Changes In Rate Of Protein Synthesis Research Articles

Effective extraction of polyribosomes exposes gene expression strategies in primary astrocytes.

Regulation of mRNA translation in astrocytes gains a growing interest. However, until now, successful ribosome profiling of primary astrocytes has not been reported. Here, we optimized the standard 'polysome profiling' method and generated an effective protocol for polyribosome extraction, which enabled genome-wide assessment of mRNA translation dynamics along the process of astrocyte activation. Transcriptome (RNAseq) and translatome (Riboseq) data generated at 0, 24and 48 hafter cytokines treatment, revealed dynamic genome-wide changes in the expression level of ∼12000 genes. The data clarify whether a change in protein synthesis rateresults from a change in mRNA levelor translation efficiency per se. It exhibitdifferent expression strategies, based on changes in mRNA abundance and/or translation efficiency, which arespecifically assigned to gene subsets depending on their function. Moreover, the study raises an important take-home message related to the possible presence of 'difficult to extract' polyribosome sub-groups, in all cell types, thus illuminating the impact of ribosomes extraction methodology on experiments addressing translation regulation.

Biochemical bases of growth variation during development: A study of protein turnover in pedigreed families of bivalve larvae (Crassostrea gigas)

Animal size is a highly variable trait regulated by complex interactions between biological and environmental processes. Despite the importance of understanding the mechanistic bases of growth, predicting size variation in early stages of development remains challenging. Pedigreed lines of the Pacific oyster (Crassostrea gigas) were crossed to produce contrasting growth phenotypes to analyze the metabolic bases of growth variation in larval stages. Under controlled environmental conditions, substantial growth variation of up to 430% in shell length occurred among 12 larval families. Protein was the major biochemical constituent in larvae, with an average protein-to-lipid content ratio of 2.8. On average, 86% of protein synthesized was turned over (i.e. only 14% retained as protein accreted), with a regulatory shift in depositional efficiency resulting in increased protein accretion during later larval growth. Variation in protein depositional efficiency among families did not explain the range in larval growth rates. Instead, changes in protein synthesis rates predicted 72% of growth variation. High rates of protein synthesis to support faster growth, in turn, necessitated greater allocation of the total ATP pool to protein synthesis. An ATP allocation model is presented for larvae of C. gigas that includes the major components (82%) of energy demand: protein synthesis (45%), ion pump activity (20%), shell formation (14%) and protein degradation (3%). The metabolic trade-offs between faster growth and the need for higher ATP allocation to protein synthesis could be a major determinant of fitness for larvae of different genotypes responding to the stress of environmental change.

Photo and Nutritional Regulation of Euglena Organelle Development.

Euglena can use light and CO2, photosynthesis, as well as a large variety of organic molecules as the sole source of carbon and energy for growth. Light induces the enzymes, in this case an entire organelle, the chloroplast, that is required to use CO2 as the sole source of carbon and energy for growth. Ethanol, but not malate, inhibits the photoinduction of chloroplast enzymes and induces the synthesis of the glyoxylate cycle enzymes that comprise the unique metabolic pathway leading to two carbon, ethanol and acetate, assimilation. In resting, carbon starved cells, light mobilizes the degradation of the storage carbohydrate paramylum and transiently induces the mitochondrial proteins required for the aerobic metabolism of paramylum to provide the carbon and energy required for chloroplast development. Other mitochondrial proteins are degraded upon light exposure providing the amino acids required for the synthesis of light induced proteins. Changes in protein levels are due to increased and decreased rates of synthesis rather than changes in degradation rates. Changes in protein synthesis rates occur in the absence of a concomitant increase in the levels of mRNAs encoding these proteins indicative of photo and metabolic control at the translational rather than the transcriptional level. The fraction of mRNA encoding a light induced protein such as the light harvesting chlorophyll a/b binding protein of photosystem II, (LHCPII) associated with polysomes in the dark is similar to the fraction associated with polysomes in the light indicative of photoregulation at the level of translational elongation. Ethanol, a carbon source whose assimilation requires carbon source specific enzymes, the glyoxylate cycle enzymes, represses the synthesis of chloroplast enzymes uniquely required to use light and CO2 as the sole source of carbon and energy for growth. The catabolite sensitivity of chloroplast development provides a mechanism to prioritize carbon source utilization. Euglena uses all of its resources to develop the metabolic capacity to utilize carbon sources such as ethanol which are rarely in the environment and delays until the rare carbon source is no longer available forming the chloroplast which is required to utilize the ubiquitous carbon source, light and CO2.

Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity

Ageing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated. 8 obese men with T2DM, and 12 age-matched controls were studied (age 68±3 vs. 68±6y; BMI: 30±2 vs. 27±5kgm-2). Body composition was measured by dual-X-ray absorptiometry. Insulin and glucose were clamped at post-absorptive concentrations (13±2 vs. 9±3mUl-1; 7.4±1.9 vs. 4.6±0.4mmoll-1; T2DM vs. controls). Fractional synthetic rates (FSR) of myofibrillar and sarcoplasmic proteins were measured as the rate of incorporation of [13C] leucine during a primed, constant infusion of [1-13C] α-ketoisocaproic acid, 3h after 10 or 20g of essential amino acids (EAA) were orally administered. Protein expression of total and phosphorylated mTOR signalling proteins was determined by Western blot analysis. Despite a significantly lower appendicular lean mass index and a greater fat mass index in T2DM vs. controls, basal myofibrillar and sarcoplasmic and post-prandial myofibrillar FSR were similar. After 20g EAA, stimulation of sarcoplasmic FSR was slightly blunted in T2DM patients. Furthermore, feeding 20g EAA increased phosphorylation of mTOR, p70S6k and 4E-BP1 by 60-100% in controls with no response observed in T2DM. There was clear dissociation between changes in mTOR signalling versus changes in protein synthesis rates. However, the intact anabolic response of myofibrillar FSR to feeding in both groups suggests anabolic resistance may not explain accelerated muscle loss in T2DM.

Purine biosynthesis is the bottleneck in trimethoprim-treated Bacillus subtilis.

Trimethoprim is a folate biosynthesis inhibitor. Tetrahydrofolates are essential for the transfer of C1 units in several biochemical pathways including purine, thymine, methionine, and glycine biosynthesis. This study addressed the effects of folate biosynthesis inhibition on bacterial physiology. Two complementary proteomic approaches were employed to analyze the response of Bacillus subtilis to trimethoprim. Acute changes in protein synthesis rates were monitored by radioactive pulse labeling of newly synthesized proteins and subsequent 2DE analysis. Changes in protein levels were detected using gel-free quantitative MS. Proteins involved in purine and histidine biosynthesis, the σB -dependent general stress response, and sporulation were upregulated. Most prominently, the PurR-regulon required for de novo purine biosynthesis was derepressed indicating purine depletion. The general stress response was activated energy dependently and in a subpopulation of treated cultures an early onset of sporulation was observed, most likely triggered by low guanosine triphosphate levels. Supplementation of adenosine triphosphate, adenosine, and guanosine to the medium substantially decreased antibacterial activity, showing that purine depletion becomes the bottleneck in trimethoprim-treated B. subtilis. The frequently prescribed antibiotic trimethoprim causes purine depletion in B. subtilis, which can be complemented by supplementing purines to the medium.

Tyrosine positron emission tomography and protein synthesis rate in pituitary adenoma: Different effects of surgery and radiation therapy

IntroductionPositron emission tomography (PET) using amino acid tracers is able to establish biochemical tumour characterization in vivo. The use of PET in the follow-up of non-functioning pituitary adenomas (NFA) and growth hormone producing pituitary adenomas (GHA) after surgery and radiation treatment is not yet clear. MethodsTo determine the value of PET before and after transsphenoidal neurosurgery in NFA and GHA, we investigated 12 patients with pituitary adenoma (9 NFA and 3 GHA) before and 4months after surgery with magnetic resonance imaging (MRI) and tyrosine PET (TYR-PET). Three years after radiation therapy TYR-PET was used to document residual activity in 6 of these patients (4 NFA- and 2 GHA). Tumour size was quantified by computerized MRI measurements. In TYR-PET, tumour activity was assessed by computerized measurements of the hot spot and by determination of protein synthesis rate (PSR). ResultsIn response to surgery, MRI showed a median tumour volume reduction of 58% (P<0.01). TYR-PET demonstrated 62% volume reduction (P<0.02), but no change in PSR (P>0.30). After radiation therapy the MRI-volumes of the residual pituitary adenomas did not change but the volume of the hot spot on TYR-PET-imaging was reduced by 58% (P=0.02), and PSR decreased in 5 of 6 patients (P=0.12). ConclusionAmino acid PET tumour activity is reduced parallel with MRI volume changes after surgery. The decrease in TYR-PET activity after radiation therapy, despite unaltered MRI tumour volume, supports the concept that it is possible to follow biological tumour activity with this technique. The diagnostic merit of this tracer technique, predicting pituitary adenoma re-growth, needs to be validated in a large prospective study.

