scholarly journals What is molt-inhibiting hormone? The role of an ecdysteroidogenesis inhibitor in the crustacean molting cycle

1989 ◽  
Vol 86 (17) ◽  
pp. 6826-6829 ◽  
Author(s):  
Yoko Naya ◽  
Mayumi Ohnishi ◽  
Midori Ikeda ◽  
Wataru Miki ◽  
Koji Nakanishi
Keyword(s):  
Procambarus Clarkii ◽  
Active Form ◽  
Xanthurenic Acid ◽  
Sinus Gland ◽  
Inhibitory Effects ◽  
Molting Cycle ◽  
Biosynthesis Inhibitors

The in vivo molt-inhibitory effects of the ecdysone biosynthesis inhibitors 3-hydroxy-L-kynurenine and xanthurenic acid were investigated. These ecdysone biosynthesis inhibitors, isolated from the eyestalks of blue crabs (Callinectes sapidus), were injected into eyestalk-ablated crayfish (Procambarus clarkii). The active factor was found to be species-nonspecific within crabs and crayfish. The seasonal profiles of the xanthurenic acid and ecdysone titers exhibited a staggered relationship. Moreover, the activity of a 3-hydroxy-L-kynurenine aminotransferase varied during the molting cycle. The data suggested that 3-hydroxy-L-kynurenine, which is secreted from the X-organ-sinus gland complex of crustaceans, is released into the hemolymph, and after accumulating at the surface of the Y-organ, is converted into the active form, xanthurenic acid. Xanthurenic acid was found to profoundly repress ecdysteroidogenesis in vitro.

Abstract 13598: The G-protein BetaGamma Subunits Regulate Platelet Function

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ahmed Alarabi ◽  
Zubair Karim ◽  
Victoria Hinojos ◽  
Patricia A Lozano ◽  
Keziah Hernandez ◽  
...  
Keyword(s):  
G Protein ◽  
Platelet Function ◽  
Thrombus Formation ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Clot Retraction ◽  
Betagamma Subunits

Platelet activation involves tightly regulated processes to ensure a proper hemostasis response, but when unbalanced, can lead to pathological consequences such as thrombus formation. G-protein coupled receptors (GPCRs) regulate platelet function by interacting with and mediating the response to various physiological agonists. To this end, an essential mediator of GPCR signaling is the G protein Gαβγ heterotrimers, in which the βγ subunits are central players in downstream signaling pathways. While much is known regarding the role of the Gα subunit in platelet function, that of the βγ remains poorly understood. Therefore, we investigated the role of Gβγ subunits in platelet function using a Gβγ (small molecule) inhibitor, namely gallein. We observed that gallein inhibits platelet aggregation and secretion in response to agonist stimulation, in both mouse and human platelets. Furthermore, gallein also exerted inhibitory effects on integrin αIIbβ3 activation and clot retraction. Finally, gallein’s inhibitory effects manifested in vivo , as documented by its ability to modulate physiological hemostasis and delay thrombus formation. Taken together, our findings demonstrate, for the first time, that Gβγ directly regulates GPCR-dependent platelet function, in vitro and in vivo . Moreover, these data highlight Gβγ as a novel therapeutic target for managing thrombotic disorders.

CNS Myelin: Does a Stabilizing Role in Neurodevelopment Result in Inhibition of Neuronal Repair after Adult Injury?

1998 ◽  
Vol 4 (4) ◽  
pp. 273-284 ◽  
Author(s):  
H. S. Keirstead ◽  
John D. Steeves
Keyword(s):  
Neural Development ◽  
Neurite Growth ◽  
In Vivo Studies ◽  
Inhibitory Effects ◽  
Axonal Plasticity ◽  
Collateral Sprouting ◽  
Axonal Connections

The inhibitory properties of mature oligodendrocytes and CNS myelin for neurite outgrowth were clearly documented more than a decade ago in studies involving co-cultures of dissociated glial cells and neurons. Since then, in vitro and in vivo studies have begun to characterize some of the CNS myelin-associated inhibitors of neurite growth. Furthermore, experimental techniques for neutralizing or suppressing these inhibitory effects have been developed. The results of several experiments, involving the suppression of myelination in the developing or adult CNS, suggest that the relatively late appearance of CNS myelin during neural development may serve to stabilize and restrict axonal outgrowth (e.g., collateral sprouting) after appropriate axonal connections have been established. This suggested developmental role of myelin may consolidate and limit the degree of axonal plasticity within the adult CNS; consequently, however, it might also limit axonal regeneration after injury.

scholarly journals Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chengjie Lian ◽  
Tianyu Tao ◽  
Peiqiang Su ◽  
Zhiheng Liao ◽  
Xudong Wang ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Transcriptional Level ◽  
Inhibitory Effects ◽  
Osteoarthritis Progression ◽  
Anticytokine Therapy ◽  
Potential Strategy ◽  
Underlying Inflammation

