O-039 Mitochondrial ATP generation in mammalian eggs and Ca2+ signaling

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Swann
Keyword(s):  
Developmental Biology ◽  
Human Reproduction ◽  
Acid Oxidation ◽  
Atp Level ◽  
Atp Production ◽  
Atp Levels ◽  
Insp3 Receptors ◽  
Atp Generation ◽  
The Difference ◽  
Mouse Eggs

Abstract text In metaphase II arrested mammalian oocytes (eggs) and cleavage stage embryos the mitochondria are responsible for nearly all ATP production because glycolysis is inactivated. Luciferase assays show that ATP levels in eggs are strictly dependent upon pyruvate and fatty acid oxidation. The level of ATP in eggs appears to be maximal in conventional medium because the addition of extra mitochondrial substrates to eggs does not increase cytosolic ATP. The only clear elevation of ATP is seen at fertilization and is associated with sperm induced Ca2+ oscillations. Our recent findings suggest that the level of ATP modulates events at fertilization. At fertilization, the egg is activated by sperm derived PLCzeta which triggers a series of Ca2+ oscillations, with each Ca2+ release event causes by inositol trisphosphate (InsP3). Previous studies have shown that mouse eggs are more sensitive to PLCzeta, and generate higher frequency Ca2+ oscillations, than human eggs. Mouse eggs also generate Ca2+ oscillations and activate in response to Sr2+ that directly stimulates InsP3 receptors. In contrast, human eggs that contain the same type of InsP3 receptors do not generate Ca2+ oscillations in response to Sr2+. The difference in sensitivity of Ca2+ release between species can be explained by the fact that mouse eggs are about ten times more sensitive to InsP3 than human eggs. The reason for this difference appears to be due to ATP. The ATP level in unfertilized mouse eggs is about twice that in human eggs. Furthermore, the ability of mouse eggs to Sr2+ medium can be abolished by removing the mitochondrial substrate pyruvate, which reduces the ATP level. Adding back pyruvate to such eggs restores ATP levels promotes Sr2+ induced Ca2+ levels in mouse eggs. These data suggest that the level of ATP, possibly as ATP4-, modulates the sensitivity of the InsP3 receptor and the ability of eggs to generate Ca2+ oscillations. The level of cytosolic ATP may represent a significant ‘egg factor’ in determining the success of fertilization in humans. Enhancing mitochondrial ATP production could be useful in improving activation and embryo development after fertilization, or after artificial egg activation. References: Dumollard et al. (2009) Seminar in Cell and Developmental Biology 20, 346-353 Campbell and Swann (2006) Developmental Biology 298, 225-233 Storey et al. (2021) Molecular Human Reproduction 27, gaaa086

Heparin from Intestine and Lung Source Administered in Large Dose to Dogs with Acute Myocardial Ischemia

1978 ◽  
Vol 40 (02) ◽  
pp. 407-417
Author(s):  
Michael J Saliba ◽  
Richard J Pavalec
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Adenosine Triphosphate ◽  
Intestinal Mucosa ◽  
Large Dose ◽  
Acute Myocardial Ischemia ◽  
Ischemic Myocardium ◽  
Atp Levels ◽  
Initial Control ◽  
The Difference

SummaryIntestinal mucosa heparin (IMH) and beef lung heparin (BLH) were infused into dogs subjected to myocardial ischemia by intermittent coronary artery occlusions. The IMH was from a mixture of beef, sheep, and pig intestinal mucosa. Initial control occlusion and recovery was followed by a second occlusion with 60,000 units of IMH or BLH added. Electrocardiographic S-T segment elevations (ST) were measured acutely. There were no significant differences in ST in non-ischemic myocardium before occlusions or with occlusions. In ischemic myocardium, IMH significantly lowered control ST 84% in amount (t = 6.1 p <0.00005), and 76% in number (t = 11.6 p <0.00001). BLH lowered control ST a significant, lesser, 36% in amount (t = 3.6 p <0.008), and 35% in number (t = 3.2 p <0.01). The difference between IMH and BLH in ischemic myocardium was a significant 48% in amount (t = 4.0 p <0.0007), and 41% in number (t = 2.0 p <0.06). Myocardial adenosine triphosphate (ATP) levels were assayed after 90 min. ATP levels were 31% higher in both ischemic and non-ischemic myocardium in IMH-treated dogs than in BLH- treated. It was concluded that IMH and BLH are functionally different, and IMH was significantly more effective.

scholarly journals The role of ATP in the differential ability of Sr2+ to trigger Ca2+ oscillations in mouse and human eggs

