Differential Regulation of Prostaglandin Production Mediated by Corticotropin-Releasing Hormone Receptor Type 1 and Type 2 in Cultured Human Placental Trophoblasts

Prostaglandin (PG) production by intrauterine tissues plays a key part in the control of pregnancy and parturition. The present study was to investigate the role of placenta-derived CRH and CRH-related peptides in the regulation of PG synthesis and metabolism. We found that placental trophoblasts expressed both CRH-R1 and CRH-R2. Treatment of cultured placental cells with either a CRH or urocortin I (UCNI) antibody resulted in a significant decrease in PGE2 release. Both CRH and UCNI antibodies significantly decreased mRNA and protein expression of synthetic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2 and increased mRNA and protein expression of 15-hydroxyprostaglandin dehydrogenase (PGDH), the key enzyme of PG metabolism. CRH-R1/-R2 antagonist astressin and CRH-R1 antagonist antalarmin significantly inhibited PGE2 release, whereas CRH-R2 antagonist astressin-2b had no effect on PGE2 release. Administration of astressin decreased expression of cPLA2 but had no effect on COX-2 expression. Antalarmin reduced cPLA2 and COX-2 expression, whereas astressin-2b did not alter cPLA2 expression but increased COX-2 expression. PGDH expression was enhanced by these three antagonists. Cells treated with exogenous CRH and UCNI showed an increase in PGE2 release and expression of cPLA2 and COX-2 but a decrease in PGDH expression. UCNII and UCNIII had no effect on PGE2 release but decreased COX-2 and PGDH expression. Our results suggested CRH and CRH-related peptides act on CRH-R1 and CRH-R2 to exert different effects on PG biosynthetic enzymes cPLA2 and COX-2 and thereby modulate output of PGs from placenta, which would be important for controlling pregnancy and parturition.

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Apurinic/apyrimidinic endonuclease-1 is associated with angiogenesis and VEGF production via upregulation of COX-2 expression in esophageal cancer tissues

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00057.2013 ◽

2014 ◽

Vol 306 (3) ◽

pp. G183-G190 ◽

Cited By ~ 11

Author(s):

Hiroyuki Nagoya ◽

Seiji Futagami ◽

Mayumi Shimpuku ◽

Atsushi Tatsuguchi ◽

Taiga Wakabayashi ◽

...

Keyword(s):

Esophageal Cancer ◽

Protein Expression ◽

Cell Lines ◽

Excision Repair ◽

Multifunctional Protein ◽

Expression Levels ◽

Key Enzyme ◽

Mrna And Protein Expression ◽

Cox 2 ◽

Cancer Tissues

Apurinic/apyrimidinic endonuclease-1 (APE-1) is a key enzyme responsible for DNA base excision repair and is also a multifunctional protein such as redox effector for several transcriptional factors. Our study was designed to investigate APE-1 expression and to study its interaction with cyclooxygenase (COX)-2 expression and VEGF production in the esophageal cancer. The expression of APE-1, COX-2, monocyte chemoattractant protein (MCP)-1, CC-chemokine receptor (CCR)2, and VEGF were evaluated by immunohistochemistry in 65 human esophageal squamous cell carcinoma (ESCC) tissues. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of APE-1 and p-signal transducer and activator of transcription 3 (STAT3) expression in MCP-1-stimulated ESCC cell lines (KYSE 220 and EC-GI-10). siRNA for APE-1 was treated to determine the role of APE-1 in the regulation of COX-2 expression, VEGF production, and antiapoptotic effect against cisplatin. In human ESCC tissues, nuclear localization of APE-1 was observed in 92.3% (60/65) of all tissues. There was a significant relationship ( P = 0.029, R = 0.49) between nuclear APE-1 and cytoplasmic COX-2 expression levels in the esophageal cancer tissues. In KYSE 220 and EC-GI-10 cells, MCP-1 stimulation significantly increased mRNA and protein expression of APE-1. Treatment with siRNA for APE-1 significantly inhibited p-STAT3 expression levels in MCP-1-stimulated cells. Furthermore, treatment of siRNA for APE-1 significantly reduced COX-2 expression and VEGF production in MCP-1-stimulated esophageal cancer cell lines. Treatment with APE-1 siRNA significantly increased apoptotic levels in cisplatin-incubated KYSE 220 and EC-GI-10 cells. We concluded that APE-1 is overexpressed and associated with COX-2 expression and VEGF production in esophageal cancer tissues.