Differential Regulation of Protein Synthesis and mTOR Signaling in Skeletal Muscle and Visceral Tissues of Neonatal Pigs after a Meal

Neonates have a high rate of growth driven by elevated rates of skeletal muscle protein synthesis. Feeding stimulates protein synthesis but the time course of the changes in different tissues has not been determined. The aim of this study was to evaluate the time course of the changes in protein synthesis rates and translation initiation factor activation in skeletal muscle and visceral tissues after a meal. Neonatal pigs (n=36; 5–7 day old) received a meal providing one‐sixth of daily requirements and were sacrificed at 0, 30, 60, 90, 120, or 240 min after feeding. Protein synthesis increased 30 to 120 min in glycolytic muscles, 30 to 90 min in mixed fiber type muscle and did not increase in oxidative muscle post‐feeding. Protein synthesis increased in liver 30 to 120 min, jejunum 30 to 60 min and pancreas 30 min post‐feeding and did not increase in kidney and heart. Eukaryotic initiation factor (eIF) 4E binding protein (4EBP1) and rp S6 kinase 1 (S6K1) phosphorylation increased 30 to 90 min in all tissues. These results suggest that feeding stimulates mTOR signaling in skeletal muscle and visceral tissues. However, mTOR activation alone was not sufficient to stimulate protein synthesis in all tissues. (Supported by NIH grants AR‐44474 and AR‐51563 and USDA/ARS 6250510000‐33).Grant Funding Source: NIH grants AR‐44474 and AR‐51563 and USDA/ARS 6250510000‐33

New convenient defined media for [35S]methionine labelling and proteomic analyses of probiotic lactobacilli

To develop experimental conditions for efficient protein radiolabelling and two-dimensional (2D) polyacrylamide gel electrophoresis for investigation of stress proteomes of probiotic Lactobacillus spp. Three chemically defined media (CDM) optimized from a commercial medium supported rapid growth of the probiotic Lactobacillus rhamnosus E97800, Lactobacillus brevis ATCC 8287 and Lactobacillus reuteri E97849, and a broad range of other lactic acid bacteria. These CDM allowed efficient protein radiolabelling, requiring as little as 200 mul of logarithmic culture and pulse-chase labelling of 20 min to detect c. 300 distinct protein spots in a mini-scale 2D-gel. Proteins including DnaK, GroEL and ClpATPases were identified from the 2D-gels by immunoblotting. Radiolabelling coupled with 2D gel electrophoresis provides a sensitive means to monitor changes in protein synthesis rates in probistic lactobacilli. Efficient tools for proteomic analyses of probiotic Lactobacillus were developed and applied for stress-response studies.

Regulation of the Cln3-Cdc28 kinase by cAMP in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae grows at widely varying rates in different growth media. In order to maintain a relatively constant cell size, yeast cells must regulate the rate of progress through the cell cycle to match changes in growth rate, moving quickly through G1 in rich medium, and slowly in poor medium. We have examined connections between nutrients, and the expression and activity of Cln3-Cdc28 kinase that regulates the G1-S boundary of the cell cycle in yeast, a point referred to as Start. We find that Cln3 protein levels are highest in glucose and lower in poorer carbon sources. This regulation involves both transcriptional and post-transcriptional control. Although the Ras-cAMP pathway does not appear to affect CLN3 transcription, cAMP increases Cln3 protein levels and Cln3-Cdc28 kinase activity. This regulation requires untranslated regions of the CLN3 message, and can be explained by changes in protein synthesis rates caused by cAMP. A model for CLN3 regulation and function is presented in which CLN3 regulates G1 length in response to nutrients.

11C-tyrosine position emission tomography and 1H magnetic resonance spectroscopy of the response of brain gliomas to radiotherapy.