2021 ◽  
Author(s):  
Anna Storey ◽  
Khalil Elgmati ◽  
Yisu Wang ◽  
Paul Knaggs ◽  
Karl Swann
Keyword(s):  
Phospholipase C ◽  
Egg Activation ◽  
Apparent Difference ◽  
Free Medium ◽  
Inositol 1 ◽  
Atp Levels ◽  
Mature Mouse ◽  
Differential Ability ◽  
Mouse Eggs

Abstract At fertilization in mice and humans, the activation of the egg is caused by a series of repetitive Ca2+ oscillations which are initiated by phospholipase-C(zeta)ζ that generates inositol-1-4-5-trisphophate (InsP3). Ca2+ oscillations and egg activation can be triggered in mature mouse eggs by incubation in Sr2+ containing medium, but this does not appear to be effective in human eggs. Here we have investigated the reason for this apparent difference using mouse eggs, and human eggs that failed to fertilize after IVF or ICSI. Mouse eggs incubated in Ca2+-free, Sr2+-containing medium immediately underwent Ca2+ oscillations but human eggs consistently failed to undergo Ca2+ oscillations in the same Sr2+ medium. We tested the InsP3-receptor (IP3R) sensitivity directly by photo-release of caged InsP3 and found that mouse eggs were about 10 times more sensitive to InsP3 than human eggs. There were no major differences in the Ca2+ store content between mouse and human eggs. However, we found that the ATP concentration was consistently higher in mouse compared to human eggs. When ATP levels were lowered in mouse eggs by incubation in pyruvate-free medium, Sr2+ failed to cause Ca2+ oscillations. When pyruvate was added back to these eggs, the ATP levels increased and Ca2+ oscillations were induced. This suggests that ATP modulates the ability of Sr2+ to stimulate IP3R-induced Ca2+ release in eggs. We suggest that human eggs may be unresponsive to Sr2+ medium because they have a lower level of cytosolic ATP.

scholarly journals TAMI-35. AUTOPHAGY MEDIATED LIPID CATABOLISM FACILITATES GLIOMA PROGRESSION TO OVERCOME BIOENERGETIC CRISIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii220-ii220
Author(s):  
Chenran Wang ◽  
Michael Haas ◽  
Syn Yeo ◽  
Ritama Paul ◽  
Fuchun Yang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Strong Association ◽  
Glioma Cells ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Atp Production ◽  
Lipid Catabolism ◽  
Mtorc1 Signaling

Abstract Activation of mTORC1 plays a significant role in cancer development and progression. However, the metabolic mechanisms to sustain mTORC1 activation in stressed cancer cells are still underappreciated. Autophagy, one downstream process of mTORC1, is proposed to be suppressed under the condition of mTORC1 hyper-activation. Interestingly, we recently revealed higher autophagy activity in various Tsc-deficient tumor cells with mTORC1 hyper-activity. Nevertheless, the functions and mechanisms of autophagy in regulating mTORC1 in cancer cells are not well understood. In this study, we revealed a strong association of altered mRNA levels in mTORC1 upstream and downstream genes with poor prognosis of glioma patients. Our metabolic and molecular studies indicated that autophagy mediated lipid catabolism was essential to sustain mTORC1 activity in glioma cells under energy stresses. We found that autophagy inhibitors or fatty acid oxidation (FAO) inhibition in combination with 2-Deoxy-D-glucose (2DG) decreased oxidative phosphorylation, ATP production, mTORC1 activity, and survival of glioma cells in vitro. Consistently, the combination of chloroquine (CQ) or FAO inhibitors with 2DG effectively suppressed the progression of xenografted glioma with mTORC1 hyperactivation in mice. This study established a novel autophagy/lipid degradation/FAO/ATP pathway that maintains high mTORC1 signaling and tumor progression in brain cancer cells under energy stresses. The requirement of lipophagy in brain cancers may provide an opportunity to develop new molecular therapeutic targets to counteract mTORC1 for tumor progression.

A Comparison of Transmitter and Synephrine on Luminescence Induction in the Firefly Larva

1972 ◽  
Vol 57 (3) ◽  
pp. 737-743
Author(s):  
ALBERT D. CARLSON
Keyword(s):  
Monoamine Oxidase ◽  
Extinction Rate ◽  
Pharmacological Effects ◽  
Response Latencies ◽  
Atp Production ◽  
Two Agents ◽  
Oxidase Enzyme ◽  
The Difference

