scholarly journals Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress

2019 ◽  
Vol 30 (15) ◽  
pp. 1864-1877 ◽  
Author(s):  
Lukasz Samluk ◽  
Malgorzata Urbanska ◽  
Katarzyna Kisielewska ◽  
Karthik Mohanraj ◽  
Min-Ji Kim ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Genetic Alterations ◽  
Prolonged Treatment ◽  
Compensatory Mechanism ◽  
Antimycin A ◽  
Short Term ◽  
Mitochondrial Stress ◽  
Mtor Kinase ◽  
Inhibition Of Protein Synthesis

Previous studies demonstrated that cells inhibit protein synthesis as a compensatory mechanism for mitochondrial dysfunction. Protein synthesis can be attenuated by 1) the inhibition of mTOR kinase, which results in a decrease in the phosphorylation of S6K1 and 4E-BP1 proteins, and 2) an increase in the phosphorylation of eIF2α protein. The present study investigated both of these pathways under conditions of short-term acute and long-term mitochondrial stress. Short-term responses were triggered in mammalian cells by treatment with menadione, antimycin A, or CCCP. Long-term mitochondrial stress was induced by prolonged treatment with menadione or rotenone and expression of genetic alterations, such as knocking down the MIA40 oxidoreductase or knocking out NDUFA11 protein. Short-term menadione, antimycin A, or CCCP cell treatment led to the inhibition of protein synthesis, accompanied by a decrease in mTOR kinase activity, an increase in the phosphorylation of eIF2α (Ser51), and an increase in the level of ATF4 transcription factor. Conversely, long-term stress led to a decrease in eIF2α (Ser51) phosphorylation and ATF4 expression and to an increase in S6K1 (Thr389) phosphorylation. Thus, under long-term mitochondrial stress, cells trigger long-lasting adaptive responses for protection against excessive inhibition of protein synthesis.

Long-term regulation of hexose uptake by isoproterenol in cultured 3T3 adipocytes

1985 ◽  
Vol 248 (6) ◽  
pp. E706-E711 ◽  
Author(s):  
J. P. van Putten ◽  
H. M. Krans
Keyword(s):  
Protein Synthesis ◽  
Prolonged Exposure ◽  
Term Effect ◽  
Long Term Effects ◽  
Fat Cell ◽  
Short Term ◽  
Long Term Effect ◽  
Short Term Exposure ◽  
Hexose Uptake

Catecholamines are known to have short-term regulatory effects on fat cell hexose uptake. We examined the long-term effects of catecholamines on the insulin-sensitive 2-deoxyglucose (dGlc) uptake in cultured 3T3-L1 adipocytes. Prolonged exposure (48 h) to isoproterenol (beta-adrenergic agonist) stimulated the basal dGlc uptake up to 90%. The effect was specific, time, concentration, and protein synthesis dependent and reversible. The effect of insulin was unaltered and superimposed on the increase in basal dGlc uptake. The long-term effect of isoproterenol was mimicked by epinephrine, dibutyryl cAMP (DBcAMP), and 1-methyl-3-isobutylxanthine (IBMX). By contrast, short-term exposure to isoproterenol (and epinephrine) induced a protein synthesis-independent increase in basal dGlc uptake (30%) not accompanied by an increase in insulin responsiveness. Moreover, on short-term basis, DBcAMP and IBMX suppressed both the basal and insulin-stimulated uptake up to 50%. Determination of the intracellular nonphosphorylated dGlc during the uptake and of the hexokinase activity revealed that the long-term effect of isoproterenol was most likely due to alterations low in dGlc transport. In conclusion, long-term regulators of hexose uptake are in cultured 3T3-L1 adipocytes, isoproterenol, and other cAMP stimulators. The long-term effect is independent from the short-term regulatory effect of the agents and from the effect of insulin.

scholarly journals Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ramiro Tintorelli ◽  
Pablo Budriesi ◽  
Maria Eugenia Villar ◽  
Paul Marchal ◽  
Pamela Lopes da Cunha ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Prior Training ◽  
Short Term ◽  
Promoting Effect ◽  
Cellular Processes ◽  
Spaced Learning ◽  
Inter Trial Interval ◽  
Established Fact ◽  
Massed Learning

