Hepatocyte mitochondrial metabolism is inhibited in neonatal rat endotoxaemia: effects of glutamine

2002 ◽  
Vol 102 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Michele A. MARKLEY ◽  
Agostino PIERRO ◽  
Simon EATON
Keyword(s):  
Electron Microscopy ◽  
Oxygen Consumption ◽  
Wistar Rats ◽  
Atp Synthesis ◽  
Hepatic Metabolism ◽  
Mitochondrial Metabolism ◽  
Neonatal Rat ◽  
Proton Leak ◽  
Normal Appearance ◽  
Beneficial Effects

Glutamine has beneficial effects on enterocytes and the immune system in sepsis, but its effects on hepatic metabolism remain unknown. The aim of the present study was to determine the effects of glutamine on hepatocyte energy metabolism under conditions of neonatal endotoxaemia. Suckling Wistar rats were injected intraperitoneally with 200μg/kg lipopolysaccharide. Oxygen consumption was measured polarographically in hepatocytes respiring on either palmitate (0.5mM) or palmitate plus glutamine (10mM). Total hepatocyte oxygen consumption was similar in hepatocytes from control and endotoxic rats, but this was due to a decrease in intramitochondrial and an increase in extramitochondrial oxygen consumption in the cells from endotoxic animals. The addition of glutamine to hepatocytes from endotoxic rats restored intramitochondrial oxygen consumption to control levels. Although glutamine did not reverse the inhibition of the thermogenic proton leak observed in endotoxaemia, it significantly increased oxygen consumption due to mitochondrial ATP synthesis (P = 0.03). Glutamine significantly increased the hepatocyte ATP/ADP ratio (P = 0.02 compared with hepatocytes from endotoxic rats). Electron microscopy revealed morphological damage to the mitochondria of hepatocytes from endotoxic rats, and a return to a normal appearance with the addition of glutamine. We conclude that glutamine reverses the inhibition of mitochondrial metabolism that is observed in endotoxaemia. The effect is primarily at the level of ATP synthesis.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (5) ◽  
pp. 381-386 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In constrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

ConA induced changes in energy metabolism of rat thymocytes

1992 ◽  
Vol 12 (2) ◽  
pp. 109-114 ◽  
Author(s):  
F. Buttgereit ◽  
M. D. Brand ◽  
M. Müller
Keyword(s):  
Protein Synthesis ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Dna Synthesis ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Ehrlich Ascites ◽  
Activated State ◽  
Ehrlich Ascites Tumour ◽  
Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In contrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

EFFECT OF COLD ON RATS CHRONICALLY EXPOSED TO MALATHION

1962 ◽  
Vol 40 (1) ◽  
pp. 1671-1676 ◽  
Author(s):  
A. V. Marton ◽  
E. A. Sellers ◽  
W. Kalow
Keyword(s):  
Oxygen Consumption ◽  
Wistar Rats ◽  
Initial Period ◽  
High Rate ◽  
Cold Environment ◽  
Body Temperatures ◽  
Control Groups ◽  
Normal Appearance ◽  
Daily Diet ◽  
And Control

Wistar rats received 4000 p.p.m. of malathion in their daily diet without showing evidence of intoxication (normal appearance, growth, food intake). When the animals were clipped and exposed to an ambient temperature of 1.5 °C they survived for a much shorter period in the cold environment than did control animals not receiving malathion. In both experimental and control groups, deaths occurred when body temperatures had dropped to about 18 °C. During the initial period in the cold environment, animals of both groups were able to increase their oxygen consumption to the same extent. There was no indication of an increased heat loss by the malathion-treated rats. It thus appeared likely that the insecticide decreased the ability of rats to produce heat continuously over a prolonged period at a high rate. The activities of cholinesterase in plasma were reduced in the malathion-treated rats but were not affected by the cold stress.

EFFECT OF COLD ON RATS CHRONICALLY EXPOSED TO MALATHION

1962 ◽  
Vol 40 (12) ◽  
pp. 1671-1676 ◽  
Author(s):  
A. V. Marton ◽  
E. A. Sellers ◽  
W. Kalow
Keyword(s):  
Oxygen Consumption ◽  
Wistar Rats ◽  
Initial Period ◽  
High Rate ◽  
Cold Environment ◽  
Body Temperatures ◽  
Control Groups ◽  
Normal Appearance ◽  
Daily Diet ◽  
And Control

Wistar rats received 4000 p.p.m. of malathion in their daily diet without showing evidence of intoxication (normal appearance, growth, food intake). When the animals were clipped and exposed to an ambient temperature of 1.5 °C they survived for a much shorter period in the cold environment than did control animals not receiving malathion. In both experimental and control groups, deaths occurred when body temperatures had dropped to about 18 °C. During the initial period in the cold environment, animals of both groups were able to increase their oxygen consumption to the same extent. There was no indication of an increased heat loss by the malathion-treated rats. It thus appeared likely that the insecticide decreased the ability of rats to produce heat continuously over a prolonged period at a high rate. The activities of cholinesterase in plasma were reduced in the malathion-treated rats but were not affected by the cold stress.

