Cellular and subcellular colocalization of nerve growth factor and epidermal growth factor in mouse submandibular glands

Watson, Ann Y.; Anderson, John; Siminoski, Kerry; Mole, John E.; Murphy, Richard A.

doi:10.1002/ar.1092130302

Cited by 54 publications

(24 citation statements)

References 47 publications

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“…Vesicles containing zinc ions are found in many secretory cells, e.g. Paneth cells (Dinsdale 1984), submandibular salivary cells in male mice (Watson et al, 1985;Frederickson et al, 1987), the prostatic cells (Eddy, 1988;Sorensen et al, 1996), and not the least in the zinc enriched (ZEN) neurons of the central nervous system (Frederickson & Danscher, 1990).…”

Section: Discussionmentioning

confidence: 99%

Histochemical localization of zinc ions in the epididymis of the rat

et al. 1996

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In the present study, the autometallograpic zinc sulphide technique, an improved version of the original Timm sulphide-silver method, was used. This technique reveals a particular pool of ionic zinc that is chelatable by diethyldithiocarbamate. At the light microscopical level, no reaction for zinc was found in tissues of young prepubertal rats. In adult mating and non-mating rats low zinc staining was found in the head and intermediate epididymis whereas the tail of the epididymis demonstrated high levels of zinc ions. Sections from the epididymal tail revealed a 'compartmentalization', based on pronounced differences in staining intensity along the epididymal ducts. At higher magnification zinc ions were found in the apical part of the principal cell and in the lumen. At the ultrastructural level autometallographic grains were located in vesicles and in lysosome-like structures of the apical parts of the principal cells. The luminal grains were found either associated with sperm cells, with the surface of the large microvilli (stereocilia), or free in the seminal fluid. The variation in content of zinc ions in the epididymal epithelium and lumen suggests that zinc ions are secreted into the lumen from the epididymal tail and may somehow be involved in maturation of the sperm cells.

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Section: Discussionmentioning

confidence: 99%

Histochemical localization of zinc ions in the epididymis of the rat

et al. 1996

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“…In both series of experiments, we used TGF-a that had been synthesized by a modification ofthe method of Merrifield and has been characterized previously (9,16). EGF was isolated from male mouse submandibular glands by the method of Savage and Cohen (23) and its purity was characterized earlier (24). Data were analyzed by two-way (animal and treatment) analysis of variance (ANOVA) and (where appropriate) by Tukey's range test, using the SAS statistical system (SAS Institute, Cary, NC) run on an IBM 4341 computer.…”

Section: Methodsmentioning

confidence: 99%

Transforming growth factor alpha inhibits secretion of gastric acid.

Rhodes¹,

Tam²,

Finke³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Transforming growth factor a (TGF-a), a protein secreted by transformed cells and related to epidermal growth factor (EGF), was tested for its effects on gastric acid secretion. Guinea pig gastric mucosae were mounted in Ussing chambers and the rate of acid release was monitored by the pH-stat method. When administered prior to the secretagogue, TGF-a prevented the histamine-induced increase in the rate of acid secretion. Similarly, TGF-a caused a decrease in the rate of acid release in tissues that had already been stimulated with histamine. These data show that TGF-a inhibits gastric acid secretion in a manner similar to EGF and that the two growth factors share at least one physiological action unrelated to their mitogenic properties.Transforming growth factor a (TGF-a) is a protein that is structurally and functionally similar to epidermal growth factor (EGF). The overall amino acid sequences of these two peptides are about 33% homologous, and there is an even more highly conserved core region (1-4). TGF-a competes with EGF for binding to a receptor on the surface of cultured cells and isolated membranes (5-10), and an antibody to the EGF receptor blocks the mitogenic activity of conditioned medium containing TGF-a (11). TGF-a (or a partially purified preparation containing TGF-a) stimulates phosphorylation of tyrosine residues on the EGF receptor and other substrates (9, 12, 13). TGF-a, like EGF, is mitogenic for cultured cells (5,9,14) and in conjunction with transforming growth factor f3 permits anchorage-independent growth of NRK cells (7-10). In vivo, both TGF-a and EGF cause precocious separation of eyelids of newborn mice (15,16).In addition to these growth-related phenomena, EGF is known to inhibit gastric acid secretion (17-22). We have previously (22) used an Ussing-chamber preparation of guinea pig mucosae to study EGF's antisecretory properties. This system has the advantages over whole-animal models that the concentrations oftest substances can be precisely controlled, that secondary effects arising from interaction of the test substances with other organs are eliminated, and that much smaller quantities of reagents are required. These properties make the in vitro guinea pig model ideal for studying the effects of peptides related to EGF.One possible explanation for the coexistence of EGF and TGF-a is that, besides their shared mitogenic properties, they might also have biological activities unique to each peptide. To determine whether inhibition of acid secretion is one of these unique properties, we examined the effect of TGF-a on the Ussing-chamber preparation of guinea pig mucosa. We report here that TGF-a is capable of inhibiting histaminestimulated acid secretion in a manner similar to EGF. MATERIALS AND METHODSStomachs from young (200-to 250-g) female guinea pigs were hemisected along the greater and lesser curvatures and placed mucosal-surface down on a piece of Parafilm. The outer muscle layers were removed with fine forceps and both halves of the mucosa were mounted separately ...

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“…The component proteins produced and released into saliva by the salivary glands are grouped according to their functions: lubrication of the oral cavity (mucins, proline-rich proteins), remineralization (statherin, proline-rich proteins), digestion (amylase, lipase, proteases), antimicrobial activity (lysozyme, peroxidases, histatins), and mucosal integrity (water, mucins, growth factors) (1)(2)(3). Biologically active growth factors include epidermal growth factor (EGF) and nerve growth factor (NGF), both of which are synthesized and secreted by the granular convoluted tubule cells of the salivary glands (4,5). Transforming growth factors ␣ and ␤ (6 -8), insulin, IGF-I and -II (9 -12), and fibroblast growth factor (13) have been localized to the ductal cells in salivary glands from which they are actively secreted into saliva.…”

mentioning

confidence: 99%

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

Nagy

Nagashima²,

Cha³

et al. 2001

Diabetes

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Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and ageand sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.

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Cellular and subcellular colocalization of nerve growth factor and epidermal growth factor in mouse submandibular glands

Cited by 54 publications

References 47 publications

Histochemical localization of zinc ions in the epididymis of the rat

Histochemical localization of zinc ions in the epididymis of the rat

Transforming growth factor alpha inhibits secretion of gastric acid.

Reduced Oral Wound Healing in the NOD Mouse Model for Type 1 Autoimmune Diabetes and Its Reversal by Epidermal Growth Factor Supplementation

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