Thyroid hormones regulate adrenal chromaffin cell SNAP-25.
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Animals↗
Biomedical subjects
R Hepp
Publications and source records attributed to R Hepp.
Adrenal gland SNAP-25 expression is altered in thyroid hormone receptor knock-out mice.
SNAP-25 is a protein in neurons and neuroendocrine cells, which is involved, together with syntaxin and VAMP, in neurotransmitter release and neurite outgrowth. Since the thyroid hormone receptors TR alpha and TR beta are essential for nervous system development, their possible role in regulating the expression of these vesicle trafficking proteins was examined by analysing SNAP-25 levels in TR alpha and TR beta knock-out mice. Immunoblotting and RT-PCR showed that SNAP-25 levels are increased in the adrenal gland, but not in cerebellum, in knock-out mice, while syntaxin-1 and VAMP-2 are unaffected in either tissue. Treatment of the pheochromocytoma-derived cell line PC12 with the thyroid hormone L-3,5,3'-triiodothyronine (T3) decreased SNAP-25 expression. Together, these data suggest that thyroid hormones exert a negative regulatory effect on SNAP-25 in adrenal medullary neuroendocrine cells.
Adrenal Medulla↗
NGF enhances depolarization effects on SNAP-25 expression: induction of SNAP-25b isoform.
The 25 kDa synaptosomal associated protein (SNAP-25), which is implicated in neuronal plasticity and neurosecretion, exists as two isoforms generated by alternative splicing of exons 5a and 5b. The aim of the present study was to characterize factors influencing isoform expression. We report that chronic depolarization of PC12 cells alone or in the presence of NGF induces the expression of isoform-b, in addition to a 1.8- to 3-fold increase in SNAP-25 mRNA and protein as determined by immunoblotting and combined RT-PCR and Southern blot analysis. When cerebellar granule neurons were cultured in elevated K+, the predominant isoform switched from SNAP-25a to SNAP-25b. Taken together these results suggested that chronic depolarization regulates the transcription and processing of SNAP-25 mRNA.
Amino Acid Sequence↗
SNAREs during development.
Soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) molecules are implicated in many fundamental cellular processes that require membrane fusion, and the interactions of the SNARE proteins, SNAP-25, syntaxin and VAMP/synaptobrevin, have been extensively studied. This review documents recent data on their role at different stages of development. SNARE proteins are expressed very early and play important roles in fertilization and in cell division during early embryogenesis. In the developing nervous system, they are important for neurite outgrowth and transformation of the growth cone into the mature synapse. In the neuroendocrine system, in addition to neurosecretion, they are involved in processes related to morphological plasticity. Although few data exist on regulation of SNARE proteins during development, growth factors, intracellular messengers and depolarization are known to modify their cellular expression. The putative importance of these factors during development is discussed.
Animals↗
SNAP-25 regulation during adrenal gland development: comparison with differentiation markers and other SNAREs.
Synaptosomal-associated protein of 25 kDa (SNAP-25) is one of a limited number of soluble N-ethylmaleimide-sensitive fusion attachment protein receptors (SNAREs) that play a major role in membrane docking of synaptic vesicles and secretory granules during regulated exocytosis. We have previously shown that SNAP-25 levels differ between noradrenergic and adrenergic chromaffin cell populations of the adult adrenal gland. We examine SNAP-25 expression by immunofluoresence in cells of the sympathoadrenal lineage in the rat during late embryonic and postnatal development. In parallel, tyrosine hydroxylase was used to identify sympathoadrenal cells, phenylethanolamine N-methyltransferase to distinguish adrenergic from noradrenergic chromaffin cells, and chromogranin A to define the presence of secretory granules. In addition, SNAP-25 protein and mRNA levels were followed in adrenal gland extracts by immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Protein levels were compared with those of other molecules also implicated in organelle trafficking, including syntaxin 1 and vesicle-associated membrane protein (VAMP-2) and the nonneuronal analogues SNAP-23 and cellubrevin. This study provides evidence that SNAP-25 is expressed early during development in sympathoadrenal neurons and migrating cells. It is detected in intra-adrenal chromoblasts as soon as they enter the adrenal primordium. Its differential expression between catecholamine chromaffin cell phenotypes is already evident from the 17th embryonic day, future noradrenergic cells appearing to express higher levels than adrenergic cells. The granule maturation marker chromogranin A is expressed in chromaffin cells later than SNAP-25. Both SNAP-25 protein and mRNA increased rapidly in the adrenal gland in the perinatal period to peak during the first postnatal week, after which levels dropped dramatically to adult values. In contrast, levels of both syntaxin and SNAP-23 appeared to remain fairly constant throughout adrenal gland development. VAMP-2 expression increased gradually around birth to reach maximal levels during the first two postnatal weeks, and then decreased slightly. Cellubrevin levels also appeared to increase gradually until adult values were attained by the end of the second postnatal week. The threefold increase of SNAP-25 mRNA shortly after birth compared to the low adult levels suggests that during this period SNAP-25 is implicated in additional functions than regulated secretion, possibly associated with cellular growth or maturation.
