scholarly journals Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions

2020 ◽  
Vol 21 (4) ◽  
pp. 1182 ◽  
Author(s):  
Kazuo Hosoi ◽  
Chenjuan Yao ◽  
Takahiro Hasegawa ◽  
Hiroshi Yoshimura ◽  
Tetsuya Akamatsu
Keyword(s):  
Salivary Gland ◽  
Constitutive Expression ◽  
Lateral Diffusion ◽  
Mitogen Activated Protein Kinase ◽  
Amylase Secretion ◽  
Activator Protein 1 ◽  
Aquaporin 5 ◽  
Parasympathetic Nerve ◽  
Mitogen Activated Protein ◽  
Aqp5 Expression

Aquaporin 5 (AQP5) plays an important role in the salivary gland function. The mRNA and protein for AQP5 are expressed in the acini from embryonic days E13-16 and E17-18, respectively and for entire postnatal days. Ligation-reopening of main excretory duct induces changes in the AQP5 level which would give an insight for mechanism of regeneration/self-duplication of acinar cells. The AQP5 level in the submandibular gland (SMG) decreases by chorda tympani denervation (CTD) via activation autophagosome, suggesting that its level in the SMG under normal condition is maintained by parasympathetic nerve. Isoproterenol (IPR), a β-adrenergic agonist, raised the levels of membrane AQP5 protein and its mRNA in the parotid gland (PG), suggesting coupling of the AQP5 dynamic and amylase secretion-restoration cycle. In the PG, lipopolysaccharide (LPS) is shown to activate mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalings and potentially downregulate AQP5 expression via cross coupling of activator protein-1 (AP-1) and NF-κB. In most species, Ser-156 and Thr-259 of AQP5 are experimentally phosphorylated, which is enhanced by cAMP analogues and forskolin. cAMP-dependent phosphorylation of AQP5 does not seem to be markedly involved in regulation of its intracellular trafficking but seems to play a role in its constitutive expression and lateral diffusion in the cell membrane. Additionally, Ser-156 phosphorylation may be important for cancer development.

scholarly journals Porphyromonas gingivalis Induces Receptor Activator of NF-κB Ligand Expression in Osteoblasts through the Activator Protein 1 Pathway

2004 ◽  
Vol 72 (3) ◽  
pp. 1706-1714 ◽  
Author(s):  
Nobuo Okahashi ◽  
Hiroaki Inaba ◽  
Ichiro Nakagawa ◽  
Taihei Yamamura ◽  
Masae Kuboniwa ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Porphyromonas Gingivalis ◽  
Bone Destruction ◽  
Cysteine Proteases ◽  
Mitogen Activated Protein Kinase ◽  
Activator Protein 1 ◽  
Rankl Expression ◽  
Activator Protein ◽  
Receptor Activator ◽  
Mitogen Activated Protein

ABSTRACT Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption, and several components of the organism such as lipopolysaccharides have been reported to stimulate production of cytokines that promote inflammatory bone destruction. We investigated the effect of infection with viable P. gingivalis on cytokine production by osteoblasts. Reverse transcription-PCR and real-time PCR analyses revealed that infection with P. gingivalis induced receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) mRNA expression in mouse primary osteoblasts. Production of interleukin-6 was also stimulated; however, osteoprotegerin was not. SB20350 (an inhibitor of p38 mitogen-activated protein kinase), PD98059 (an inhibitor of classic mitogen-activated protein kinase kinase, MEK1/2), wortmannin (an inhibitor of phosphatidylinositol 3 kinase), and carbobenzoxyl-leucinyl-leucinyl-leucinal (an inhibitor of NF-κB) did not prevent the RANKL expression induced by P. gingivalis. Degradation of inhibitor of NF-κB-alpha was not detectable; however, curcumin, an inhibitor of activator protein 1 (AP-1), prevented the RANKL production induced by P. gingivalis infection. Western blot analysis revealed that phosphorylation of c-Jun, a component of AP-1, occurred in the infected cells, and an analysis of c-Fos binding to an oligonucleotide containing an AP-1 consensus site also demonstrated AP-1 activation in infected osteoblasts. Infection with P. gingivalis KDP136, an isogenic deficient mutant of arginine- and lysine-specific cysteine proteinases, did not stimulate RANKL production. These results suggest that P. gingivalis infection induces RANKL expression in osteoblasts through AP-1 signaling pathways and cysteine proteases of the organism are involved in RANKL production.

Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression

2001 ◽  
Vol 281 (4) ◽  
pp. L766-L775 ◽  
Author(s):  
Isabel Carreras ◽  
Celeste B. Rich ◽  
Julie A. Jaworski ◽  
Sandra J. Dicamillo ◽  
Mikhail P. Panchenko ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Activator Protein 1 ◽  
Fibroblast Growth ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Elastin Gene

Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.

scholarly journals Phosphoprotein Enriched in Astrocytes-15 kDa Expression Inhibits Astrocyte Migration by a Protein Kinase Cδ-dependent Mechanism

2006 ◽  
Vol 17 (12) ◽  
pp. 5141-5152 ◽  
Author(s):  
François Renault-Mihara ◽  
Frédéric Beuvon ◽  
Xavier Iturrioz ◽  
Brigitte Canton ◽  
Sophie De Bouard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fluorescent Protein ◽  
Constitutive Expression ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Bryostatin 1 ◽  
Calcium Calmodulin Dependent ◽  
Mitogen Activated Protein ◽  
Green Fluorescent

Phosphoprotein enriched in astrocytes-15 kDa (PEA-15), a phosphoprotein enriched in astrocytes, inhibits both apoptosis and proliferation in normal and cancerous cells. Here, analysis of PEA-15 expression in glioblastoma organotypic cultures revealed low levels of PEA-15 in tumor cells migrating away from the explants, regardless of the expression levels in the originating explants. Because glioblastomas are highly invasive primary brain tumors that can originate from astrocytes, we explored the involvement of PEA-15 in the control of astrocyte migration. PEA-15−/− astrocytes presented an enhanced motility in vitro compared with their wild-type counterparts. Accordingly, NIH-3T3 cells transfected by green fluorescent protein-PEA-15 displayed a reduced migration. Reexpression of PEA-15 restored PEA-15−/− astrocyte motility to wild-type levels. Pharmacological manipulations excluded a participation of extracellular signal-regulated kinase/mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt, and calcium/calmodulin-dependent protein kinase II in this effect of PEA-15. In contrast, treatment by bisindolylmaleimide, Gö6976, and rottlerin, and chronic application of phorbol 12-myristate 13-acetate and/or bryostatin-1 indicated that PKCδ mediated PEA-15 inhibition of astrocyte migration. PEA-15−/− astrocytes constitutively expressed a 40-kDa form of PKCδ that was down-regulated upon PEA-15 reexpression. Together, these data reveal a new function for PEA-15 in the inhibitory control of astrocyte motility through a PKCδ-dependent pathway involving the constitutive expression of a catalytic fragment of PKCδ.

scholarly journals Insulin-mediated activation of activator protein-1 through the mitogen-activated protein kinase pathway stimulates collagenase-1 gene transcription in the MES 13 mesangial cell line

2004 ◽  
Vol 33 (1) ◽  
pp. 263-280 ◽  
Author(s):  
JE Ayala ◽  
JN Boustead ◽  
SC Chapman ◽  
CA Svitek ◽  
JK Oeser ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Line ◽  
Gene Transcription ◽  
Fusion Gene ◽  
Mitogen Activated Protein Kinase ◽  
Potential Contribution ◽  
Activator Protein 1 ◽  
Promoter Elements ◽  
Activator Protein ◽  
Mitogen Activated Protein

The initial stages of diabetic nephropathy are characterized, in part, by expansion of the mesangial matrix and thickening of the glomerular basement membrane which are caused by increased extracellular matrix (ECM) protein synthesis and reduced degradation, a consequence of decreased matrix metalloproteinase (MMP) activity. These changes have been largely attributed to the effects of hyperglycemia such that the potential contribution of impaired insulin action to alterations in the ECM have not been studied in detail. We have shown here that insulin stimulates collagenase-1 fusion gene transcription in the MES 13 mesangial-derived cell line. Multiple collagenase-1 promoter elements are required for the full stimulatory effect of insulin but the action of insulin appears to be mediated through an activator protein-1 (AP-1) motif. Thus, mutation of this AP-1 motif abolishes insulin-stimulated collagenase fusion gene transcription and, in isolation, this AP-1 motif can mediate a stimulatory effect of insulin on the expression of a heterologous fusion gene. This suggested that the other collagenase-1 promoter elements that are required for the full stimulatory effect of insulin probably bind accessory factors that enhance the effect of insulin mediated through the AP-1 motif. In MES 13 cells, the AP-1 motif is bound by Fra-1, Fra-2, Jun B and Jun D. Stimulation of collagenase-1 fusion gene transcription by insulin requires activation of the mitogen-activated protein kinase (MEK) pathway since inhibition of MEK-1 and -2 blocks this effect. The potential significance of these observations with respect to a role for insulin in the pathophysiology of diabetic glomerulosclerosis is discussed.

