Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

Although vgf gene knockout mice are hypermetabolic, administration of the VGF peptide TLQP-21 itself increased energy consumption. Agonist–antagonist roles are thus suggested for different VGF peptides, and the definition of their tissue heterogeneity is mandatory. We studied the rat stomach using antisera to C- or N-terminal sequences of known or predicted VGF peptides in immunohistochemistry and ELISA. TLQP (rat VGF556–565) peptide/s were most abundant (162±11 pmol/g, mean±s.e.m.) and were brightly immunostained in enterochromaffin-like (ECL) cells and somatostatin cells. A peptide co-eluting with TLQP-21 was revealed in HPLC of gastric and hypothalamic extracts, while the extended TLQP-62 form was restricted to the hypothalamus. Novel PGH (rat VGF422–430) peptide/s were revealed in ghrelin cells, mostly corresponding to low MW forms (0.8–1.5 kDa), while VGF C-terminus peptides were confined to neurons. VGF mRNA was present in the above gastric endocrine cell types, and was prominent in chief cells, in parallel with low-intensity staining for further cleaved products from the C-terminal region of VGF (HVLL peptides: VGF605–614). In swine stomach, a comparable profile of VGF peptides was revealed by immunohistochemistry. When fed and fasted rats were studied, a clear-cut, selective decrease on fasting was observed for TLQP peptides only (162±11 vs 74±5.3 pmol/g, fed versus fasted rats, mean±s.e.m., P<0.00001). In conclusion, specific VGF peptides appear to be widely represented in different gastric endocrine and other mucosal cell populations. The selective modulation of TLQP peptides suggests their involvement in peripheral neuro-endocrine mechanisms related to feeding responses and/or ECL cell regulation.

Download Full-text

Fasting-induced changes in ECL cell gene expression

Physiological Genomics ◽

10.1152/physiolgenomics.00252.2006 ◽

2007 ◽

Vol 31 (2) ◽

pp. 183-192 ◽

Cited By ~ 8

Author(s):

Nils W. G. Lambrecht ◽

Iskandar Yakubov ◽

George Sachs

Keyword(s):

Gene Expression ◽

Protein Content ◽

Quantitative Polymerase Chain Reaction ◽

Cell Types ◽

Mucosal Cell ◽

Ecl Cells ◽

Ecl Cell ◽

Histamine Uptake ◽

Cell Gene Expression ◽

Fasted Rats

Gastric enterochromaffin-like (ECL) cells release histamine in response to food because of elevation of gastrin and neural release of pituitary adenylate cyclase-activating peptide (PACAP). Acid secretion is at a basal level in the absence of food but is rapidly stimulated with feeding. Rats fasted for 24 h showed a significant decrease of mucosal histamine despite steady-state expression of the histamine-synthesizing enzyme histamine decarboxylase (HDC). Comparative transcriptomal analysis using gene expression oligonucleotide microarrays of 95% pure ECL cells from fed and 24-h fasted rats, thereby eliminating mRNA contamination from other gastric mucosal cell types, identified significantly increased gene expression of the enzymes histidase and urocanase catabolizing the HDC substrate l-histidine but significantly decreased expression of the cellular l-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2 (VMAT-2) responsible for histamine uptake into secretory vesicles. This was confirmed by reverse transcriptase-quantitative polymerase chain reaction of gastric fundic mucosal samples from fed and 24-h fasted rats. The decrease of VMAT-2 gene expression was also shown by a decrease in VMAT-2 protein content in protein extracts from fed and 24-h fasted rats compared with equal amounts of HDC protein and Na-K-ATPase α1-subunit protein content. These results indicate that rat gastric ECL cells regulate their histamine content during 24-h fasting not by a change in HDC gene or protein expression but by regulation of substrate concentration for HDC and a decreased histamine secretory pool.

Download Full-text

Differential distribution of VGF-derived peptides in the adrenal medulla and evidence for their selective modulation

Journal of Endocrinology ◽

10.1677/joe-07-0346 ◽

2008 ◽

Vol 197 (2) ◽

pp. 359-369 ◽

Cited By ~ 20

Author(s):

Filomena D'Amato ◽

Barbara Noli ◽

Carla Brancia ◽

Cristina Cocco ◽

Giovanna Flore ◽

...