Adrenal Glands↗
Cultured glial cells express the SNAP-25 analogue SNAP-23.
Astrocytes release glutamate and aspartate in response to elevated intracellular calcium levels, and it has been proposed that this occurs by a vesicular release mechanism, in which SNARE proteins are implicated. Although syntaxin, synaptobrevin, and cellubrevin have been shown to be expressed by cultured astrocytes, SNAP-25 has not been detected. By using immunocytochemical, immunoblotting, and polymerase chain reaction techniques, the present study demonstrates that SNAP-23, an analogue of SNAP-25, is expressed by astrocytes both in culture and in rat cerebellum. These findings provide additional evidence that astrocytes release excitatory amino acids by a vesicular mechanism involving SNARE proteins. SNAP-23 and also syntaxin 1 and cellubrevin were found to be expressed in glial precursor cells, oligodendrocytes, and microglia. These data suggest that the t-SNAREs SNAP-23 and syntaxin 1 and the v-SNARE cellubrevin participate in general membrane insertion mechanisms involved in diverse glial cell functions such as secretion, phagocytosis, and myelinogenesis.
Animals↗
Differential expression of SNAP-25 isoforms and SNAP-23 in the adrenal gland.
In the rat adrenal gland, we previously observed that SNAP-25 is not restricted to the plasmalemma in noradrenergic cells as it is in adrenergic cells, and hypothesized that SNAP-25 isoform expression is different in the two phenotypes. Expression of SNAP-25 isoforms and SNAP-23 was examined by immunoblotting, immunofluorescence, and RT-PCR. Amplifications of SNAP-25 mRNAs were combined with Southern hybridization, restriction enzyme analysis, and sequencing of cloned PCR products to compare SNAP-25 isoform expression in rat and bovine adrenal glands. SNAP-25 and SNAP-23 mRNA and protein are expressed in the glands; SNAP-23 is enriched in the adrenal cortex, whereas SNAP-25 is restricted to the adrenal medulla. Furthermore, high levels of SNAP-25 and low levels of SNAP-23 are observed in the PC12 cells, whereas both SNAP-25 and SNAP-23 are expressed in adrenal medullary cultures. In all extracts, the SNAP-23 mRNA corresponded to SNAP-23a. SNAP-25a is the major form expressed in rat adrenal glands (75%), as it is in PC12 cells (80%), but both SNAP-25a and SNAP-25b (40% vs. 60%) are expressed in bovine adrenal medulla in situ and in culture. In addition, an enriched population of adrenergic cells (93%) expressed a higher level of SNAP-25b (70%), suggesting that this isoform may not be restricted to fast neurotransmission.
Adrenal Glands↗
[Conservative treatment of ductal carcinoma in situ of the breast].
BACKGROUND: Since the widespread use of mammography, the incidence of ductal carcinoma in situ of the breast has increased. Until few years ago the standard treatment was mastectomy, however, from the analysis of conservative treatment trials for invasive carcinoma, it was evident that ductal carcinoma in situ could also be treated conservatively. This was confirmed later by randomized trials. AIM: To analyze the experience of our Institution with conservative treatment of ductal carcinoma in situ of the breast. PATIENTS AND METHODS: A search through the data base of our Institution found 69 patients treated with lumpectomy and radiotherapy between the years 1976 and 1997. RESULTS: Twenty three of 69 patients (33%) were diagnosed because of a palpable mass. Eleven of twelve were diagnosed prior to 1990 and 12 of 57 after 1990. With a median follow-up of 48 months local control and overall survival is 97%. None of the patients underwent mastectomy. CONCLUSIONS: Conservative treatment of ductal carcinoma in situ of the breast is a reasonable alternative, mainly if we realize that with increasing frequency--the diagnosis is made through mammography and with non-palpable lesions. The results reported in this study are similar to those reported by other centers.
Adult↗
Restriction of indication for automated percutaneous lumbar discectomy based on computed tomographic discography.