Abstract Inflammation participates in the development of OA and targeting inflammatory signaling pathways is a potential strategy for OA treatment. IL-1β is one of the most important inflammatory factors to trigger the activation of NF-κB signaling and accelerate OA progression, whereas OA patients could hardly benefit from inhibiting IL-1β in clinic, suggesting the importance to further explore the details of OA inflammation. We here showed that expression of miR-18a in chondrocytes was specifically induced in response to IL-1β in vitro as well as in rat model of OA during which NF-κB signaling was involved, and that nuclear-translocated p65 directly upregulated miR-18a expression at transcriptional level. Further, increased miR-18a mediated hypertrophy of chondrocytes, resulting in OA degeneration, by targeting TGFβ1, SMAD2, and SMAD3 and subsequently leading to repression of TGF-β signaling. And the level of serum miR-18a was positively correlated to severity of OA. Interestingly, other than IL-1β, pro-inflammation cytokines involving TNFα could also remarkably upregulate miR-18a via activating NF-κB signaling and subsequently induce chondrocytes hypertrophy, suggesting a pivotal central role of miR-18a in inflammatory OA progression. Thus, our study revealed a novel convergence of NF-κB and TGF-β signaling mediated by miR-18a, and a novel mechanism underlying inflammation-regulated OA dependent of NF-κB/miR-18a/TGF-β axis. Notably, in vivo assay showed that targeting miR-18a sensitized OA chondrocytes to IL-1β inhibitor as targeting IL-1β and miR-18a simultaneously had much stronger inhibitory effects on OA progression than suppressing IL-1β alone. Therefore, the diagnostic and therapeutic potentials of miR-18a for OA were also revealed.

Salmon calcitonin inhibits whole body Ca2+ uptake in young rainbow trout

1997 ◽  
Vol 155 (3) ◽  
pp. 459-465 ◽  
Author(s):  
GF Wagner ◽  
EM Jaworski ◽  
DP Radman
Keyword(s):  
Rainbow Trout ◽  
Transport Process ◽  
Plasma Calcium ◽  
Whole Body ◽  
Mrna Levels ◽  
Inhibitory Effects ◽  
Negative Regulators

Gill Ca2+ transport (GCAT) in fish is regulated by a number of different hormones. Stanniocalcin (STC) from the corpuscles of Stannius (CS) is an inhibitor of GCAT, whereas pituitary-derived prolactin and cortisol stimulate GCAT. Other than this, however, little is known about the effects of other hormones on this important transport process. The role of calcitonin (CT) in calcium homeostasis in fish is still controversial. Whereas many studies have shown significant effects of CT on plasma calcium levels, an equal number of studies have failed to find any correlations between plasma calcium and CT levels in fish. Previous in vitro studies have shown that salmon CT has potent inhibitory effects on GCAT in isolated, perfused fish gill preparations, a finding that has never been corroborated in vivo. Therefore, in this report we examined the effects of salmon CT on whole body 45Ca uptake (as a measure of GCAT) in young rainbow trout. In support of the in vitro findings, we found that CT had significant inhibitory effects on GCAT. In parallel studies, we found that CT had no effects on STC secretion and only modest, stimulatory effects on STC mRNA levels in cultured trout CS cells. These finding suggest that both CT and STC function as negative regulators of GCAT in fish.

scholarly journals Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yingfeng Tu ◽  
Li Liu ◽  
Dongliang Zhao ◽  
Youbin Liu ◽  
Xiaowei Ma ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Tumor Model ◽  
Drug Candidate ◽  
Signal Pathways ◽  
Inhibitory Effects ◽  
Proliferation And Apoptosis ◽  
Tumor Growth And Metastasis

Abstract Recent studies reported miR-497 exhibited inhibitory effects in various cancers. However, whether miR-497 is involved in inhibiting angiogenesis, which is critical for tumor growth and metastasis, is still unknown. The purpose of this study was to investigate the potential role of miR-497 in tumor angiogenesis. In this work, cell proliferation and apoptosis analyses were conducted to explore the potential function of miR-497 in HUVECs by using MTT and TUNEL assays. Western blotting (WB) was employed to validate the downstream targets of miR-497. Furthermore, in order to disclose the role of miR-497 on angiogenesis, VEGFR2-luc transgenic mice were treated with miR-497 mimic and applied to monitor tumor angiogenesis and growth by in vivo bioluminescent imaging (BLI). The results demonstrated that overexpression of miR-497 showed inhibitory effects on VEGFR2 activation and downstream Raf/MEK/ERK signal pathways in vitro and in vivo. Moreover, overexpression of miR-497 effectively induced HUVECs apoptosis by targeting VEGFR2 and downstream PI3K/AKT signaling pathway. Furthermore, miR-497 exhibited anti-angiogenesis and anti-tumor effects in the VEGFR2-luc breast tumor model proven by BLI, WB and immunohistochemistry analysis. In summary, miR-497 inhibits tumor angiogenesis and growth via targeting VEGFR2, indicating miR-497 can be explored as a potential drug candidate for cancer therapy.