We monitored 10 patients with unresected (9) or partially resected (1) supratentorial gliomas with 11C-tyrosine position emission tomography (TYR-PET) before and after radiotherapy. TYR-PET tumour volumes were measured using a threshold technique. In seven patients the tumour volume decreased after radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients the tumour protein synthesis rate (PSR) was calculated using a dynamic study protocol in combination with a PATLAK analysis. There were no changes in PSR after radiotherapy, but the PSR was calculated on the remaining tumour volume using the same threshold technique as before therapy, i.e. the decrease in tumour volume was not taken into account. In eight patients the PET data were compared with magnetic resonance spectroscopic imaging (1H-MRSI) performed simultaneously. Although there was no statistically significant correlation between TYR-PET volume changes and 1H-MRSI choline level we observed a simultaneous decrease in volume and choline in four patients.

Tissue-specific changes in protein synthesis rates in vivo during anoxia in crucian carp.

Mechanisms of anoxia tolerance were investigated in crucian carp. Rates of protein synthesis were calculated in selected tissues of normoxic and anoxic animals. Exposure to 48 h of anoxia resulted in a significant reduction in protein synthesis in the liver (> 95%), heart (53%), and red and white muscle (52 and 56%, respectively), whereas brain protein synthesis rates were unaffected. Seven days of anoxia produced similar results. After 24 h of recovery from a 48-h anoxic period, protein synthesis rates had virtually returned to normoxic values. The effect of anoxia on the amount of RNA (relative to protein) varied depending on the tissue and also the length of exposure (except in the brain, where it was consistently reduced). However, the effect on RNA translational efficiency was purely tissue specific (i.e., independent of exposure time) and was unaffected in the heart, reduced in the liver and red and white muscle, and increased in the brain. Downregulation of protein synthesis on a tissue-specific basis appears to be a significant mechanism for energy conservation as well as maintaining neural function, thus promoting survival during anoxia.

Carboxy-terminal Residues of Mouse Thymidine Kinase are Essential for Rapid Degradation in Quiescent Cells

The expression of murine thymidine kinase (TK) is highly dependent on the growth state of the cell. The enzyme is nearly undetectable in resting (G 0) cells, but TK protein levels rise dramatically when serum-stimulated cells reach the G1/S boundary. To study post-transcriptional regulation of TK expression, Ltk −cells were stably transfected with the coding region of the TK cDNA under the control of a constitutive SV40 promoter. While TK mRNA levels were growth independent in this cell line, TK protein expression and enzyme activity were low in resting cells but increased strongly after growth stimulation by serum. Measurements of translation efficiency and protein stability by immunoprecipitation and pulse-chase experiments indicated that a fourfold change in protein synthesis rate and a sevenfold rise in protein stability are responsible for the increase of TK expression. Progressive deletion of three, six, ten and 20 carboxy-terminal residues of the enzyme resulted in a stepwise loss of its growth-dependent regulation. In addition, a truncated protein lacking the last 30 amino acid residues was expressed at a level tenfold higher than the full-length polypeptide. Further analysis showed that removal of the C-terminal 30 residues did not affect the translation rate, but resulted in the drastic increase in protein half-life. These results demonstrate that residues at the carboxy terminus of the murine enzyme are essential for the growth- dependent regulation of TK protein stability.

Protein synthesis in the hypertrophied heart of spontaneously hypertensive rats and a comparison of the effects of an ACE‐inhibitor and a calcium channel antagonist

The aim of the investigation was to assess and compare the effects of a calcium channel antagonist, (i.e. amlodipine) and an ACE-inhibitor (i.e. lisinopril) in reducing chronic left ventricular hypertrophy in 15-week old spontaneously hypertensive rats (SHR). Changes in cardiac hypertrophy were assessed after 8 weeks by measuring the fractional rates of protein synthesis using a 'flooding dose' of [3H]-phenylalanine for 10 min. Blood pressure was monitored throughout the treatment period in both SHR and Wistar-Kyoto control rats (WKY). The results showed a decrease in blood pressure by amlodipine after 1 week of treatment which was further reduced at 4 to 8 weeks. Lisinopril caused immediate and sustained reductions in blood pressure (190 mmHg to 130 mmHg, P < 0.001). After 8 weeks of treatment in SHR rats, amlodipine had no significant effect on left ventricular weight (P > 0.05), whereas lisinopril caused a marked reduction. The protein content and RNA were also not changed by amlodipine. In contrast, lisinopril significantly lowered the tissue protein, RNA and DNA content (P < 0.001). The changes in the left ventricles of lisinopril-treated SHR rats were accompanied by an increase in the fractional synthesis rate of left ventricular myofibrillar proteins (+12 per cent, P < 0.025). The synthesis rate per unit RNA was also increased in right ventricular tissue of lisinopril-treated SHR rats. However, amlodipine had no effect on the fractional synthesis rates of any of the left-ventricular fractions of SHR rats (P > 0.05). The cellular efficiency in the right ventricle was also increased in amlodipine-treated SHR rats, indicating a moderate effect on protein metabolism. In conclusion, amlodipine had minimal effects in the reduction of established left ventricular hypertrophy (LVH), despite reducing the blood pressure, whereas lisinopril caused regression of LVH. These events were associated with small changes in protein synthesis rates, with the contractile protein showing an increase.