This report details the authors' early experience using the automated percutaneous lumbar discectomy (APLD) procedure, developed by Onik et al., in 97 patients with a disc protrusion. In the evaluation of a herniated disc, we used computed tomography (CT) discography. According to the distribution of the dye inside the disc, five different disc types can be differentiated. With a follow-up after 3-7 months, the short-term outcomes of the first 40 APLD-treated patients varied, depending on the shape of the protruded nuclear material. Patients with a broad dye base on CT discography had better short-term outcomes than patients with a narrow dye base. In the next 57 patients we treated with APLD, this tendency was confirmed. The success rate of a consecutive group of patients with a disc protrusion with a broad dye base, treated with APLD, was 80%. In comparison, the patients with a disc protrusion with a narrow dye base had an overall success rate of only 53%. The difference is statistically significant (P < 0.05). The message of this report is that APLD is a useful invasive treatment for patients with a disc protrusion. The outcome depends, however, on the shape of the protruded nuclear material as shown by CT discography, which makes this examination as a conditio sine qua non before treating patients with a disc protrusion with APLD.
Adult↗
An unfused acromial epiphysis. A reason for chronic shoulder pain.
We report on a case of a 34 year-old female patient who had been suffering from chronic shoulder pain for 2 years although she received conservative treatment. The X-ray revealed a prominent distal clavicle and was interpreted as an old AC dislocation. An axillary view showed an os acromiale. The bone scintigraphy confirmed the clinical suspicion of reaction at the epiphysis. Local corticoid injections improved the patient's condition so that she refused further surgical treatment.
Acromion↗
Pharmacokinetic study of methotrexate, folinic acid and their serum metabolites in children treated with high-dose methotrexate and leucovorin rescue.
The pharmacokinetics of methotrexate (MTX), 7-hydroxymethotrexate (7-OHMTX), 2,4-diaminomethylpteroic acid (APA), folinic acid, and 5-methyltetrahydrofolate (5-MTHF) have been studied during 21 high-dose MTX (HDMTX) infusions (5 g.m-2 in 24 h) with leucovorin (LCV) rescue, a component of the therapy of 5 children with acute lymphoblastic leukemia (ALL). The median steady-state concentration of MTX was 66 mumol.l-1. Three elimination half-lifes were determined for MTX: 1.8 h, 6.4 h and a terminal 15 h. The median systemic MTX clearance was 110 mg.m-2.min-1. The 7-OHMTX level increased during each infusion and a Cmax of 19 mumol.l-1 was achieved at the end. Its initial half-life was 5 h and the terminal half-life was 12 h. Thus, the peak serum concentration ratio of 7-OHMTX to MTX was reached 24 h after the end of the infusion at a median ratio of 8. The MTX metabolite APA was detected in concentrations less than 0.06 mumol.l-1. The median folinic acid level during rescue, 48 h after starting the infusion, was 7.0 mumol.l-1 and 18 h following the last dose of LCV it was 0.44 mumol.l-1, leading to ratios of folinic acid to MTX of 31 and 6, respectively. The median 5-MTHF level during rescue was 0.44 mumol.l-1 with a median ratio of 5-MTHF to MTX of 2. Twenty infusions with 48 h MTX levels of less than 0.5 mumol.l-1 were without marked toxicity. Only one patient with a 48 h MTX concentration of 5.5 mumol.l-1 and a ratio of 5-MTHF to MTX of 0.08 suffered from ulcerating mucositis and septicaemia despite increased and prolonged LCV rescue.
Child↗
The influence of tracers on insulin binding to human erythrocytes.
We studied insulin binding to human erythrocytes using two different 125I-insulin-tracers. Erythrocytes of 8 normal subjects were examined using [mono-125II-(Tyr A 14)insulin as tracer. Three of these erythrocyte preparations were examined simultaneously using [125I]insulin, which was randomly iodinated by the chloramine-T-method. Data were analysed by a computerized non-linear least-squares procedure both on the basis of one and two class receptor models. Only the one class receptor model yielded consistent results. When the two class receptor model was applied the low affinity branch of the Scatchard plot was not reproducible. On the basis of the one class receptor model the number of receptor sites was lower (R0 = 0.046 +/- 0.006 nmol/l equivalent to 6.3 +/- 0.8 receptors/erythrocyte) with [mono-125I-(Tyr A 14)]insulin as compared to [125I]insulin randomly iodinated by the chloramine-T method (R0 = 0.070 +/- 0.008 nmol/l equivalent to 9.6 +/- 1.1 receptors/erythrocyte). Conversely, the affinity of the [mono-125I-(Tyr A 14)]insulin was higher (Ka = 2.6 +/- 0.3 x 10(9) l . mol-1 vs. 1.9 +/- 0.2 x 10(9) l . mol-1.
Adult↗
Characterization of angiotensin receptors on bovine adrenal fasciculata cells.
