Endocrine and amino acid regulation of liver macroautophagy and proteolytic function

1994 ◽  
Vol 266 (1) ◽  
pp. G118-G122
Author(s):  
E. Bergamini ◽  
A. Del Roso ◽  
Z. Gori ◽  
P. Masiello ◽  
M. Masini ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Intraperitoneal Administration ◽  
Physiological Mechanism ◽  
Albino Rats ◽  
Sprague Dawley ◽  
Subsequent Increase ◽  
Stimulatory Agent ◽  
And Control

Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels)

Turnover of total proteins and ornithine aminotransferase during liver regeneration in rats

1980 ◽  
Vol 238 (1) ◽  
pp. E46-E52
Author(s):  
S. L. Augustine ◽  
R. W. Swick
Keyword(s):  
Amino Acids ◽  
Liver Regeneration ◽  
Protein Degradation ◽  
Partial Hepatectomy ◽  
Free Amino ◽  
Liver Protein ◽  
Ornithine Aminotransferase ◽  
Fractional Rate

The recovery of approximately 40% of the total liver protein during the first day after partial hepatectomy was shown to be due to the near cessation of protein breakdown rather than to an increase in protein synthesis. The decrease in degradation of total protein was less if rats were adrenalectomized or protein-depleted prior to partial hepatectomy. The effect of these treatments originally suggested that changes in free amino acid levels in liver might be related to the rate of protein degradation. However, no correlation was found between levels of total free amino acids and rates of breakdown. Measurements of individual amino acids during liver regeneration suggested that levels of free methionine and phenylalanine, amino acids that have been found to lower rates of protein degradation in vitro, are not correlated with rates of breakdown in vivo. The difference between the fractional rate of ornithine aminotransferase degradation (0.68/day and 0.28/day in sham-hepatectomized and partially hepatectomized rats, respectively) was sufficient to account for the higher level of this protein 3 days after surgery in the latter group.

Abstract 2838: Bone Marrow Mesenchymal Stem Cells Differentiated into Beating Cardiomyocytes In Vivo and Improved Myocardial Function

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tong Wang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Min-shan Tsai ◽  
Max Harry Weil
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Myocardial Function ◽  
Phosphate Buffer Solution ◽  
Sprague Dawley ◽  
Buffer Solution ◽  
Marrow Mesenchymal Stem Cells ◽  
And Control

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)

Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans

1992 ◽  
Vol 263 (5) ◽  
pp. E928-E934 ◽  
Author(s):  
K. S. Nair ◽  
R. G. Schwartz ◽  
S. Welle
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Essential Amino Acids ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Muscle Protein Metabolism

Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans.

Demonstration of in vivo metabolic effects of 3,5-di-iodothyronine

1996 ◽  
Vol 149 (2) ◽  
pp. 319-325 ◽  
Author(s):  
M Cimmino ◽  
F Mion ◽  
F Goglia ◽  
Y Minaire ◽  
A Géloën
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Octanoic Acid ◽  
Control Level ◽  
Metabolic Effects ◽  
Daily Energy Expenditure ◽  
Sprague Dawley ◽  
Daily Energy ◽  
And Control

Abstract The objective of the present study was to test in vivo the metabolic effects of 3,5-di-iodothyronine (3,5-T2) in unanesthetized and unrestrained male Sprague–Dawley rats. Amino acid and lipid metabolisms were investigated by breath tests using as tracers the 13C-carboxyl-labeled molecules of leucine, α-ketoisocaproic acid (KIC) and octanoic acid, in four different groups of rats: hypothyroid animals (receiving propylthiouracil (PTU) and iopanoic acid), hypothyroid animals treated with either a daily i.p. injection of 3,5-T2 (25 μg/100 g body weight), or triiodothyronine (T3) (1 μg/100 g body weight), and control euthyroid animals receiving equivalent volumes of the vehicle solutions. Energy expenditure was measured by continuous monitoring of O2 consumption and CO2 production in these different groups. Daily energy expenditure was decreased by 30% in PTU-treated rats. The chronic treatments with 3,5-T2 and T3 restored daily energy expenditure to the control level. 13CO2 recovered in breath following the i.v. injection of octanoic acid-[1-13C] was decreased in hypothyroid animals compared with control animals (P<0·05) and restored to control values by T3 and 3,5-T2 treatments. The 13CO2 recovered in breath after i.v. injection of leucine-[1-13C]was increased in PTU-treated compared with control animals (P<0·05). Chronic treatment with either 3,5-T2 or T3 restored 13CO2 to control values. Excretion of 13CO2 recovered in breath following the i.v. injection of KIC-[1-13C] was increased in PTU-treated compared with control animals. Chronic treatments with either 3,5-T2 or T3 did not restore KIC decarboxylation. These results suggest that 3,5-T2 exerts metabolic effects on energy expendi ture, on both lipid β-oxidation and leucine metabolism in hypothyroid rats. We conclude that 3,5-T2 is a metabolically active iodothyronine. Journal of Endocrinology (1996) 149, 319–325

