Molecular characterization of prophenoloxidase-1 (PPO1) and the inhibitory effect of kojic acid on phenoloxidase (PO) activity and on the development ofZeugodacus tau(Walker) (Diptera: Tephritidae)

2018 ◽  
Vol 109 (2) ◽  
pp. 236-247 ◽  
Author(s):  
H.-H. Zhang ◽  
M.-J. Luo ◽  
Q.-W. Zhang ◽  
P.-M. Cai ◽  
A. Idrees ◽  
...  
Keyword(s):  
Kojic Acid ◽  
Normal Growth ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Pupal Weight ◽  
Mrna Levels ◽  
Melanin Biosynthesis ◽  
Horticultural Pest ◽  
Inhibition Experiment

AbstractPhenoloxidase (PO) plays a key role in melanin biosynthesis during insect development. Here, we isolated the 2310-bp full-length cDNA of PPO1 fromZeugodacus tau, a destructive horticultural pest. qRT-polymerase chain reaction showed that theZtPPO1transcripts were highly expressed during larval–prepupal transition and in the haemolymph. When the larvae were fed a 1.66% kojic acid (KA)-containing diet, the levels of theZtPPO1transcripts significantly increased by 2.79- and 3.39-fold in the whole larvae and cuticles, respectively, while the corresponding PO activity was significantly reduced; in addition, the larval and pupal durations were significantly prolonged; pupal weights were lowered; and abnormal phenotypes were observed. Anin vitroinhibition experiment indicated that KA was an effective competitive inhibitor of PO inZ. tau. Additionally, the functional analysis showed that 20E could significantly up-regulate the expression ofZtPPO1, induce lower pupal weight, and advance pupation. Knockdown of theZtPPO1gene by RNAi significantly decreased mRNA levels after 24 h and led to low pupation rates and incomplete pupae with abnormal phenotypes during the larval-pupal interim period. These results proved that PO is important for the normal growth ofZ. tauand that KA can disrupt the development of this pest insect.

scholarly journals Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse toPorphyromonas gingivalisLPS

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Yicong Liu ◽  
Zhou Wu ◽  
Xinwen Zhang ◽  
Junjun Ni ◽  
Weixian Yu ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Chronic Periodontitis ◽  
Human Monocyte ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Proinflammatory Mediators ◽  
Raw264.7 Macrophages ◽  
Inflammatory Signals ◽  
The Mean

We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response toPorphyromonas gingivalis (P.g.)LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. Inin vitrostudies,P.g.LPS induced the secretion of TNF-αand IL-1βfrom THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-αand IL-1βin leptomeningeal cells after treatment with the conditioned medium fromP.g.LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment withP.g.LPS alone. Furthermore, the mean mRNA levels of TNF-αand IL-1βin microglia after treatment with the conditioned medium fromP.g.LPS-stimulated leptomeningeal cells were significantly higher than those afterP.g.LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced theP.g.LPS-induced TNF-αand IL-1βproduction by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.

scholarly journals α-1-Anti-trypsin, an inhibitor of renin

1976 ◽  
Vol 153 (2) ◽  
pp. 505-507 ◽  
Author(s):  
S Scharpé ◽  
M Eid ◽  
W Cooreman ◽  
A Lauwers
Keyword(s):  
Human Plasma ◽  
Competitive Inhibition ◽  
Proteinase Inhibitors ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Renin Activity ◽  
Pig Kidney ◽  
Naturally Occurring ◽  
The Hill

A naturally occurring competitive inhibitor of pig kidney renin has been identified in human plasma. The inhibitor was shown to be α-1 anti-trypsin and the effect in vitro on the renin activity was examined. The slope in the Hill plot is compatible with the assumption of one-site competitive inhibition. Other proteinase inhibitors, such as α-2-macroglobulin and C1 inactivator, however, have no inhibitory effect on the renin-angiotensinogen reaction.

scholarly journals BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary

2005 ◽  
Vol 186 (1) ◽  
pp. 109-121 ◽  
Author(s):  
M-O Faure ◽  
L Nicol ◽  
S Fabre ◽  
J Fontaine ◽  
N Mohoric ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10−11 M to 10−9 M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10−9 M BMP-4 both FSH concentration and FSHβ mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHβ mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHβ mRNA and amplified the suppression of FSH release and FSHβ mRNA levels induced by 17β-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

