator associated with switching cell death from apoptosis to necroptosis. Natural products provide a unique source for the discovery of innovative leading compounds and drugs, which exhibits promising anticancer activities through inducing cell death and enhancing chemotherapeutic sensitivity. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes and shows potent anti-tumor bioactivity. However, the underlying mechanism is not fully understood.Methods: Cell permeability assay and transmission electron microscopy were applied to identify the death pattern induced by TCN in apoptotic-resistant cancer cells. We used Seahorse extracellular flux analyzer to examine the cellular oxygen consumption rate (OCR) and flow cytometry to detect mitochondrial reactive oxygen species (ROS) content. Xenograft animal experiment was performed to assess the effect of TCN synergized with cisplatin to enhance chemotherapeutic sensitivity of tumor cells. Results: Our current findings revealed that RIP3 mediated TCN-induced necroptosis through activating mitochondria energy metabolism and ROS production in apoptotic-resistant cancer cells. RIP3 might be involved in sensitizing tumor cells to chemotherapy induced by TCN. Conclusions: Activating RIP3 to induce necroptosis through reprogramming mitochondrial energy metabolism and ROS production contributes to the anti-tumor activity of TCN. Moreover, TCN could be exploited for therapeutic gain through up-regulating RIP3 to sensitize cancer chemotherapy.

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