Cell-free translation systems prepared from starfish oocytes faithfully reflect in vivo activity; mRNA and initiation factors stimulate supernatants from immature oocytes.

Meiotic maturation stimulates a change in the translation of stored mRNAs: mRNAs encoding proteins needed for growth of oocytes are translated before meiotic maturation, whereas those encoding proteins required for cleavage are translated after meiotic maturation. Studies of translational regulation during meiotic maturation have been limited by the lack of translationally active cell-free supernatants. Starfish oocytes are ideal for preparing cell-free translation systems because experimental application of the hormone 1-methyladenine induces their maturation, synchronizing meiosis. We have prepared such systems from both immature and mature oocytes of starfish. Changes in protein synthesis rates and the specificity of proteins synthesized in these cell-free translation supernatants mimic those seen in vivo. Supernatants both from immature and mature oocytes have a high capacity to initiate new translation because 90% of the proteins made are newly initiated from mRNAs. Cell-free supernatants from mature oocytes have a much higher rate of initiation of translation than those from immature oocytes and use the 43S preinitiation complexes more efficiently in initiation of translation. Similarly, we have shown that mRNAs and initiation factors are rate limiting in cell-free translation systems prepared from immature oocytes. In addition, cell-free translation systems prepared from immature oocytes are only slightly, if at all, inhibitory to cell-free translation systems from mature oocytes. Thus, soluble inhibitors, if they exist, are rapidly converted by cell-free supernatants from mature oocytes. The similarities between translation in our starfish cell-free translation systems and in intact oocytes suggests that the cell-free translation systems will be useful tools for further studies of maturation events and translational control during meiosis.

Timing of Changes in Protein Synthesis Pattern in Elicitor-Treated Cell Suspension Cultures of Parsley ( Petroselinum crispum)

Abstract The timing of changes in the protein synthesis pattern of elicitor-treated, [35S]methionine-labelled parsley cells (Petroselinum crispum) was analyzed by two-dimensional gel electropho­ resis. Five groups were distinguished from a large number of elicitor-responsive as well as un­ responsive proteins. Two groups were synthesized de novo either early or late after elicitor ap­ plication; two other groups were strongly reduced in their rates of synthesis either early or late after elicitor application; and one group was not appreciably affected at all. The elicitor-in-duced changes altered the total protein com position considerably. A few selected, induced pro­ teins were functionally identified. These included two early induced enzymes, phenylalanine amm onia-lyase (PAL) and 4-coum arate:C oA ligase (4C L), and a late induced enzyme, a ber-gaptol O-methyltransferase (BM T) which is specifically involved in the biosynthesis of furano-coumarin phytoalexins. The biological significance of the observed differential timing of changes in protein synthesis rates is discussed.

Influence of feeding on protein metabolism in Atlantic salmon ( Salmo salar)

Two experiments were conducted to study the post-prandial changes in protein synthesis rate of different tissues in juvenile Atlantic salmon after an i.v. injection of a large dose (1.5 μmole/g) of L-[2,3- 3H]-leucine. In the first experiment, the changes in protein synthesis rate of the muscle and scales were followed over a period of 18 h after a meal, in salmon (mean body weight 43.4 g) starved for 1 week. The rate of protein synthesis in muscle increased until 18 h after feeding. No significant changes were observed in the protein synthesis rate of the scales. In the second experiment, the salmon (mean body weight 36.8 g) were regularly fed on a commercial diet. Immediate analysis of protein metabolism (2 h after the morning meal) as compared with analysis after an overnight fast showed no significant effect of feeding on the protein synthesis rate in liver, gill, digestive tract and muscle.