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Regulatory Role of Heat Shock Proteins in the Pathogenesis of Type 1 and Type 2 Diabetes

Current Immunology Reviews ◽

10.2174/1573395513666170606121625 ◽

2017 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Christiane Habich ◽

Henrike Sell ◽

Volker Burkart

Keyword(s):

Type 2 Diabetes ◽

Heat Shock ◽

Heat Shock Proteins ◽

Regulatory Role ◽

Shock Proteins

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Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

International Journal of Molecular Sciences ◽

10.3390/ijms22084020 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4020

Author(s):

Enrique Antonio Alfonso-Muñoz ◽

Raquel Burggraaf-Sánchez de las Matas ◽

Jorge Mataix Boronat ◽

Julio César Molina Martín ◽

Carmen Desco

Keyword(s):

Diabetic Retinopathy ◽

Diabetic Macular Oedema ◽

Complementary Therapy ◽

Antioxidant Supplementation ◽

Current Management ◽

Adult Type ◽

Aged People

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

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EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

Pulmonary Circulation ◽

10.1177/20458940211029550 ◽

2021 ◽

pp. 204589402110295

Author(s):

Hirohisa Taniguchi ◽

Tomoya Takashima ◽

Ly Tu ◽

RaphaÃ«l Thuillet ◽

Asuka Furukawa ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Neurofibromatosis Type ◽

Pulmonary Vascular Remodeling ◽

Life Threatening ◽

History Of ◽

Pulmonary Arterial ◽

First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

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Abstract P059: A A Role of Aminopeptidase A in the Brain on Cardiovascular Regulation of Conscious Rat

Hypertension ◽

10.1161/hyp.66.suppl_1.p059 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Takuto Nakamura ◽

Masanobu Yamazato ◽

Akio Ishida ◽

Yusuke Ohya

Keyword(s):

Blood Pressure ◽

Protein Expression ◽

Drinking Behavior ◽

Cardiovascular Regulation ◽

Ang Ii ◽

Hypertensive Rats ◽

Aminopeptidase A ◽

The Brain

Objective: Aminopeptidase A (APA) have important role in conversion of Ang II to Ang III. Intravenous APA administration lowers blood pressure in hypertensive rats. In contrast, APA inhibition in the brain lowers blood pressure in hypertensive rats. Therefore APA might have different role on cardiovascular regulation. However, a role of APA and Ang III on cardiovascular regulation especially in the brain has not been fully understood. Our purpose of present study was to investigate a role of APA and Ang III in the brain on cardiovascular regulation in conscious state. Method: 12-13 weeks old Wistar Kyoto rat (WKY) and 12-16 weeks old spontaneously hypertensive rat (SHR) were used. i) APA distribution in the brain was evaluated by immunohistochemistry. Protein expression of APA was evaluated by Western blotting. Enzymatic activity of APA was evaluated using L-glutamic acid γ-(4-nitroanilide) as a substrate. ii) WKY received icv administration of Ang II 25ng/2μL and Ang III 25ng/2μL. We recorded change in mean arterial pressure (MAP) in conscious and unrestraied state and measured induced drinking time. iii) SHR received icv administeration of recombinant APA 400ng/4μL. We recorded change in MAP in conscious and unrestraied state and measured induced drinking time. Result: i) APA was diffusely immunostained in the cells of brain stem including cardiovascular regulatory area such as rostral ventrolateral medulla. Protein expression and APA activity in the brain were similar between WKY (n=3) and SHR (n=3).ii) Icv administration of Ang II increased MAP by 33.8±3.8 mmHg and induced drinking behavior for 405±90 seconds (n=4). Icv administration of Ang III also increased MAP by 24.7±2.4 mmHg and induced drinking behavior for 258±62 seconds (n=3). These vasopressor activity and induced drinking behavior was completely blocked by pretretment of angiotensin receptor type 1 blocker.iii) Icv administration of APA increased MAP by 10.0±1.7 mmHg (n=3). Conclusion: These results suggested that Ang III in the brain increase blood pressure by Angiotensin type 1 receptor dependent mechanism and APA in the brain may involved in blood pressure regulation as a vasopressor enzyme.