AbstractThe superiority of spaced over massed learning is an established fact in the formation of long-term memories (LTM). Here we addressed the cellular processes and the temporal demands of this phenomenon using a weak spatial object recognition (wSOR) training, which induces short-term memories (STM) but not LTM. We observed SOR-LTM promotion when two identical wSOR training sessions were spaced by an inter-trial interval (ITI) ranging from 15 min to 7 h, consistently with spaced training. The promoting effect was dependent on neural activity, protein synthesis and ERKs1/2 activity in the hippocampus. Based on the “behavioral tagging” hypothesis, which postulates that learning induces a neural tag that requires proteins to induce LTM formation, we propose that retraining will mainly retag the sites initially labeled by the prior training. Thus, when weak, consecutive training sessions are experienced within an appropriate spacing, the intracellular mechanisms triggered by each session would add, thereby reaching the threshold for protein synthesis required for memory consolidation. Our results suggest in addition that ERKs1/2 kinases play a dual role in SOR-LTM formation after spaced learning, both inducing protein synthesis and setting the SOR learning-tag. Overall, our findings bring new light to the mechanisms underlying the promoting effect of spaced trials on LTM formation.

Drug inhibition of memory formation in chickens II. Short-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 455-464 ◽  
Keyword(s):  
Protein Synthesis ◽  
Sodium Pump ◽  
Short Term Memory ◽  
Memory Loss ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Short Term ◽  
Synthesis Inhibitor ◽  
Term Memory

1. Memory in day-old-chickens during the first few hours after learning can be made to decline by the prior intracranial injection of two classes of drugs. 2. Sodium pump inhibitors in increasing doses cause increasingly rapid loss of memory. 3. Protein synthesis inhibitors in increasing doses attain a maximum potency in causing memory decline and the rate may not be further accelerated by higher doses. 4. Adding a sodium pump inhibitor to the inhibition of protein synthesis increases memory loss. 5. Adding a protein synthesis inhibitor to a sodium pump inhibitor causes no further loss. 6. Therefore within a few minutes of learning a short-term memory of limited time span but independent of protein synthesis becomes supplemented and eventually replaced by a long-term storage requiring protein synthesis. The amount of long-term store is set by the amount of short-term memory. 7. The short-term store could be directly dependent on post-activation enhancement of Na + extrusion from neurons. Some physiological mechanisms by which this could be achieved and how this might activate protein synthesis are discussed.

How Renal Phosphate Transport Is Regulated

Physiology ◽  
1987 ◽  
Vol 2 (2) ◽  
pp. 45-48
Author(s):  
H Murer ◽  
M Kerstin
Keyword(s):  
Protein Synthesis ◽  
Inorganic Phosphate ◽  
Apical Membrane ◽  
Phosphate Transport ◽  
Short Term ◽  
Transcellular Transport ◽  
Sodium Dependent ◽  
Transport Of Inorganic Phosphate ◽  
Cotransport System

Transcellular transport of inorganic phosphate (Pi) in the renal proximal tubule is sodium dependent. The entry step across the apical membrane involves a Na-Pi cotransport system and is subject to short-term and long-term regulation. This regulation can be protein synthesis independent (short term) as well as protein synthesis dependent (long term).

scholarly journals The Effect of Different Hormones and Antibiotics on Activity of AST Enzyme and its Isozymes in Wistar Rats

2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Minoo Azani ◽  
Asghar Moshtaghie ◽  
Ali Asghar Rastegari
Keyword(s):  
Protein Synthesis ◽  
Steroid Hormones ◽  
Aspartate Aminotransferase ◽  
Wistar Rats ◽  
Sesame Oil ◽  
Control Group ◽  
Short Term ◽  
Group 2 ◽  
Tetracycline Group