Cellular energy utilization and molecular origin of standard metabolic rate in mammals

1997 ◽  
Vol 77 (3) ◽  
pp. 731-758 ◽  
Author(s):  
D. F. Rolfe ◽  
G. C. Brown
Keyword(s):  
Free Energy ◽  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Metabolic Rate ◽  
Atp Synthesis ◽  
Standard Metabolic Rate ◽  
Evolutionary Significance ◽  
Proton Leak ◽  
Molecular Origin

The molecular origin of standard metabolic rate and thermogenesis in mammals is examined. It is pointed out that there are important differences and distinctions between the cellular reactions that 1) couple to oxygen consumption, 2) uncouple metabolism, 3) hydrolyze ATP, 4) control metabolic rate, 5) regulate metabolic rate, 6) produce heat, and 7) dissipate free energy. The quantitative contribution of different cellular reactions to these processes is assessed in mammals. We estimate that approximately 90% of mammalian oxygen consumption in the standard state is mitochondrial, of which approximately 20% is uncoupled by the mitochondrial proton leak and 80% is coupled to ATP synthesis. The consequences of the significant contribution of proton leak to standard metabolic rate for tissue P-to-O ratio, heat production, and free energy dissipation by oxidative phosphorylation and the estimated contribution of ATP-consuming processes to tissue oxygen consumption rate are discussed. Of the 80% of oxygen consumption coupled to ATP synthesis, approximately 25-30% is used by protein synthesis, 19-28% by the Na(+)-K(+)-ATPase, 4-8% by the Ca2(+)-ATPase, 2-8% by the actinomyosin ATPase, 7-10% by gluconeogenesis, and 3% by ureagenesis, with mRNA synthesis and substrate cycling also making significant contributions. The main cellular reactions that uncouple standard energy metabolism are the Na+, K+, H+, and Ca2+ channels and leaks of cell membranes and protein breakdown. Cellular metabolic rate is controlled by a number of processes including metabolic demand and substrate supply. The differences in standard metabolic rate between animals of different body mass and phylogeny appear to be due to proportionate changes in the whole of energy metabolism. Heat is produced by some reactions and taken up by others but is mainly produced by the reactions of mitochondrial respiration, oxidative phosphorylation, and proton leak on the inner mitochondrial membrane. Free energy is dissipated by all cellular reactions, but the major contributions are by the ATP-utilizing reactions and the uncoupling reactions. The functions and evolutionary significance of standard metabolic rate are discussed.

Surface epithelial ultrastructure of the polycystic ovary in the BB wistar rat

1986 ◽  
Vol 44 ◽  
pp. 252-253
Author(s):  
R. C. Kaufmann ◽  
F. K. Khosho ◽  
K. S. Amankwah
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Wistar Rats ◽  
Polycystic Ovary ◽  
Wistar Rat ◽  
Polycystic Ovaries ◽  
Chemical Diabetes ◽  
Scanning Electron

Diabetes decreases the fertility of females, but the mechanisms are not completely understood. In our investigations, we have found that 13% of the female BB Wistar rats that spontaneously developed chemical diabetes had persistent estrous. In this study the ovaries of these rats were examined by scanning electron microscopy(SEM) and compared to normal-cycling controls as well as to rats that had developed polycystic ovaries(PCO) by exposure to constant 1ight.

Cardiac mitofusin-1 is declined in non-responding patients with idiopathic dilated cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hsiao ◽  
I Shimizu ◽  
T Wakasugi ◽  
S Jiao ◽  
T Watanabe ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Heart Failure ◽  
Ventricular Myocytes ◽  
Severe Heart Failure ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Heart Failure Patients ◽  
Underlying Mechanisms ◽  
Neonatal Rat Ventricular Myocytes ◽  
Mitofusin 1

Abstract Background/Introduction Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway negatively regulates Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients. Funding Acknowledgement Type of funding source: None

Biochemical and histopathological effects of low dose vanadium in the healing of acetic acid-induced colitis in male wistar rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tosan Peter Omayone ◽  
Samuel Babafemi Olaleye
Keyword(s):  
Acetic Acid ◽  
Untreated Control ◽  
Wistar Rats ◽  
Low Dose ◽  
Healing Process ◽  
Beneficial Effects ◽  
Male Wistar Rats ◽  
Haematological Changes ◽  
Therapeutic Properties ◽  
Histopathological Effects

Abstract Objectives Vanadium has been reported to possess relevant therapeutic properties such as anti-diabetic and anti-tumoral. This study aimed at determining the effects of vanadium on experimentally induced colitis in rats. Methods Forty-five male Wistar rats (103 ± 3.90 g, n=15) were used for this study and were divided into three groups. Group 1 (Untreated control) had nothing added to their drinking, while groups 2 and 3 received sodium metavanadate at a dose of 50 and 200 mg/L respectively in their drinking water for 10 weeks. Colitis was thereafter induced by intra colonic administration of 1.50 mL of 6% acetic acid. Animals were sacrificed on day 0 (pre-induction), three- and seven-days post induction. Blood samples were collected for haematological variables and the distal 8 cm of the colon was collected for macroscopic, histological and biochemical (malondialdehyde-MDA, superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase- GPx and nitrite concentration- NO) assessment. Results Low dose vanadium proved beneficial in ameliorating acetic acid-induced colitis by improving both histopathological and haematological changes. Gross observation showed a faster healing rate in vanadium treated groups (50 and 200 mg/L) compared with untreated control at day 3 (40 and 26.20 vs. 2.50%) and day 7 (80 and 66.70 vs. 42%) respectively. Vanadium also appears to exert its beneficial effects on acetic acid-induced colitis via up regulation of antioxidant enzymes (SOD, CAT, GPx) and NO while decreasing the over production of MDA. Conclusions Vanadium at small concentration functions as an essential trace element and may be able to promote healing process during ulcerative colitis.

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