Sox9-dependent transcriptional regulation of the proprotein convertase furin

2007 ◽  
Vol 293 (1) ◽  
pp. C172-C183 ◽  
Author(s):  
Philippe Guimont ◽  
Francine Grondin ◽  
Claire M. Dubois
Keyword(s):  
High Mobility ◽  
Inhibitory Effect ◽  
Nodule Formation ◽  
Mrna Levels ◽  
Paracrine Factor ◽  
Proprotein Convertase ◽  
Hmg Box ◽  
Repressive Effect

The proprotein convertase furin participates in the maturation/bioactivation of a variety of proproteins involved in chondrogenesis events. These include parathyroid hormone-related peptide (PTHrP), an autocrine/paracrine factor that is crucial to both normal cartilage development and cartilage-related pathological processes. Despite the known importance of furin activity in the bioactivation of the polypeptides, the mechanisms that control furin regulation in chondrogenesis remain unknown. To gain insight into the molecular regulation of furin, we used the mouse prechondrogenic ATDC5 cell line, an established in vitro model of cartilage differentiation. Peak expression of both furin mRNA and furin PTHrP maturation was observed during chondrocyte nodule formation stage, an event that correlated with increased mRNA levels of Sox9, a potent high-mobility-group (HMG) box-containing transcription factor required for cartilage formation. Inhibition of furin activity led to a diminution in maturation of PTHrP, suggesting a relationship between Sox9-induced regulation of furin and chondrogenesis events. Transient transfection of Sox9 in nonchondrogenic cells resulted in a marked increase in furin mRNA and in the transactivation of the furin P1A promoter. Direct Sox9 action on the P1A promoter was narrowed down to a critical paired site with Sox9 binding capability in vitro and in vivo. Sox9 transactivation effect was inhibited by L-Sox5 and Sox-6, two Sox9 homologs also expressed in ATDC5 cells. Sox6 inhibitory effect was reduced when using Sox6-HMG-box mutants, indicating a repressive effect through direct HMG-box/DNA binding. Our work suggests a mechanism by which furin is regulated during chondrogenesis. It also adds to the complexity of Sox molecule interaction during gene regulation.

Abstract 305: HDL Antagonizes the Defects in the Lymphatic System that Contribute to the Pathogenesis of Rheumatoid Arthritis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Radjesh Bisoendial ◽  
Wolfgang Weninger ◽  
Francine Petrides ◽  
Fatiha Tabet ◽  
Paul P Tak ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Hypoxic Conditions ◽  
Therapeutic Benefits ◽  
Erosive Arthropathy

Rheumatoid arthritis (RA) is a common inflammatory erosive arthropathy that increases cardiovascular (CV) risk two-fold. Lymphatic dysfunction, a hallmark of chronic inflammation, is considered an attractive target to resolve synovial inflammation. Given the strong vascular anti-inflammatory properties of high-density lipoprotein (HDL) and its key apolipoprotein (apo)A-I, we hypothesized that they may promote inflammation resolution in RA by improving lymphatic endothelial function via up-regulation of the homeobox-containing transcription factor, Prox-1,a key regulator of inflammation-induced lymphangiogenesis (IIL) . Primary human dermal lymphatic endothelial cells (LEC) were treated for 3 days with TNFα (10 ng/mL) or pre-incubated with apoA-I (1.2 mg/mL) for 24 h, followed by TNFα exposure for 3 days. Prox1 mRNA levels were quantified by qPCR. For the tube formation assay, LECs were seeded into a pre-coated Matrigel 24-well plate, and treated with TNFα for 6 h or pre-incubated with apoA-I for 24 h, followed by TNFα exposure for 6 h. Mouse thoracic ducts (TD) were isolated from 2-4 month old C57Bl/6 mice for studying lymphatic vessel (LV) sprouting. TD rings (1 mm) were implanted into a 3-D culture system containing Matrigel under hypoxic conditions and either treated with TNFα, or pre-incubated for 24 h with apoA-I then exposed to TNFα. Incubation with TNFα decreased LEC Prox1 mRNA levels by about 56% (P<0.05). Prior exposure of LECs to apoA-I blocked TNFα-mediated Prox-1 suppression (P<0.05). TNFα also reduced LEC tube formation by about 55% (p<0.05) and completely inhibited LV sprouting from TD rings (p<0.05). ApoA-I protected against TNFα-mediated inhibition of LEC tube formation (44.7±8.1 versus 81.9±15.0% of control; P<0.05) and the inhibitory effect of TNFα on LV sprouting (P<0.05). These results suggest that apoA-I directly regulates IIL by upregulating Prox1 and protecting against TNFα-mediated restriction of lymphatic sprouting and growth in vitro. Hence, raising HDL may provide dual therapeutic benefits in RA by targeting inflammation and reducing cardiovascular risk. New classes of HDL-raising drugs will allow us to study the long term effects of increasing HDL levels on RA progression and CV risk.