Background: One of the valuable tests for diagnosis of cardiovascular and liver diseases is measuring of AST activity. One of the main enzymes of transaminases group is aspartate aminotransferase. Previous Studies have shown that some alteration may occur in mitochondria function as the result of different disease or taking different medication; these changes in mitochondrial and cytosolic AST isozymes can be the sign of disorders. According to the role of steroid hormone in induction of its effects on protein synthesis genes, this study is conducted to shed some light on mechanisms and the interference of steroid hormones and antibiotics.Materials, Methods & Results: In this study, male Wistar rats were injected intramuscularly with Testosterone, progesterone and estradiol; while tetracycline and streptomycin injections were intraperitoneal. Testosterone, progesterone and estradiol injections were carried out in a short-term (15 days) and long-term (45 days) periods. Steroid hormones were dissolved in sesame in a way that by each injection, 0.2 mL sesame oil (containing specific amount of hormone) was injected to the rat. Control group was kept in the same condition except that their sesame oil injection contained no hormone. Tetracycline and Streptomycin injection was carried out for 5 days at 7 am and pm, at 50 mg/kg dosage intraperitoneally. In short- and long-term periods, rats were divided into four groups of 6-member. The concentrations were the same in the periods and 0.2 mL sesame oil was injected intramuscularly. 1 mg testosterone, 12 mg progesterone and 0.2 mg estradiol were intramuscularly injected to rats in group 2, 3 and 4, respectively [10]. Rats were divided into 9 six-member groups as follows: Group 1: intraperitoneal injection of 0.2 mL physiological serum; group 2: injection of 1 mg testosterone; group 3: injection of 1 mg testosterone + 50 mg/kg streptomycin; group 4: injection of 1 mg testosterone + 50 mg/kg tetracycline; group 5: injection of 0.2 mg estradiol; group 6: injection of 0.2 mg estradiol + 50 mg/kg streptomycin; group 7: injection of 0.2 mg estradiol + 50 mg/kg tetracycline; group 8: injection 50 mg/kg streptomycin; and group 9: injection of 50 mg/kg tetracycline. Serum concentration of AST enzyme was measured at the end of each period and the data were compared by SPSS software. all three steroid hormones had no significant impact on AST activity in short term. However, a significant effect was observed in long term in mean AST activities of the 4 groups. The group injected by testosterone exhibited 9% increases in comparison with the control group. Antibiotic-administrated groups showed lower activities as compared with hormone-injected groups. Steroid hormones and testosterone can enhance AST activity, in short-term and long-term, respectively by induction of protein enzyme. The second test confirmed this theory as the antibiotics decreased the AST activity enhancement by testosterone.Discussion: Based on the present study, steroid hormones can enhance the aspartate aminotransferase activity; and antibiotics can decrease the level of this liver enzyme by inhibition of polypeptide synthesis on related genes. This reaction could be due to interference of hormones and antibiotics effect which hinders the hormone effect along with the drug to activate the protein synthesis process.

Reactivation of cytoplasmic actomyosin in Physarum plasmodia extracted with glycerol and dimethylsulphoxide

1987 ◽  
Vol 87 (2) ◽  
pp. 231-239
Author(s):  
R. Bell ◽  
F. Achenbach
Keyword(s):  
Calcium Sensitivity ◽  
Inhibitory Effect ◽  
Prolonged Treatment ◽  
Short Term ◽  
Extraction Procedures ◽  
Term Extraction ◽  
Cytoplasmic Actomyosin ◽  
Structural Preservation ◽  
Physarum Plasmodia

Thin-spread plasmodia of Physarum were subjected to extraction procedures using 50% glycerol or DMSO (dimethylsulphoxide) followed by labelling of actin with fluorescent phallotoxins. During the reactivation of the actomyosin system by 2 mM-MgATP fluorescent actin fibres contract isotonically, which results in numerous fluorescent ‘contraction beads’. After short-term extraction 1 mM-Ca2+ has an inhibitory effect on the reactivation. This calcium sensitivity is abolished after long-term extraction with glycerol. Calcium at 10 mM irreversibly inhibits reactivation, irrespective of the duration of extraction. The inhibitory effect of 10 mM-calcium is prevented by phallotoxin labelling prior to incubation in Ca2+. The DMSO model shows an improvement in structural preservation when compared with the glycerol models. However, reactivation is inhibited by prolonged treatment with DMSO.

scholarly journals Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin.