1. The pharmacological effects of neural transmitter and synephrine are compared with respect to induction of luminescence in extirpated larval firefly lanterns. 2. Transmitter and synephrine show many similarities of action. They are as follows: (a) They both act directly on the lantern. (b) Their response latencies are relatively constant. (c) Both stimulate ATP production. (d) Neither induces a persistent intermediate in anoxic lanterns. (e) No monoamine oxidase enzyme appears to act on them. (f) The luminescence-inducing action of both is rapidly blocked by chlorpromazine. (g) They show identical responses in the presence of dichloroisoproterenol. 3. Luminescence induced by transmitter is much more rapidly extinguished than that induced by syneprine. 4. The possible reasons for the difference in luminescence extinction rate between the two agents are discussed and their different modes of delivery are emphasized.

scholarly journals EFFECTS OF CORTISOL ON CULTURED RAT HEART CELLS

1973 ◽  
Vol 57 (1) ◽  
pp. 109-116 ◽  
Author(s):  
J. V. Anastasia ◽  
R. L. McCarl
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Fatty Acid Oxidation ◽  
Growth Medium ◽  
Rat Heart ◽  
Acid Oxidation ◽  
Heart Cells ◽  
Atp Production ◽  
Rat Heart Cells

This paper reports the determination of the ability of rat heart cells in culture to release [14C]palmitate from its triglyceride and to oxidize this fatty acid and free [14C]palmitate to 14CO2 when the cells are actively beating and when they stop beating after aging in culture. In addition, the levels of glucose, glycogen, and ATP were determined to relate the concentration of these metabolites with beating and with cessation of beating. When young rat heart cells in culture are actively beating, they oxidize free fatty acids at a rate parallel with cellular ATP production. Both fatty acid oxidation and ATP production remain constant while the cells continue to beat. Furthermore, glucose is removed from the growth medium by the cells and stored as glycogen. When cultured cells stop beating, a decrease is seen in their ability to oxidize free fatty acids and to release them from their corresponding triglycerides. Concomitant with decreased fatty acid oxidation is a decrease in cellular levels of ATP until beating ceases. Midway between initiation of cultures and cessation of beating the cells begin to mobilize the stored glycogen. When the growth medium is supplemented with cortisol acetate and given to cultures which have ceased to beat, reinitiation of beating occurs. Furthermore, all decreases previously observed in ATP levels, fatty acid oxidation, and esterase activity are restored.

Mitochondrial function in the presence of myoglobin

1982 ◽  
Vol 53 (5) ◽  
pp. 1116-1124 ◽  
Author(s):  
R. P. Cole ◽  
P. C. Sukanek ◽  
J. B. Wittenberg ◽  
B. A. Wittenberg
Keyword(s):  
Oxygen Consumption ◽  
Steady State ◽  
Liquid Phase ◽  
Gas Phase ◽  
Oxygen Pressure ◽  
Oxygen Electrode ◽  
Oxygen Binding ◽  
Atp Production ◽  
Skeletal Muscle Mitochondria ◽  
The Difference

The effect of myoglobin on oxygen consumption and ATP production by isolated rat skeletal muscle mitochondria was studied under steady-state conditions of oxygen supply. A method is presented for the determination of steady-state oxygen consumption in the presence of oxygen-binding proteins. Oxygen consumed in suspensions of mitochondria was replenished continuously by transfer from a flowing gas phase. Liquid-phase oxygen pressure was measured with an oxygen electrode; the gas-phase oxygen concentration was held constant at a series of fixed values. Oxygen consumption was determined from the characteristic response time of the system and the difference in the steady-state gas- and liquid-phase oxygen concentrations. ATP production was determined from the generation of glucose 6-phosphate in the presence of hexokinase. During steady-state mitochondrial oxygen consumption, the oxygen pressure in the liquid phase is enhanced when myoglobin is present. Functional myoglobin present in the solution had no effect on the relation of mitochondrial respiration and ATP production to liquid-phase oxygen pressure. Myoglobin functions in this system to enhance the flux of oxygen into the myoglobin-containing phase. Myoglobin may function in a similar fashion in muscle by increasing oxygen flux into myocytes.

scholarly journals Phenylalanine requirement in children with classical PKU determined by indicator amino acid oxidation

2002 ◽  
Vol 283 (6) ◽  
pp. E1249-E1256 ◽  
Author(s):  
Glenda Courtney-Martin ◽  
Rachelle Bross ◽  
Mahroukh Raffi ◽  
Joe T. R. Clarke ◽  
Ronald O. Ball ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Oxidation ◽  
Phenylalanine Concentration ◽  
Two Phase ◽  
Amino Acid Oxidation ◽  
Blood Phenylalanine ◽  
Plasma Phenylalanine ◽  
Crossover Analysis ◽  
The Mean ◽  
The Difference