Protein metabolism in lung. II. Influence of amino acids and glucose on protein degradation

1979 ◽  
Vol 47 (5) ◽  
pp. 1058-1061 ◽  
Author(s):  
M. J. Chiang ◽  
D. Massaro
Keyword(s):  
Amino Acids ◽  
Protein Degradation ◽  
Rat Plasma ◽  
Lung Water ◽  
Exogenous Glucose ◽  
Isolated Perfused Lung ◽  
Perfusate Flow ◽  
Perfused Lung ◽  
Normal Rat

We used the isolated perfused lung to study protein degradation. Proteins were labeled in vivo during 10 min (fast) or 5 h (slow). The absence of exogenous amino acids lowered the rate of proteolysis of fast but not of slowly turning over proteins. Addition of normal rat plasma levels of amino acids, after 45 min of perfusion without amino acids, returned the rate of proteolysis to control levels. The absence of exogenous glucose increased the rate of degration of rapidly turning over proteins but decreased the degradation rate of slowly turning over proteins. These changes took place in the absence of any measurable effect of amino acids or glucose on the amount of lung water, the rate of perfusate flow, the lung concentration of ATP or the intracellular concentration of free phenylalanine. We conclude that these substrates influence proteolysis in our system and that the degradation of rapidly and slowly turning over proteins are regulated independently in the isolated perfused lung.

Uptake of tyrosine and leucine in vivo by brain of diabetic and control rats

1984 ◽  
Vol 247 (5) ◽  
pp. C450-C453 ◽  
Author(s):  
J. T. Brosnan ◽  
R. G. Forsey ◽  
M. E. Brosnan
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Diabetic Rats ◽  
Injection Technique ◽  
Brain Uptake ◽  
Absolute Increase ◽  
Normal Plasma ◽  
Branched Chain ◽  
And Control

The uptake of tyrosine and leucine by brain of control and diabetic rats was examined using the Oldendorf intracarotid injection technique. The brain uptake indexes (BUI) for tyrosine and leucine were identical in diabetic and control rats when the injectate consisted of labeled amino acids in Krebs saline. When the injectate consisted of radioactive amino acids added to plasma from either normal or diabetic rats, there was a decreased BUI for tyrosine from diabetic plasma compared with that from normal plasma. This was evident in both control and diabetic rats. Fractional uptake of leucine was unchanged in all situations. Because leucine level is elevated in plasma of diabetic rats there is an absolute increase in leucine uptake in diabetes. Branched-chain amino acids, added to normal plasma in the concentrations at which they occur in diabetic plasma, inhibited the uptake of tyrosine to the same extent as diabetic plasma did. We conclude that the decreased brain uptake and decreased brain level of tyrosine in diabetes is due to the high circulating levels of branched-chain amino acids and cannot be attributed to intrinsic changes in the blood-brain transporter for large neutral amino acids or to changes in other constituents of plasma.