1996 ◽  
Vol 40 (10) ◽  
pp. 2271-2275 ◽  
Author(s):  
K Tateda ◽  
Y Ishii ◽  
T Matsumoto ◽  
N Furuya ◽  
M Nagashima ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Bactericidal Activity ◽  
Direct Evidence ◽  
Dependent Manner ◽  
Intracellular Accumulation ◽  
Prolonged Incubation ◽  
Incubation Periods ◽  
Inhibition Of Protein Synthesis ◽  
Term Administration

Several previous investigators have reported that long-term administration of certain macrolides is efficacious in patients with persistent pulmonary Pseudomonas aeruginosa infections, even though the clinically achievable concentrations of these medications are far below their MICs. In the present study, we examined how sub-MICs of macrolide antibiotics affect the viability of and protein synthesis in several strains of P. aeruginosa. We report that 48 h, but not 12 or 24 h, of growth on agar containing a clinically achievable concentration of azithromycin (0.5 microgram/ml, 1/128 the MIC) significantly reduces the viability of strain PAO-1. Similar effects were seen with erythromycin and clarithromycin at 2 micrograms/ml (1/128 and 1/64 the respective MICs), whereas josamycin, oleandomycin, ceftazidime, tobramycin, minocycline, and ofloxacin had no effect on viability, even following 48 h of incubation with concentrations representing relatively high fractions of their MICs. The bactericidal activity of azithromycin seen following 48 h of incubation was not limited to strain PAO-1 but was also seen against 13 of 14 clinical isolates, including both mucoid and nonmucoid strains. Although viability was not decreased prior to 48 h, we found that 4 micrograms of azithromycin per ml inhibits protein synthesis after as little as 12 h and that protein synthesis continues to decrease in a time-dependent manner. We likewise found that P. aeruginosa accumulates azithromycin intracellulary over the period from 12 to 36 h. These results suggested that sub-MICs of certain macrolides are bactericidal to P. aeruginosa when the bacteria are exposed to these antibiotics for longer periods. Exposure-dependent intracellular accumulation of the antibiotic and inhibition of protein synthesis may partially account for the antipseudomonal activity of macrolides over relatively prolonged incubation periods.

scholarly journals Rapid, Labile, and Protein Synthesis– Independent Short-Term Memory in Conditioned Taste Aversion

1999 ◽  
Vol 6 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Thomas A. Houpt ◽  
RoseAnn Berlin
Keyword(s):  
Protein Synthesis ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Short Term Memory ◽  
Long Term Memory ◽  
Low Doses ◽  
Central Administration ◽  
Short Term ◽  
Term Memory

Short-term memory is a rapid, labile, and protein-synthesis-independent phase of memory. The existence of short-term memory in conditioned taste aversion (CTA) learning has not been demonstrated formally. To determine the earliest time at which a CTA is expressed, we measured intraoral intake of sucrose at 15 min, 1 hr, 6 hr, or 48 h after contingent pairing of an intraoral infusion of 5% sucrose (6.6 ml over 6 min) and toxic lithium chloride injection (76 mg/kg). Rats were implanted with intraoral catheters to allow presentation of taste solutions at arbitrary times. Intraoral intake was measured under conditions of long-delay, single-trial learning typical of CTA. Rats decreased intraoral intake of sucrose at 15 min after contingent pairing of sucrose and LiCl, but not after noncontingent LiCl or sucrose. Thus CTA learning can be expressed rapidly. To determine if short-term CTA memory is labile and decays in the absence of long-term memory, we measured intraoral intake of sucrose after pairing sucrose with low doses of LiCl. Rats received an intraoral infusion of 5% sucrose (6 ml/6 min); 30 min later LiCl was injected at three different doses (19, 38, or 76 mg/kg). A second intraoral infusion of sucrose was administered 15 min, 1 hr, 3 hr, 4.5 hr, 6 hr, or 48 hr later. The formation of long-term CTA memory was dependent on the dose of LiCl paired with sucrose during acquisition. Low doses of LiCl induced a CTA that decayed within 6 hr after pairing. Central administration of the protein synthesis inhibitor cycloheximide prior to LiCl injection blocked long-term CTA expression at 6 and 48 hr, but not short-term CTA expression at 1 hr. Thus, short-term memory for CTA learning exists that is acquired rapidly and independent of protein synthesis, but labile in the absence of long-term memory formation.

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