scholarly journals p38 Mitogen-Activated Protein Kinase Is Critical for Synergistic Induction of the FSHβ Gene by Gonadotropin-Releasing Hormone and Activin through Augmentation of c-Fos Induction and Smad Phosphorylation

2007 ◽  
Vol 21 (12) ◽  
pp. 3071-3086 ◽  
Author(s):  
Djurdjica Coss ◽  
Cameron M. Hand ◽  
Karen K. J. Yaphockun ◽  
Heather A. Ely ◽  
Pamela L. Mellon
Keyword(s):  
P38 Mapk ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Limiting Factor ◽  
Activator Protein 1 ◽  
Mapk Activity ◽  
C Terminus ◽  
Smad Phosphorylation ◽  
Mitogen Activated Protein ◽  
Smad 3

Abstract GnRH and activin independently and synergistically activate transcription of the FSH β-subunit gene, the subunit that provides specificity and is the limiting factor in the synthesis of the mature hormone. This synergistic interaction, as determined by two-way ANOVA, is specific for FSHβ and may, therefore, contribute to differential expression of the two gonadotropin hormones, which is critical for the reproductive cycle. We find that the cross-talk between the GnRH and activin signaling pathways occurs at the level of p38 MAPK, because the synergy is dependent on p38 MAPK activity, which is activated by GnRH, and activin cotreatment augments p38 activation by GnRH. Both the Smad and activator protein-1 binding sites on the FSHβ promoter are necessary and sufficient for synergy. After cotreatment, Smad 3 proteins are more highly phosphorylated on the activin-receptor signaling-dependent residues on the C terminus than with activin treatment alone, and c-Fos is more highly expressed than with GnRH treatment alone. Inhibition of p38 by either of two different inhibitors or a dominant-negative p38 kinase abrogates synergy on FSHβ expression, reduces c-Fos induction by GnRH, and prevents the further increase in c-Fos levels that occurs with cotreatment. Additionally, p38 is necessary for maximal Smad 3 C-terminal phosphorylation by activin treatment alone and for the further increase caused by cotreatment. Thus, p38 is the pivotal signaling molecule that integrates GnRH and activin interaction on the FSHβ promoter through higher induction of c-Fos and elevated Smad phosphorylation.

scholarly journals Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

2004 ◽  
Vol 2004 (5) ◽  
pp. 321-325 ◽  
Author(s):  
De-Xing Hou ◽  
Makoto Fujii ◽  
Norihiko Terahara ◽  
Makoto Yoshimoto
Keyword(s):  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Cell Transformation ◽  
Mapk Pathway ◽  
Animal Experiments ◽  
Cancer Chemoprevention ◽  
Mitogen Activated Protein Kinase ◽  
Blue Color ◽  
Activator Protein 1 ◽  
Mitogen Activated Protein

Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i) inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK) pathway and activator protein 1 (AP-1) factor; (ii) suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factorkappaB (NF-κB) pathway andcyclooxygenase2 (COX-2) gene; (iii) apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS) / c-Jun NH2-terminal kinase (JNK)-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention.

scholarly journals Dietary Suberic Acid Protects Against UVB-Induced Skin Photoaging in Hairless Mice

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2948 ◽  
Author(s):  
Wesuk Kang ◽  
Dabin Choi ◽  
Taesun Park
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Collagen Type I ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Activator Protein 1 ◽  
Suberic Acid ◽  
Hairless Mice ◽  
Mitogen Activated Protein ◽  
Skin Photoaging

Ultraviolet (UV) radiation is a major cause of skin photoaging, which is mainly characterized by dryness and wrinkle formation. In the current study, we investigated the anti-photoaging effects of dietary suberic acid, a naturally occurring photochemical, using UVB-irradiated hairless mice. Mice were exposed to UVB three times weekly and fed diets containing three different suberic acid concentrations (0.05%, 0.1% and 0.2%) for 10 weeks. It was found that suberic acid inhibited UVB-induced skin dryness, wrinkle formation, and epidermal thickness in hairless mice. In parallel with phenotypic changes, suberic acid attenuated UVB-induced matrix metalloproteinase (MMP) genes (MMP1a, MMP1b, MMP3, and MMP9), while accelerating collagen genes including collagen type I alpha 1 chain (COL1A1), COL1A2, and COL3A1 and hyaluronic acid synthases genes (HAS1, HAS2 and HAS3). We further demonstrated that suberic acid upregulated the molecules involved in the transforming growth factor–β (TGF-β)/SMAD pathway, but downregulated the molecules participating in the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling in UVB-irritated hairless mice. Collectively, we propose that suberic acid may be a promising agent for treating skin photoaging.

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