Influx and incorporation into protein of l-phenylalanine in the perfused rat pancreas: effects of amino acid deprivation and carbachol

Sweiry, Jh; Pw, Emery; Muñoz, Manuel J.; Doolabh, K.; Ge, Mann

doi:10.1016/0005-2736(91)90155-2

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…The partial reduction of total protein synthesis seen in the present study with mice indicates that in the basal or interdigestive state, pancreatic protein synthesis (and consequently, digestive enzyme synthesis) is reduced but not completely blocked; it remains active to maintain certain levels of stored digestive enzymes and replace the ones that are still being secreted (41). Not surprisingly, the fractional rates of pancreatic protein synthesis are among the highest in mammalian tissues (45). Moreover, the lack of effect of fasting on Akt activity (Fig.…”

Section: Discussionmentioning

confidence: 50%

“…First, the specific activity of the intracellular unincorporated pancreatic compartment was measured at different time points to confirm that it remained almost constant for a certain period of time after injection (Fig. 1A) (12,24,45). Second, the actual incorporation of L-[ 3 H]Phe into pancreatic protein at different time points was calculated (Fig.…”

Section: Discussionmentioning

confidence: 95%

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Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA

Sans

Lee

DʼAlecy

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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To determine the mechanism of meal-regulated synthesis of pancreatic digestive enzymes, we studied the effect of fasting and refeeding on pancreatic protein synthesis, relative mRNA levels of digestive enzymes, and activation of the translational machinery. With the use of the flooding dose technique with L-[3H]phenylalanine, morning protein synthesis in the pancreas of Institute for Cancer Research mice fed ad libitum was 7.9 +/- 0.3 nmol phenylalanine.10 min(-1).mg protein(-1). Prior fasting for 18 h reduced total protein synthesis to 70 +/- 1.4% of this value. Refeeding for 2 h, during which the mice consumed 29% of their daily food intake, increased protein synthesis to 117.3 +/- 4.9% of the control level. Pancreatic mRNA levels of amylase, lipases, trypsins, chymotrypsin, elastases, as well as those for several housekeeping genes tested were not significantly changed after refeeding compared with fasted mice. By contrast, the major translational control pathway involving Akt, mTOR, and S6K was strongly regulated by fasting and refeeding. Fasting for 18 h decreased phosphorylation of ribosomal protein S6 to almost undetectable levels, and refeeding highly increased it. The most highly phosphorylated form of the eIF4E binding protein (4E-BP1) made up the 14.6% of total 4E-BP1 in normally fed animals, was only 2.8% after fasting, and was increased to 21.4% after refeeding. This was correlated with an increase in the formation of the eIF4E-eIF4G complex after refeeding. By contrast, feeding did not affect eIF2B activity. Thus food intake stimulates pancreatic protein synthesis and translational effectors without increasing digestive enzyme mRNA levels.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 95%

Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA

Sans

Lee

DʼAlecy

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Thus the observed inhibition of pancreatic protein synthesis is not likely related to a decrease in the pancreas precursor pool uptake. Finally, the flooding dose technique is advantageous in the present study not only because it is reliable, but also because it can be used in unrestrained and unanesthetized animals (13) and has been well validated in muscle (10,16), liver (33), and pancreas (61).…”

Section: Discussionmentioning

confidence: 99%

Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F

Sans

DiMagno

DʼAlecy

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F. Am J Physiol Gastrointest Liver Physiol 285: G517-G528, 2003. First published May 28, 2003 10.1152/ajpgi.00540.2002.-Acute pancreatitis (AP) has been shown in some studies to inhibit total protein synthesis in the pancreas, whereas in other studies, protein synthesis was not affected. Previous in vitro work has shown that high concentrations of cholecystokinin both inhibit protein synthesis and inhibit the activity of the guanine nucleotide exchange factor eukaryotic initiation factor (eIF)2B by increasing the phosphorylation of eIF2␣. We therefore evaluated in C57BL /6 mice the effects of caerulein-induced AP on pancreatic protein synthesis, eIF2B activity and other protein translation regulatory mechanisms. Repetitive hourly injections of caerulein were administered at 50 g/kg ip. Pancreatic protein synthesis was reduced 10 min after the initial caerulein administration and was further inhibited after three and five hourly injections. Caerulein inhibited the two major regulatory points of translation initiation: the activity of the guanine nucleotide exchange factor eIF2B (with an increase of eIF2␣ phosphorylation) and the formation of the eIF4F complex due, in part, to degradation of eIF4G. This inhibition was not accounted for by changes in the upstream stimulatory pathway, because caerulein activated Akt as well as phosphorylating the downstream effectors of mTOR, 4E-BP1, and ribosomal protein S6. Caerulein also decreased the phosphorylation of the eukaryotic elongation factor 2, implying that this translation factor was not inhibited in AP. Thus the inhibition of pancreatic protein synthesis in this model of AP most likely results from the inhibition of translation initiation as a result of increased eIF2␣ phosphorylation, reduction of eIF2B activity, and the inhibition of eIF4F complex formation. protein translation; mice IT HAS BEEN WELL ESTABLISHED that experimental acute pancreatitis (AP) inhibits pancreatic exocrine secretion (32,36,55,60). It has also been reported that pancreatic protein synthesis is unaffected by AP, leading to accumulation of digestive enzymes (5,30,55,60). However, other studies have shown inhibition of pancreatic protein synthesis in both in vivo experimental AP studies (17,26,32,36,46) and in vitro models of AP using CCK hyperstimulation of isolated acini (31,48,56). This study seeks to clarify how protein synthesis is affected in an in vivo caerulein hyperstimulation model of AP in mice, using the "flooding dose" technique to measure protein synthesis and by analyzing the state of key regulatory mechanisms in protein translation.Protein synthesis or translation of mRNA into protein has several known major regulatory steps involving initiation and elongation phases. The first major step in translation initiation is the binding of the initiator tRNA iMet to the 40 S ribosomal subunit, which is regulated by the eukaryotic initiation factor (eIF)2 (27, 51). In order for eIF2 to p...

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“…Alternatively, stable isotopes can be used with derivatization and quantitation by gas chromatography-mass spectrometry (GC-MS). Finally, the flooding dose technique is advantageous not only because it is reliable, but also because it can be used in unrestrained and unanesthetized animals (2) and has been well validated in muscle (20), liver (14), and pancreas (29).…”

Section: Measurement Of Pancreatic Protein Synthesis In Vivo the Flomentioning

confidence: 99%

“…The flooding dose technique, was originally described by Garlick and co-workers for heart (3) and later validated by Sweiry and co-workers (29) in rat pancreas. We have adapted the protocol of Lundholm and co-workers (14) described to measure liver protein synthesis to total pancreas protein synthesis in mice (23,25) and rats (26), and measured the uptake of radioactive phenylalanine into pancreas as a function of time.…”

Section: Measurement Of Pancreatic Protein Synthesis In Vivo the Flomentioning

confidence: 99%

Measurement of pancreatic protein synthesis

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The Pancreapedia: Exocrine Pancreas Knowledge Base

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Influx and incorporation into protein of l-phenylalanine in the perfused rat pancreas: effects of amino acid deprivation and carbachol

Cited by 6 publications

References 26 publications

Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA

Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA

Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F

Measurement of pancreatic protein synthesis

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