Conformational biosensors reveal allosteric interactions between heterodimeric AT1 angiotensin and prostaglandin F2α receptors

SummaryRidogrel (6.3 × 10−6 to 10−4 M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 × 10−6 M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within}D min of incubation of the blood vessel with the compound and easily reversible. Ridogrel antagonised contractions of isolated rabbit femoral arteries caused by prostaglandin Fzo2α in the same concentration range. Ridogrel also inhibited contractions induced by aggregating rat platelets on isolated rat caudal arteries (itt the presence of ketanserin 4 × 10−7 M) and on isolated rabbit pulmonary and femoral arteries (in the absence of ketanserin). Ridogrel had no effect on Ca2+-induced contractions in depolarised isolated rabbit femoral arteries, and at 10−4 M antagonised serotonin-induced contractions in this blood vessel. Its effect on serotonin-induced contractions was statistically significant but very small on isolated rat caudal arteries. These observations indicate that ridogrel is an antagonist of prostaglandin endoperoxide/thromboxane A2 and prostaglandin F2α raCeptors on vascular smooth muscle.

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THE EFFECT OF PROSTAGLANDIN-F2α ON THE CONVERSION OF PREGNENOLONE TO PROGESTERONE BY THE AUTOTRANSPLANTED OVARY OF THE EWE

Acta Endocrinologica ◽

10.1530/acta.0.080s047 ◽

1975 ◽

Vol 80 (1_Suppla) ◽

pp. S47 ◽

Cited By ~ 1

Author(s):

H.-O. Hoppen ◽

J. K. Findlay

Keyword(s):

Prostaglandin F2α

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Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults

10.2337/figshare.12076134 ◽

2020 ◽

Author(s):

Bin Wang ◽

Weihong Qiu ◽

Shijie Yang ◽

Limin Cao ◽

Chunmei Zhu ◽

...

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Oxidative Dna Damage ◽

Adult Population ◽

Prostaglandin F2α ◽

Mediation Analyses ◽

Mediating Role ◽

Fasting Plasma

<a>OBJECTIVE: </a>Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation and fasting plasma glucose (FPG) alteration, and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG. RESEARCH DESIGN AND METHODS: FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxy-guanosine, 8-OHdG), lipid peroxidation (8-iso-prostaglandin-F2α, 8-iso-PGF2α) and acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-L-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, GAMA) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. RESULTS: We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG (except GAMA with FPG), and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, ΣUAAM (AAMA+GAMA) or 8-iso-PGF2α was associated with a 0.17-, 0.15- or 0.23-mmol/L increase in FPG, respectively (P or/and P trend<0.05). Each 1% increase in AAMA, GAMA or ΣUAAM was associated with a 0.19%, 0.27% or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48% or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend<0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA and ΣUAAM associated-FPG increases, respectively. CONCLUSIONS: Exposure of general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.

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Recent Progress in Research of Prostaglandin F2α Production in Domestic Animals

Nihon Chikusan Gakkaiho ◽

10.2508/chikusan.59.107 ◽

1988 ◽

Vol 59 (2) ◽

pp. 107-116

Author(s):

Tatsuo NAKAHARA

Keyword(s):

Recent Progress ◽

Prostaglandin F2α ◽

Domestic Animals

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HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02209-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Gen Kuroyanagi ◽

Go Sakai ◽

Takanobu Otsuka ◽

Naohiro Yamamoto ◽

Kazuhiko Fujita ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Map Kinase ◽

Interleukin 6 ◽

Prostaglandin F2α ◽

P38 Map Kinase ◽

Vascular Endothelial ◽

Mitogen Activated Protein ◽

Endothelial Growth Factor ◽

Vegf Release

Abstract Background Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells. Methods MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting. Results The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation. Conclusions Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.

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Characterization of an Ex Vivo Equine Endometrial Tissue Culture Model Using Next-Generation RNA-Sequencing Technology

Animals ◽

10.3390/ani11071995 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1995

Author(s):

Maithê R. Monteiro de Barros ◽

Mina C. G. Davies-Morel ◽

Luis A. J. Mur ◽

Christopher J. Creevey ◽

Roger H. Alison ◽

...

Keyword(s):

Tissue Culture ◽

Ex Vivo ◽

Prostaglandin F2α ◽

Principal Component ◽

Differentially Expressed ◽

Temporal Window ◽

Cellular Processes ◽

Persistent Inflammation ◽

Uterine Inflammation ◽

Tissue Culture Model

Persistent mating-induced endometritis is a major cause of poor fertility rates in the mare. Endometritis can be investigated using an ex vivo equine endometrial explant system which measures uterine inflammation using prostaglandin F2α as a biomarker. However, this model has yet to undergo a wide-ranging assessment through transcriptomics. In this study, we assessed the transcriptomes of cultured endometrial explants and the optimal temporal window for their use. Endometrium harvested immediately post-mortem from native pony mares (n = 8) were sampled (0 h) and tissue explants were cultured for 24, 48 and 72 h. Tissues were stored in RNALater, total RNA was extracted and sequenced. Differentially expressed genes (DEGs) were defined using DESeq2 (R/Bioconductor). Principal component analysis indicated that the greatest changes in expression occurred in the first 24 h of culture when compared to autologous biopsies at 0 h. Fewer DEGs were seen between 24 and 48 h of culture suggesting the system was more stable than during the first 24 h. No genes were differentially expressed between 48 and 72 h but the low number of background gene expression suggested that explant viability was compromised after 48 h. ESR1, MMP9, PTGS2, PMAIP1, TNF, GADD45B and SELE genes were used as biomarkers of endometrial function, cell death and inflammation across tissue culture timepoints. STRING assessments of gene ontology suggested that DEGs between 24 and 48 h were linked to inflammation, immune system, cellular processes, environmental information processing and signal transduction, with an upregulation of most biomarker genes at 24 h. Taken together our observations indicated that 24–48 h is the optimal temporal window when the explant model can be used, as explants restore microcirculation, perform wound healing and tackle inflammation during this period. This key observation will facilitate the appropriate use of this as a model for further research into the equine endometrium and potentially the progression of mating-induced endometritis to persistent inflammation between 24 and 48 h.

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