Anti-Melanogenic Activity of p-Chlorophenyl Benzyl Ether in α-MSH-Induced Mouse Melanoma B16F10 Cells

2019 ◽  
Vol 819 ◽  
pp. 118-123
Author(s):  
Wassana Riam-Amatakun ◽  
Panupan Limpachayaporn ◽  
Jhoan Rhea L. Pizon ◽  
Praneet Opanasopit ◽  
Nopparat Nuntharatanapon
Keyword(s):  
Kojic Acid ◽  
Positive Association ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Benzyl Ether ◽  
Melanin Content ◽  
Synthetic Compound ◽  
Melanin Biosynthesis ◽  
B16f10 Cells

Melanin is cutaneous pigment which level of its production determines skin complexion. Overproduction of melanin, frequently promoted by UV rays, results in darkening of the skin. Inhibition of tyrosinase activity, a core component in melanin biosynthesis, is one of the mechanisms of depigmenting agents. Hydroquinone and kojic acid are the examples of well-known whitening agents widely used in both pharmaceutical and cosmetic products. However, their adverse effect issues still needed to be overcome. A recent study showed that p-chlorophenyl benzyl ether (Cl-benz), a new synthetic compound, more strongly inhibited mushroom tyrosinase than kojic acid. In the current study, cytotoxicity, anti-melanogenic activity and anti-tyrosinase activity of Cl-benz were performed in mouse B16F10 melanoma cells compared to kojic acid. After 24 h of treatment on B16F10 cells, the cytotoxicity was not observed with Cl-benz and kojic acid. However, after incubation for 48 h, kojic acid at a concentration of 500 μM reduced cell viability less than 50%, whereas Cl-benz-treated cells showed negligible cytotoxicity. For cell-based assay, Cl-benz exhibited inhibitory effect similar to kojic acid. Melanin production in B16F10 cells was suppressed by Cl-benz in a dose dependent manner. One hundred micrograms of Cl-benz decreased melanin content in α-MSH by 66%. Moreover, the percentage of cellular tyrosinase activity of Cl-benz showed positive association with its corresponding melanin content. These results revealed that Cl-benz could inhibit melanogenesis via the mechanism of cellular tyrosinase inhibition. Accordingly, Cl-benz has potential to become a novel skin whitening agent in terms of efficacy and safety.

scholarly journals Inhibitory Effect of the Noncamptothecin Topoisomerase I Inhibitor LMP-400 on Female Mice Models and Human Pheochromocytoma Cells

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4094-4104 ◽  
Author(s):  
Jan Schovanek ◽  
Petra Bullova ◽  
Yasin Tayem ◽  
Alessio Giubellino ◽  
Robert Wesley ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Hypoxia Inducible Factor ◽  
Human Tumor ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Topoisomerase I Inhibitor ◽  
Female Mice ◽  
Topoisomerase 1 ◽  
Protein Levels