Keyword(s):

Gene Knockout ◽

Gel Chromatography ◽

Similar Response ◽

Differential Distribution ◽

Swimming Stress ◽

C Terminus ◽

Gene Knockout Mice ◽

Bona Fide ◽

Major Increase ◽

Regulatory Effects

While vg f gene knockout mice are hyperactive and hypermetabolic, surprisingly the TLQP-21 brain VGF peptide increased energy consumption, suggesting that opposing regulatory effects could be exerted by peptides alternatively cleaved from the VGF precursor. Using antisera to the VGF precursor C-terminus and three cleavage products, we revealed a distinct differential distribution in adrenal, certain peptides (VGF422–430: PGH peptides) being found throughout bovine and swine medulla, while C-terminus and TLQP peptides were confined to adrenaline cells in the above species and in rat and C-terminally shortened forms (VGF604–612: HVLL peptides) to nor-adrenaline cells. Random abattoir samples of bovine and swine adrenal contained 520±40 and 450±60 pmol/g (mean±s.e.m. respectively) of C-terminus peptides and similar or lower amounts of others. Upon gel chromatography, bona fide VGF precursor, ~7.5 and ~3.5 kDa forms were revealed by C-terminus assays, HVLL peptides being limited to small fragments. TLQP peptides included ~7.5 kDa form and peaks accounting for TLQP-21 and predicted TLQP-30 and TLQP-42. Low molecular weight (MW) PGH peptides were revealed, together with a high MW form possibly encompassing the VGF precursor N-terminus. In acutely stressed swine, a striking increase was seen for C-terminus and TLQP peptides, with no significant differences for PGH peptides. A similar response was found in rat TLQP peptides showing a major increase upon an acute swimming stress and 30 min thereafter. A differential processing of the VGF precursor encompassing many areas of its primary sequence and selective modulations of its derived peptides occur in adrenal medullary cells, possibly relevant to adaptive homeostatic responses.

Download Full-text

Study about the Expression of CypA Proteins and Its Blocking Effect in the Cerebellum from FMR1 Gene Knockout Mice by Electroacupuncture of DU1 Acupoint

Rehabilitation Medicine ◽

10.3724/sp.j.1329.2017.05029 ◽

2017 ◽

Vol 27 (5) ◽

pp. 29

Author(s):

Dong LIN ◽

Wanping BU ◽

Xiaoting YANG

Keyword(s):

Knockout Mice ◽

Gene Knockout ◽

Blocking Effect ◽

Fmr1 Gene ◽

Gene Knockout Mice

Download Full-text

Detrimental implication of B1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

International Immunopharmacology ◽

10.1016/s1567-5769(02)00022-x ◽

2002 ◽

Vol 2 (6) ◽

pp. 815-822 ◽

Cited By ~ 47

Author(s):

Caroline Lagneux ◽

Michael Bader ◽

João B. Pesquero ◽

Pierre Demenge ◽

Christophe Ribuot

Keyword(s):

Myocardial Ischemia ◽

Knockout Mice ◽

Gene Knockout ◽

B1 Receptors ◽

Gene Knockout Mice ◽

Pharmacological Blockade

Download Full-text

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice

Neuropharmacology ◽

10.1016/j.neuropharm.2006.05.003 ◽

2006 ◽

Vol 51 (3) ◽

pp. 612-622 ◽

Cited By ~ 27

Author(s):

Jalal Izadi Mobarakeh ◽

Kazuhiro Takahashi ◽

Shinobu Sakurada ◽

Atsuo Kuramasu ◽

Kazuhiko Yanai

Keyword(s):

Knockout Mice ◽

Gene Knockout ◽

Receptor Gene ◽

Histamine H2 Receptor ◽

H2 Receptor ◽

Antinociceptive Effects ◽

Gene Knockout Mice

Download Full-text

Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)30162-0 ◽

2002 ◽

Vol 43 (2) ◽

pp. 205-214 ◽

Cited By ~ 3

Author(s):

Brett Garner ◽

David A. Priestman ◽

Roland Stocker ◽

David J. Harvey ◽

Terry D. Butters ◽

...

Keyword(s):

Apolipoprotein E ◽

Knockout Mice ◽

Gene Knockout ◽

E Gene ◽

Apolipoprotein E Gene ◽

Gene Knockout Mice

Download Full-text

Exploring International and Inter-Sector Differences of Social Enterprises in the UK and India

Sustainability ◽

10.3390/su13115870 ◽

2021 ◽

Vol 13 (11) ◽

pp. 5870

Author(s):

Philipp Kruse

Keyword(s):