We have further characterized angiotensin receptors on bovine adrenal fasciculata cells whose presence was previously demonstrated by the intrinsic agonistic activity of angiotensin II (AII), dex-Asp1-AII, angiotensin I (AI), and des-ASp1-AI on steroidogenesis. The specific binding of AII and des-Asp1-AII labeled with 125I to dispersed bovine fasciculata cells was studied. For both peptides, a single class of binding sites accounted for the data with a mean (+/- SEM) Ka value of 0.23 +/- 0.123 X 10(8) liters/mol for AII and 0.68 X 10(8) liters/mol for des-Asp1-AII. The concentration at which unlabeled AII and des-Asp1-AII displaced 50% of the tracers (Kd) was similar to that at which they induced half-maximal stimulation of steroidogenesis (Kact). For AI and des-Asp1-AI, Kd greater than Kact. Analogs of AII or des-Asp1-AII with antagonistic properties upon steroidogenesis competed also with binding of the tracers. Corticotropin (ACTH) did not inhibit binding. Although ACTH stimulated the formation of cyclic AMP, none of the angiotensins with intrinsic activity did so. Calcium, but not potassium, appeared to potentiate the steroidogenic activity of AII. These data suggest that there is a single class of receptors for angiotensins and analogs in zona fasciculata. These receptors show characteristics that differentiate them from ACTH receptors in zona fasciculata or angiotensin receptors in zona glomerulosa cells.
Adrenal Cortex↗
Stimulation of corticosteroid biosynthesis by angiotensin I [des-asp1]angiotensin I, angiotensin II and [des-asp1]-angiotensin II in bovine adrenal fasciculata cells.
The effect of angiotensin I (AI), angiotensin II (AII), [des-asp1]AI, [des-asp1]AII and [des-asp1-arg2]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied. AII and [des-asp1]AII in concentrations ranging from 10(-9)M to 10(-6)M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than AII and [des-asp1]AII. The effect of AI was not due to its conversion to AII. [Des-asp1]AI was as active as AI. No significant conversion to [des-asp1]AII was observed. [Des-asp1-arg2]AII had only a minimal effect on steroidogenesis. The structural analog [sar1,-ala8]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for AII and [des-asp1]AII than for [sar1,ala8]ALL, but lower for AI and [des-asp1]AI than for the inhibitor. Combination of submaximal doses of AI and AII resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as AII alone. These data demonstrate a potent steroidogenic activity for AII as well as AI, [des-asp1]AI and [des-asp1]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested.
Adrenal Cortex Hormones↗
Stimulating effects of angiotensin I, angiotensin II and des-Asp1-angiotensin II on steroid production in vitro and its inhibition by Sar1-Ala8-angiotensin II.
Two of the agents known to block the renin-angiotensin-aldosterone system, namely Sar1-Ala8-angiotensin II and the nonapeptide SQ 20881, have been used to clarify the role of angiotensin II (AII) and its cogeners upon the steroidogenesis in isolated fasciculata cells from bovine adrenal tissue. It could be concluded that: (1) des-Asp1-angiotensin II is as active as AII on steroidogenesis from bovine fasciculata cells; (2) angiotensin I, although less potent, stimulates steroid production without being converted to AII or des-Asp1-AII, and (3) Sar1-Ala8-AII inhibits all three peptides in a competitive manner. The presence of a common receptor for all these three peptides is suggested.
Adrenal Cortex Hormones↗
Effects of varying sodium intake on blood pressure and renin-angiotensin system in subtotally nephrectomized rats.
In rats in which the renal mass had been reduced by 70 per cent, the effects of varying sodium intake on blood pressure, serum electrolytes, renin-angiotensin system, and some other parameters that were modified simultaneously were studied. Within 4 weeks, a high sodium diet (750 mEa. per kilogram) resulted in marked hypertension, whereas a standard sodium diet (150 mEq. per kilogram) elevated the blood pressure only slightly. A low sodium diet (less than 0.2 mEq. per kilogram) prevented the rise in blood pressure. In the hypertensive group, the hematocrit values were markedly decreased, indicating the expansion of extracellular and intravascular spaces. The compensatory renal hypertrophy was accelerated by the high sodium diet and retarded during restriction. During low sodium intake, the serum concentration of sodium was diminished and that of potassium elevated. During the high sodium diet, the sodium concentration was unchanged, but the potassium concentration was decreased. Subtotal nephrectomy diminished the plasma angiotensin II concentration, and the renin content of the kidney remnant was lower than that of the kidneys from control animals. Sodium restriction stimulated the renin angiotensin system markedly, whereas high sodium intake suppressed it. After subtotal nephrectomy, elevation of blood pressure, renal hypertrophy, and suppression of the renin-angiotensin system are closely related to sodium intake.
Angiotensin II↗
ABO blood groups and chicken pox.
In 974 patients with chicken pox (varicellae) from four large children's hospitals in Germany, a weak association with blood groups A (and probably AB) was found.
ABO Blood-Group System↗
Arterial hypertension induced by 9 alpha-fluorocortisol in rats.
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Angiotensin II↗