Metastatic pheochromocytoma continues to be an incurable disease, and treatment with conventional cytotoxic chemotherapy offers limited efficacy. In the present study, we evaluated a novel topoisomerase I inhibitor, LMP-400, as a potential treatment for this devastating disease. We found a high expression of topoisomerase I in human metastatic pheochromocytoma, providing a basis for the evaluation of a topoisomerase 1 inhibitor as a therapeutic strategy. LMP-400 inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. In a study performed in athymic female mice, LMP-400 demonstrated a significant inhibitory effect on tumor growth with two drug administration regimens. Furthermore, low doses of LMP-400 decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. The HIF-1α decrease resulted in changes in the mRNA levels of HIF-1 transcriptional targets. In vitro, LMP-400 showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. We conclude that LMP-400 has promising antitumor activity in preclinical models of metastatic pheochromocytoma and its use should be considered in future clinical trials.

Inhibition of bovine adrenocortical steroidogenesis by benzodiazepines: a direct effect on microsomal hydroxylation or an inhibition of calcium uptake?

1992 ◽  
Vol 135 (2) ◽  
pp. 361-369 ◽  
Author(s):  
I. Thomson ◽  
R. Fraser ◽  
C. J. Kenyon
Keyword(s):  
Direct Effect ◽  
Calcium Metabolism ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Zona Glomerulosa ◽  
Free Calcium ◽  
Steroid Hydroxylase ◽  
Drug Concentrations ◽  
Ca Uptake

ABSTRACT We have previously reported that benzodiazepines inhibit microsomal steroid hydroxylases. We have now studied their effects at much lower drug concentrations and have also addressed the suggestion that benzodiazepines alter cellular calcium metabolism. We investigated the in-vitro effects of midazolam on microsomal steroid hydroxylation by measuring basal and ACTH-stimulated cortisol and 17α-hydroxyprogesterone (17-OHP) synthesis. Threshold inhibition of basal cortisol production was achieved by 3·4 μmol midazolam/1 while ACTH-stimulated production required 13·6 μmol/l. This was accompanied by a biphasic response of 17-OHP production, rising to a maximum at 13·6 μmol midazolam/l for basal and 6·8 μmol midazolam/l for ACTH-stimulated synthesis suggesting a preferential inhibitory effect on 21-hydroxylase activity at < 6·8 μmol/l and additonal effects on 17α-hydroxylation at higher drug concentrations. This explains the inhibition of ACTH-stimulated cortisol synthesis by midazolam (50% inhibitor dose (IC50) 22 μmol/l). Using 21-deoxycortisol as substrate, we have demonstrated that midazolam is a competitive inhibitor of 21-hydroxylase (inhibitory constant (KI) 35 μmol/l). Both midazolam and diazepam inhibited K+-stimulated aldosterone synthesis, with IC50 values of 1·2 μmol/l and 0·8 μmol/l respectively, which are far lower than those observed for ACTH-stimulated cortisol synthesis. With 11β-hydroxyprogesterone as substrate, the KI for the inhibition of aldosterone synthesis by midazolam was 54 μmol/l. Potassium stimulates aldosterone biosynthesis at least partly by changing intracellular free calcium levels. To investigate possible antagonistic effects of benzodiazepines on calcium metabolism, we measured 45Ca uptake in the presence of midazolam. Both basal (P < 0·01) and K+-stimulated 45Ca uptake (P < 0·05) were inhibited by the drug although the effects of K+ were not completely abolished. Comparison of the dose-dependent effects of midazolam on basal 45Ca uptake in cell suspensions prepared from different areas of the adrenal cortex indicated that zona glomerulosa cells are more sensitive to midazolam. We confirm that benzodiazepines at low concentrations have a direct effect on microsomal steroid hydroxylase enzymes in vitro and postulate that the greater sensitivity to benzodiazepines of K+-stimulated aldosterone synthesis, when compared with either ACTH-stimulated cortisol synthesis or conversion of 21-deoxycortisol to cortisol, may be explained by additional effects of these drugs on plasma membrane calcium transport. Journal of Endocrinology (1992) 135, 361–369

scholarly journals Obestatin Plays an Opposite Role in the Regulation of Pituitary Somatotrope and Corticotrope Function in Female Primates and Male/Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1407-1417 ◽  
Author(s):  
Raúl M. Luque ◽  
José Córdoba-Chacón ◽  
Alejandro Ibáñez-Costa ◽  
Iacopo Gesmundo ◽  
Cristina Grande ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Somatostatin Receptors ◽  
Inhibitory Effect ◽  
Pituitary Function ◽  
Pituitary Hormone ◽  
Mrna Levels ◽  
Ghrh Receptor ◽  
Acth Release