Dietary restriction of phenylalanine is the main treatment for phenylketonuria (PKU), and current estimates of requirements are based on plasma phenylalanine concentration and growth. The present study aimed to determine more precisely the phenylalanine requirements in patients with the disease by use of indicator amino acid oxidation, withl-[1-13C]lysine as the indicator. Breath13CO2 production (F13 co 2) was used as the end point. Finger-prick blood samples were also collected for measurement of phenylalanine to relate phenylalanine intake to blood phenylalanine levels. The mean phenylalanine requirement, estimated using a two-phase linear regression crossover analysis, was 14 mg · kg−1 · day−1, and the safe population intake (upper 95% confidence interval of the mean) was found to be 19.5 mg · kg−1 · day−1. A balance between phenylalanine intake and the difference between fed and fasted blood phenylalanine concentration was observed at an intake of 20 mg · kg−1 · day−1. The similarity between these two values (19.5 and 20 mg · kg−1 · day−1) suggests that the maximal phenylalanine intake for children with PKU should be no higher than 20 mg · kg−1 · day−1.

Abstract 14459: The Cardioprotective Effect on Energy Metabolism of Empagliflozin in Heart of Type 2 Diabetes Model Mouse in vivo

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masamichi Yamamoto ◽  
Yuichirou Kitai ◽  
Shigenori Yamamoto ◽  
Michael P Pieper ◽  
Yutaro Kotobuki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Placebo Group ◽  
Energy Metabolism ◽  
Treated Group ◽  
Atp Level ◽  
Intracellular Atp ◽  
Atp Levels

Chronic pathological conditions, such as type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodelling energy metabolic pathways and impairing cardiac contractility. The major source of myocardial energetics has been reported to shifts from OXPHOS in normal conditions to glycolysis in heart failure. Therefore, we decided to focus on the effect of empagliflozin on energy metabolic status in the heart.Recently, we generated two types of transgenic mice to monitor energy metabolism, intracellular ATP levels (iATP Tg) and mitochondrial ATP levels (mATP Tg) using FRET biosensor “ATeam” in the whole body, organ, and cellular levels as well as in beating heart. We intercrossed these mice with db/db, a mouse model of type 2 diabetes, and examined the energy metabolism of the heart in the empagliflozin -treated or non-treated groups.db/db;iATP Tg mice were fed EMPA-containing diets (30 mg/kg b.w., day) from 7 weeks of age for 10 weeks, and the ATP levels in the heart were measured by imaging with a fluorescence microscope. The results showed that, unlike the lowered ATP levels in the placebo group, the intracellular ATP level in the heart was significantly increased in the empagliflozin-treated group. Also, the ATP level was recovered in this empagliflozin-treated group to the same level as the wild type.Next, 8 weeks-old db/db;mATP Tg mice received a single dose of empagliflozin (30 mg/kg b.w.) via oral gavage after 4 hr of fasting. After another 3 hr of fasting, monitor the mitochondrial ATP level of the heart in vivo under the fluorescent microscope. The results showed that, unlike the placebo group, the ATP level in the mitochondria of the heart was significantly increased in the empagliflozin-treated group.These results suggest that empagliflozin may restore normal remodelling of energy metabolism in type 2 diabetic hearts.

scholarly journals Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Atp Production ◽  
Mitochondrial Fatty Acid ◽  
Mitochondrial Oxidation ◽  
Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

scholarly journals Metabolic Plasticity of Astrocytes and Aging of the Brain

2019 ◽  
Vol 20 (4) ◽  
pp. 941 ◽  
Author(s):  
Mitsuhiro Morita ◽  
Hiroko Ikeshima-Kataoka ◽  
Marko Kreft ◽  
Nina Vardjan ◽  
Robert Zorec ◽  
...  
Keyword(s):  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Acid Oxidation ◽  
Normal Brain ◽  
Atp Production ◽  
Metabolic Plasticity ◽  
Neuronal Synapses ◽  
Age Related ◽  
Pathologic Processes ◽  
The Brain

As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions. In astrocytes, glycolysis and glycogenesis are regulated by noradrenaline and insulin, respectively, while mitochondrial ATP production and fatty acid oxidation are influenced by the thyroid hormone. These regulations are essential for maintaining normal brain activities, and impairments of these processes may lead to neurodegeneration and cognitive decline. Metabolic plasticity is also associated with (re)activation of astrocytes, a process associated with pathologic events. It is likely that the recently described neurodegenerative and neuroprotective subpopulations of reactive astrocytes metabolize distinct energy substrates, and that this preference is supposed to explain some of their impacts on pathologic processes. Importantly, physiologic and pathologic properties of astrocytic metabolic plasticity bear translational potential in defining new potential diagnostic biomarkers and novel therapeutic targets to mitigate neurodegeneration and age-related brain dysfunctions.

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