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The role of modifiable pre-pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340903176859 ◽

2009 ◽

Vol 88 (10) ◽

pp. 1153-1157 ◽

Cited By ~ 11

Author(s):

Melanie E. Inkster ◽

Tom P. Fahey ◽

Peter T. Donnan ◽

Graham P. Leese ◽

Gary J. Mires ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Fetal Outcomes ◽

Pregnancy Risk

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Keratoprostheses in silicone oil-filled eyes: long-term outcomes

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-312426 ◽

2018 ◽

Vol 103 (6) ◽

pp. 781-788 ◽

Cited By ~ 2

Author(s):

Geetha Iyer ◽

Bhaskar Srinivasan ◽

Shweta Agarwal ◽

Ruchika Pattanaik ◽

Ekta Rishi ◽

...

Keyword(s):

Silicone Oil ◽

Vitreoretinal Surgery ◽

Retrospective Chart Review ◽

Protective Role ◽

Visual Rehabilitation ◽

Two Factors

PurposeTo analyse the functional and anatomical outcomes of different types of keratoprostheses in eyes with retained silicone oil following vitreoretinal surgery.MethodsRetrospective chart review of patients operated with any type of permanent keratoprosthesis (Kpro) in silicone oil-filled eyes between March 2003 and June 2017 were analysed.Results40 silicone oil-filled eyes underwent keratoprostheses, of which 22 were type 1 and 18 were type 2 Kpros (Lucia variant—nine, modified osteo odonto kerato prosthesis (MOOKP)—four, Boston type 2—three and osteoKpro—two) with a mean follow-up of 61.54 , 42.77, 45.25 , 25 and 37 months, respectively. Anatomic retention of the primary Kpro was noted in 33 eyes (82.5%). A best-corrected visual acuity of better than 20/200 and 20/400 was achieved in 26 (65%)+32 (80%) eyes. Retroprosthetic membrane (RPM) was the most common complication noted in 17 eyes (42.5%). Perioptic graft melt was noted in 4 of 22 eyes of the type 1 Kpro (2 (10.5%) without associated ocular surface disorder (OSD)) and in 1 eye each of Boston and Lucia type 2 Kpro. Laminar resorption occurred in one eye each of the MOOKP and OKP groups. Endophthalmitis and glaucoma did not occur in any eye.ConclusionAppropriately chosen keratoprosthesis is a viable option for visual rehabilitation in eyes post vitreoretinal surgery with retained silicone oil-induced keratopathy not amenable to conventional penetrating keratoplasty. Kpro melt among type 1 Kpro did not occur in 89.5% eyes without associated OSD (19 of 22 eyes), despite the lack of aqueous humour and presence of RPM (4 eyes), two factors considered to play a significant role in the causation of sterile melts. Of interest to note was the absence of infection in any of these eyes. The possible protective role of oil from endophthalmitis is interesting, though yet to be ascertained.

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The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

Journal of Education, Health and Sport ◽

10.12775/jehs.2021.11.09.071 ◽

2021 ◽

Vol 11 (9) ◽

pp. 544-549

Author(s):

Paulina Trojanowska ◽

Magdalena Chrościńska-Krawczyk ◽

Alina Trojanowska ◽

Ewa Tywanek ◽

Jakub Wronecki ◽

...

Keyword(s):

Innate Immunity ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

The Body ◽

Low Grade ◽

Intracellular Space ◽

Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

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