Obestatin is a 23-amino-acid amidated peptide that is encoded by the ghrelin gene. Previous studies have shown obestatin can modulate the hypothalamic neuronal circuitry that regulates pituitary function, perhaps by modulating the actions of ghrelin. However, the direct actions of obestatin on pituitary function remain controversial. Here, primary pituitary cell cultures from a nonhuman primate (baboon) and mice were used to test the effects of obestatin on pituitary hormone expression and secretion. In pituitary cultures from both species, obestatin had no effect on prolactin, LH, FSH, or TSH expression/release. Conversely, obestatin stimulated proopiomelanocortin expression and ACTH release and inhibited GH expression/release in vitro, actions that were also observed in vivo in mice treated with obestatin. In vitro, obestatin inhibited the stimulatory actions of ghrelin on GH but not ACTH release. The inhibitory effect of obestatin on somatotrope function was associated with an overall reduction in pituitary transcription factor-1 and GHRH receptor mRNA levels in vitro and in vivo as well as a reduction in hypothalamic GHRH and ghrelin expression in vivo. The stimulatory effect of obestatin on ACTH was associated with an increase in pituitary CRF receptors. Obestatin also reduced the expression of pituitary somatostatin receptors (sst1/sst2), which could serve to modify its impact on hormone secretion. The in vitro actions of obestatin on both GH and ACTH release required the adenylyl cyclase and MAPK routes. Taken together, our results provide evidence that obestatin can act directly at the pituitary to control somatotrope and corticotrope function, and these effects are conserved across species.

scholarly journals Long-Term Treatment with Atypical Antipsychotic Iloperidone Modulates Cytochrome P450 2D (CYP2D) Expression and Activity in the Liver and Brain via Different Mechanisms

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3472
Author(s):  
Przemysław J. Danek ◽  
Władysława A. Daniel
Keyword(s):  
Substantia Nigra ◽  
Frontal Cortex ◽  
Inhibitory Effect ◽  
Term Treatment ◽  
Mrna Levels ◽  
Nigrostriatal Pathway ◽  
Long Term Treatment ◽  
The Brain ◽  
Expression And Activity

CYP2D enzymes engage in the synthesis of endogenous neuroactive substances (dopamine, serotonin) and in the metabolism of neurosteroids. The present work investigates the effect of iloperidone on CYP2D enzyme expression and activity in rat brains and livers. Iloperidone exerted a weak direct inhibitory effect on CYP2D activity in vitro in the liver and brain microsomes (Ki = 11.5 μM and Ki = 462 μM, respectively). However, a two-week treatment with iloperidone (1 mg/kg ip.) produced a significant decrease in the activity of liver CYP2D, which correlated positively with the reduced CYP2D1, CYP2D2 and CYP2D4 protein and mRNA levels. Like in the liver, iloperidone reduced CYP2D activity and protein levels in the frontal cortex and cerebellum but enhanced these levels in the nucleus accumbens, striatum and substantia nigra. Chronic iloperidone did not change the brain CYP2D4 mRNA levels, except in the striatum, where they were significantly increased. In conclusion, by affecting CYP2D activity in the brain, iloperidone may modify its pharmacological effect, via influencing the rate of dopamine and serotonin synthesis or the metabolism of neurosteroids. By elevating the CYP2D expression/activity in the substantia nigra and striatum (i.e., in the dopaminergic nigrostriatal pathway), iloperidone may attenuate extrapyramidal symptoms, while by decreasing the CYP2D activity and metabolism of neurosteroiods in the frontal cortex and cerebellum, iloperidone can have beneficial effects in the treatment of schizophrenia. In the liver, pharmacokinetic interactions involving chronic iloperidone and CYP2D substrates are likely to occur.

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