Splanchnic sequestration of amino acids in aged rats: in vivo and ex vivo experiments using a model of isolated perfused liver

2008 ◽  
Vol 294 (3) ◽  
pp. R748-R755 ◽  
Author(s):  
M. Jourdan ◽  
L. Cynober ◽  
C. Moinard ◽  
M. C. Blanc ◽  
N. Neveux ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ex Vivo ◽  
High Protein Diet ◽  
High Protein ◽  
Protein Diet ◽  
Aged Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Urea Production

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.

scholarly journals Triazine Inhibits Toxoplasma gondii Tachyzoites In Vitro and In Vivo

2005 ◽  
Vol 49 (8) ◽  
pp. 3463-3467 ◽  
Author(s):  
Ernest J. Mui ◽  
David Jacobus ◽  
Wilbur K. Milhous ◽  
Guy Schiehser ◽  
Honghue Hsu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Toxoplasma Gondii ◽  
Homo Sapiens ◽  
Intraperitoneal Administration ◽  
Development Program ◽  
Amino Acid Sequences ◽  
Peroral Administration ◽  
Mammalian Host

ABSTRACT The triazine WR99210 [4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(2,4,5-trichlorophenoxypropyloxy)-1,3,5 triazine] inhibits Toxoplasma gondii in vitro at nanomolar levels (P < 0.05). The 50% inhibitory concentration (IC50) was approximately 50 nM. It is a potent inhibitor in vitro and is also effective in vivo. Administration of WR99210 parenterally (i.e., intraperitoneally) reduced the mean number of RH strain tachyzoites present in peritoneal fluid substantially 4 days after intraperitoneal infection of mice. There was a mean of approximately 35 million parasites in control mice as contrasted with approximately 2 million parasites in mice treated with 1.25 mg WR99210/kg of body weight in a representative experiment (P < 0.05). In addition the prodrug PS-15 N′-[3-(2,4, 5-trichlorophenoxy)propyloxy]-N9-(1-methylethyl) imidocarbonimidicdiamide is converted to 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(2,4,5-trichlorophenoxypropyloxy)-1,3,5 triazine in vivo when the prodrug is administered orally. PS-15 administered by gavage also reduced intraperitoneal RH strain T. gondii tachyzoite numbers. WR99210 has high efficacy and relatively low toxicity because of its substantial effect on T. gondii dihydrofolate reductase (DHFR) but not the mammalian host DHFR. Amino acid sequences of T. gondii, Plasmodium falciparum, and Homo sapiens DHFRs were compared. It is of interest that of the DHFR amino acids considered to be interacting with WR99210 in P. falciparum within interatomic distances within 3 to 5 Å, four of eight were shared with T. gondii DHFR. H. sapiens also shared four amino acids thought to be interacting with WR99210. Efficacy of intraperitoneal administration of WR99210 and peroral administration of PS-15 demonstrate the potential usefulness of this class of compounds in treatment of toxoplasmosis administered either parenterally or perorally. The recent development program for this class of antimicrobials as antimalarials makes our proof of principle of improved efficacy of triazines (compared with the gold standard treatment, pyrimethamine) against T. gondii especially promising.

In Vivo Evaluation of Nano-HA/PDLLA Composite

2005 ◽  
Vol 284-286 ◽  
pp. 881-884 ◽  
Author(s):  
Yu Mei Xiao ◽  
Hong Song Fan ◽  
Yao Wu ◽  
Jin Rui Xu ◽  
Y. Tan ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Sem Analysis ◽  
Albino Rats ◽  
Degradation Behavior ◽  
Porous Network ◽  
In Vivo Evaluation ◽  
Good Biocompatibility ◽  
Wistar Albino Rats ◽  
And Control

The purpose of this study was to evaluate the behavior of nano-hydroxyapatite/ poly(D,L)lactide (n-HA/PDLLA) composite in vivo. The composite rods containing about 40wt% n-HA and control HA rods with a diameter of 2mm and a length of 6mm were implanted into the femora of 16 New Zealand rabbits. Composite wafers with a diameter of 5mm and a thickness of 1mm were implanted into the dorsal subcutis of 18 Wistar Albino rats. After definite intervals, the histological analysis was completed by light microscopy and the degradation behavior was observed by scanning electron microscopy. The histological analysis showed no obvious difference between n-HA /PDLLA composite and pure HA that had good biocompatibility and osteoconductivity. SEM analysis of the surface and cross section of the samples showed that the degradation of the composite started from surface, then into the inner gradually and formed multiple pores at surface. The pore size and porosity gradually increased along with time and a porous network may be formed.

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