scholarly journals Active role of free RNA during the early phase of proteostasis stress

2019 ◽  
Author(s):  
Marion Alriquet ◽  
Adrían Martínez-Limón ◽  
Gerd Hanspach ◽  
Martin Hengesbach ◽  
Gian G. Tartaglia ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Active Form ◽  
Active Role ◽  
Structural Features ◽  
Cellular Functions ◽  
Granule Formation

ABSTRACTTransient sequestration of proteins and RNA is an essential principle of cellular reaction to stress. Compared to polypeptides, less is known about the role of RNA released from polysomes during acute proteostasis stress. Using quantitative mass spectrometry, we identified a set of proteins assembled by free RNA in the heat-shocked mammalian cytosol. RNA-associated proteins displayed higher disorder and larger size, which supports the role of multivalent interactions during the initial phase of the RNA granule formation. Structural features of the free RNA interactors defined them as a subset of RNA-binding proteins. The interactome contained preferentially the active form of eIF2α. The interaction between assembled proteins in vivo required RNA. The reconstitution of the association process in vitro indicated to the multimolecular basis for the increased binding to RNA upon heat shock in the cytosol. Our results reveal how free RNA can participate in reorganization of cellular functions during proteostasis stress.

scholarly journals Role of Vitamin D on the Inhibition of Gastrin Production After Cisplatin Treatment

2000 ◽  
Vol 7 (3) ◽  
pp. 115-119 ◽  
Author(s):  
Ying Wang ◽  
Surinder K. Aggarwal ◽  
Will Kopachik
Keyword(s):  
Vitamin D ◽  
Active Form ◽  
Treatment Groups ◽  
Calcium Supplements ◽  
Blot Technique ◽  
Before And After ◽  
Male Wistar Rats

In rats cisplatin induces hypocalcemia, bloating of the stomach, and ulceration ameliorated through calcium supplements. This study was undertaken to test the role of calcium on the gastrin mRNA production in vitro and in vivo. RIN B6 cells were cultured in medium with calcium (1.8, 3.6 and 7.2 mM) and the active form of vitamin D (calcijex). Cisplatin was added (10 μg/ml) for 12 hrs and cells were harvested for RNA from various treatment groups. Male Wistar rats were treated with cisplatin (9 mg/kg), before and after vitamin D (0.3 mg/100g/week). The rats were killed and stomach tissues excised on 1, 6, 10 and 15 days after cisplatin treatment. RNA from the stomach was analyzed using the northern blot technique. Gastrin mRNA was suppressed after cisplatin treatment both in vitro and in vivo. In vitro calcium but not vitamin D additions partially prevented the gastrin mRNA. In vivo, however, vitamin D and calcium were equally effective in preventing gastrin mRNA loss.

scholarly journals Dicer-dependent production of microRNA221 in hepatocytes inhibits p27 and is required for liver regeneration in mice

2017 ◽  
Vol 312 (5) ◽  
pp. G464-G473 ◽  
Author(s):  
Yuki Oya ◽  
Ryota Masuzaki ◽  
Daisuke Tsugawa ◽  
Kevin C. Ray ◽  
Yongchao Dou ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Hepatocyte Proliferation ◽  
Inhibitory Effects ◽  
Primary Hepatocytes ◽  
Direct Role ◽  
Targeted Inhibition ◽  
Dependent Mechanism

Dicer processes microRNAs (miRs) into active forms in a wide variety of tissues, including the liver. To determine the role of Dicer in liver regeneration, we performed a series of in vivo and in vitro studies in a murine 2/3 hepatectomy model. Dicer was downregulated after 2/3 hepatectomy, and loss of Dicer inhibited liver regeneration associated with decreased cyclin A2 and miR-221, as well as increased levels of the cell cycle inhibitor p27. In vitro, miR-221 inhibited p27 production in primary hepatocytes and increased hepatocyte proliferation. Specific reconstitution of miR-221 in hepatocyte-specific Dicer-null mice inhibited p27 and restored liver regeneration. In wild type mice, targeted inhibition of miR-221 using a cholesterol-conjugated miR-221 inhibited hepatocyte proliferation after 2/3 hepatectomy. These results identify Dicer production of miR-221 as an essential component of a miRNA-dependent mechanism for suppression of p27 that controls the rate of hepatocyte proliferation after partial hepatectomy. NEW & NOTEWORTHY Our findings demonstrate a direct role for microRNAs in controlling the rate of liver regeneration after injury. By deleting Dicer, an enzyme responsible for processing microRNAs into mature forms, we determined miR-221 is a critical microRNA in the physiological process of restoration of liver mass after injury. miR-221 suppresses p27, releasing its inhibitory effects on hepatocyte proliferation. Pharmaceuticals based on miR-221 may be useful to modulate hepatocyte proliferation in the setting of liver injury.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Sign in / Sign up

Export Citation Format

Share Document