Respiration of soybean plants in relation to their physiological conditions. IV. Time course changes in nitrogen metabolism in a leaf.

Time course changes in nitrogen transformation among nitrogenous compounds in a detached leaf of soybean was examined in relation to respiration rate. Nitrogen content in protein continued to increase for 12 hours from the onset of dark period. This apparent protein synthesis showed a high peak betwreen 0:00 and 3:00 in an expanding leaf, and a low peak in an expanded leaf, followed by a steep decrease in both leaves. This trend of protein synthesis fitted to the time course change of respiration rate. The time of maximum protein synthesis rate corresponded to that of midnight rise of respiration appearance. It was, therefore, supposed that the time course changes in respiration which has been examined in the previous papers, is the reflection of diurnal changes in protein synthesis rate in a leaf.

The effect of sepsis in rats on skeletal muscle protein synthesis in vivo and in periphery and central core of incubated muscle preparations in vitro

Recent studies demonstrated the development of a central, hypoxic core in incubated rat skeletal muscles. The influence of a central core on changes in protein synthesis rate, observed in incubated muscles from septic rats, is not known. In the present study, intact soleus muscles from 40 to 60-g sham-operated control rats and from septic rats (16 hours after cecal ligation and puncture) were incubated in vitro in a flaccid or stretched state. Protein synthesis rate was determined in whole muscle and in the central core and periphery of the muscle by measuring incorporation of 14C-phenylalanine into protein. Protein synthesis rate in vivo was measured with a flooding-dose technique using 3H-phenylalanine. The development of a central, hypoxic core in incubated muscles was assessed histochemically by staining the muscles for α-glucan phosphorylase activity. A central core with loss of α-glucan phosphorylase activity was noted after incubation for 30 minutes in both control and septic muscles. The protein synthesis rate was lower in the central core than in the periphery of incubated flaccid control muscles. In all other in vitro muscle preparations, however, there were no significant differences in protein synthesis rate among whole muscles, central core, and periphery. Protein synthesis rate in septic muscles was reduced to a similar extent, approximately 20%, in vivo and in the different in vitro preparations, both when measured in whole muscle and in the central core or periphery. The present results suggest that incubated soleus muscles from small rats can be used to evaluate the effect of sepsis on protein synthesis, despite the development of a central, hypoxic core in these muscle preparations.

Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells.

Nerve growth factor induces neurite process formation in pheochromacytoma (PC12) cells and causes the parallel increase in levels of the microtubule-associated proteins, tau and MAP1, as well as increases in tubulin levels. Mechanisms to insure balanced accumulation of microtubule proteins and make their levels highly responsive to nerve growth factor were investigated. The effects on tau, MAP1, and tubulin are due to changes in protein synthesis rates, which for tau and tubulin we could show are due in part to changes in the mRNA levels. Whereas tubulin shows feedback regulation to modulate synthesis up or down, tau protein synthesis is not affected in a straightforward way by microtubule polymerization and depolymerization. The degradation of tau, MAP1, and both tubulin polypeptides, however, are stimulated by microtubule depolymerization caused by colchicine, or nerve growth factor removal. Combined feedback on synthesis and stability make tubulin levels highly responsive to assembly states. In addition, the linkage of tau and MAP1 turnover with the state of microtubule polymerization amplifies any change in their rate of synthesis, since tau and MAP1 promote microtubule polymerization. This linkage lends itself to rapid changes in the state of the system in response to nerve growth factor.

Association of cholecystectomy with pancreatic growth and increased plasma levels of cholecystokinin in the syrian golden hamster

This study examined the effect of cholecystectomy on plasma concentrations of cholecystokinin (CCK) and pancreatic growth. Seventy female Syrian golden hamsters were used in the investigation. Half the animals underwent cholecystectomy and half had a sham procedure. Following cholecystectomy, significant increases were observed in pancreatic weight (11–41%), total DNA content (8–16%), total protein content (9–19%), DNA synthesis rate (57–200%), and in random plasma CCK concentrations (12–81%) in comparison to the control group. There was no significant change in protein synthesis rate. We conclude that cholecystectomy may have a significant trophic effect on the pancreas and that this effect may be mediated by an increase in circulating levels of CCK.