Social Entrepreneurship ◽

Social Enterprise ◽

Social Enterprises ◽

Future Research ◽

Shape Features ◽

Qualitative And Quantitative ◽

Clear Cut ◽

The One ◽

Definition Of ◽

The Uk

Social Entrepreneurship (SE) describes a new entrepreneurial form combining the generation of financial and social value. In recent years, research interest in SE increased in various disciplines with a particular focus on the characteristics of social enterprises. Whereas a clear-cut definition of SE is yet to be found, there is evidence that culture and economy affect and shape features of SE activity. In addition, sector-dependent differences are supposed. Building on Institutional Theory and employing a mixed qualitative and quantitative approach, this study sheds light on the existence of international and inter-sector differences by examining 161 UK and Indian social enterprises. A content analysis and analyses of variance were employed and yielded similarities as well as several significant differences on an international and inter-sector level, e.g., regarding innovativeness and the generation of revenue. The current study contributes to a more nuanced picture of the SE landscape by comparing social enterprise characteristics in a developed and a developing country on the one hand and different sectors on the other hand. Furthermore, I highlight the benefits of jointly applying qualitative and quantitative methodologies. Future research should pay more attention to the innate heterogeneity among social enterprises and further consolidate and extend these findings.

Download Full-text

Desmosomal Molecules In and Out of Adhering Junctions: Normal and Diseased States of Epidermal, Cardiac and Mesenchymally Derived Cells

Dermatology Research and Practice ◽

10.1155/2010/139167 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 17

Author(s):

Sebastian Pieperhoff ◽

Mareike Barth ◽

Steffen Rickelt ◽

Werner W. Franke

Keyword(s):

Cell Biology ◽

Cell Types ◽

Cell Junctions ◽

Surface Molecules ◽

Transmembrane Glycoprotein ◽

Current Cell ◽

Plakophilin 2 ◽

Definition Of ◽

Adhering Junctions ◽

Cell Cell

Current cell biology textbooks mention only two kinds of cell-to-cell adhering junctions coated with the cytoplasmic plaques: the desmosomes (maculae adhaerentes), anchoring intermediate-sized filaments (IFs), and the actin microfilament-anchoring adherens junctions (AJs), including both punctate (puncta adhaerentia) and elongate (fasciae adhaerentes) structures. In addition, however, a series of other junction types has been identified and characterized which contain desmosomal molecules but do not fit the definition of desmosomes. Of these special cell-cell junctions containing desmosomal glycoproteins or proteins we review the composite junctions (areae compositae) connecting the cardiomyocytes of mature mammalian hearts and their importance in relation to human arrhythmogenic cardiomyopathies. We also emphasize the various plakophilin-2-positive plaques in AJs (coniunctiones adhaerentes) connecting proliferatively active mesenchymally-derived cells, including interstitial cells of the heart and several soft tissue tumor cell types. Moreover, desmoplakin has also been recognized as a constituent of the plaques of thecomplexus adhaerentesconnecting certain lymphatic endothelial cells. Finally, we emphasize the occurrence of the desmosomal transmembrane glycoprotein, desmoglein Dsg2, out of the context of any junction as dispersed cell surface molecules in certain types of melanoma cells and melanocytes. This broadening of our knowledge on the diversity of AJ structures indicates that it may still be too premature to close the textbook chapters on cell-cell junctions.

Download Full-text

The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice

Biomedicines ◽

10.3390/biomedicines9070840 ◽

2021 ◽

Vol 9 (7) ◽

pp. 840

Author(s):

Qiaofeng Zhao ◽

Satoshi Koyama ◽

Nagisa Yoshihara ◽

Atsushi Takagi ◽

Etsuko Komiyama ◽

...

Keyword(s):

Alopecia Areata ◽

Gene Knockout ◽

Stress Test ◽

Coiled Coil ◽

Risk Haplotype ◽

Gene Expression Microarray ◽

Wild Type ◽

Gene Knockout Mice ◽

Deficient Mice ◽

Gene Expression Microarray Analysis

We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype. We also reported that the engineered mice with this risk allele exhibited. To investigate more about the involvement of the CCHCR1 gene in AA pathogenesis, we developed an AA model using C57BL/6N cchcr1 gene knockout mice. In this study, mice (6–8 weeks) were divided into two groups: cchcr1−/− mice and wild-type (WT) littermates. Both groups were subjected to a water avoidance stress (WAS) test. Eight weeks after the WAS test, 25% of cchcr1−/− mice exhibited non-inflammatory foci of alopecia on the dorsal skin. On the other hand, none of wild-type littermates cause hair loss. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings. Additionally, gene expression microarray analysis of cchcr1−/− mice revealed abnormalities of hair related genes compared to the control. Our results strongly suggest that CCHCR1 is associated with AA pathogenesis and that cchcr1−/− mice are a good model for investigating AA.

Download Full-text