121. EXTRACELLULAR ROLES FOR PROREGIONS OF MOUSE BMP15 AND GDF9 IN VIVO

2009 ◽  
Vol 21 (9) ◽  
pp. 40
Author(s):  
C. J. McIntosh ◽  
S. Lawrence ◽  
J. Juengel ◽  
K. McNatty
Keyword(s):  
Mammalian Species ◽  
Follicular Development ◽  
Biologically Active ◽  
Corpora Lutea ◽  
Mature Protein ◽  
Extracellular Secretion ◽  
Morphogenetic Protein ◽  
Signal Region

Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are essential for normal follicular development and ovulation in mammalian species. As TGF-beta family proteins, BMP15 and GDF9 are expressed as pre-pro-mature proteins, with a signal region prompting extracellular secretion, a proregion that is post-translationally cleaved, and a mature protein that is known to be biologically active as a non-covalently interacting dimer. Until recently, the proregion was thought primarily to facilitate correct folding and dimerization of the mature proteins within the oocyte prior to processing and cleavage. However, our in vitro work with recombinant mouse BMP15 and GDF9 has shown that each of the proregion, mature protein and the non-processed promature protein are secreted from transfected 293H cells. We showed non-covalent interactions existing between the proregion and mature protein of each of BMP15 and GDF9, and between the BMP15 proregion and GDF9 mature protein. Importantly, a mouse BMP15 proregion antibody was able to abolish cooperative BMP15 and GDF9 bioactivity measured using a granulosa cell thymidine incorporation bioassay, providing strong evidence for an extracellular role for the mouse BMP15 proregion. Currently, to find out whether BMP15 and GDF9 proregions have extracellular roles in vivo, our investigation has utilised knock-down of BMP15 and GDF9 proregion proteins by mouse immunisation. Ovaries of mice immunised with the GDF9 proregion had significantly increased numbers of corpora lutea (p<0.005), while ovaries from mice immunised with BMP15 proregion peptides had significantly fewer corpora lutea (p<0.005). These findings provide the first evidence that the proregions of mouse GDF9 and BMP15 have different physiological roles outside the oocyte. Our future aim is to elucidate the function of these proregions, how these may differ between BMP15 and GDF9, and whether these aspects differ between species with different ovulation quota.

ALTERATIONS IN GRANULOSA CELL AROMATASE ACTIVITY ACCOMPANYING PREOVULATORY FOLLICULAR DEVELOPMENT IN THE RAT OVARY WITH EVIDENCE THAT 5α-REDUCED C19 STEROIDS INHIBIT THE AROMATASE REACTION IN VITRO

1980 ◽  
Vol 84 (3) ◽  
pp. 409-419 ◽  
Author(s):  
S. G. HILLIER ◽  
AGNES M. J. VAN DEN BOOGAARD ◽  
L. E. REICHERT ◽  
E. V. VAN HALL
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Hormonal Regulation ◽  
Follicular Development ◽  
Biologically Active ◽  
Aromatase Activity ◽  
Adult Rat ◽  
Oestradiol Production

Locally produced androgens and oestrogens are thought to be important factors in the hormonal regulation of follicular development. In the present study the relationship between follicular maturity and granulosa cell aromatase activity has been examined in vitro. Granulosa cells harvested from the largest antral follicles in adult rat ovaries produced negligible amounts of immunoreactive oestradiol when incubated for 3 h in vitro irrespective of the day of the oestrous cycle upon which they were obtained. However, the addition of aromatizable C19 steroid substrate (testosterone, androstenedione or 19-hydroxyandrostenedione) to the incubation medium resulted in time- and concentration-dependent increases in oestradiol production which were related to the level of follicular maturity attained in vivo. By measuring oestradiol production using testosterone (10−7 mol/l) as substrate, the aromatase activity of granulosa cells obtained on the first day of vaginal dioestrus was shown to be only a fraction (less than 5%) of that observed for cells obtained on the morning of pro-oestrus. Cells obtained on the second day of dioestrus displayed an intermediate level of activity which remained approximately five times lower than that of granulosa cells at pro-oestrus. These observations, therefore, establish the induction or activation of granulosa cell aromatase activity as a correlate of normal preovulatory follicular development. However, intrafollicular androgen/oestrogen ratios may also be influenced by quantitative and/or qualitative alterations in the C19 steroidal substrate available for the aromatase reaction. Thus, the naturally occurring non-aromatizable 5α-reduced androgen metabolites, 5α-dihydrotestosterone and 5α-androstanedione, proved to be potent competitive inhibitors of the granulosa cell aromatase reaction in vitro. In this respect each of these biologically active androgens was more effective than 1-enetestololactone, an established C19 steroidal aromatase inhibitor. Since C19 steroid 5α-reductase is known to be an ovarian enzyme, it is suggested that by affecting the androgenic/oestrogenic composition of the hormonal milieu, local alterations in the activity of this enzyme may be an additional determinant of preovulatory follicular development and function.

scholarly journals Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus)

2009 ◽  
Vol 201 (3) ◽  
pp. 407-418 ◽  
Author(s):  
Shuisheng Li ◽  
Yong Zhang ◽  
Yun Liu ◽  
Xigui Huang ◽  
Weiren Huang ◽  
...  
Keyword(s):  
Optic Tectum ◽  
Carassius Auratus ◽  
Mammalian Species ◽  
Intraperitoneal Administration ◽  
Brain Regions ◽  
Biologically Active ◽  
Pcr Analysis ◽  
Pituitary Cells

To ascertain the neuroendocrine function of the kisspeptin/GPR54 system in non-mammalian species, full-length cDNAs encoding for Kiss1 and Kiss2 as well as their putative cognate receptors GPR54a and GPR54b, were isolated from goldfish (Carassius auratus). The deduced protein sequences between Kiss1 and Kiss2 in goldfish share very low similarity, but their putative mature peptides (kisspeptin-10) are relatively conserved. RT-PCR analysis demonstrated that the goldfish kiss1 gene (gfkiss1) is highly expressed in the optic tectum-thalamus, intestine, kidney, and testis, while the goldfish kiss2 gene (gfkiss2) is mainly detected in the hypothalamus, telencephalon, optic tectum thalamus, adipose tissue, kidney, heart, and gonads. The two receptor genes (gfgpr54a and gfgpr54b) are highly expressed in the brain regions including telencephalon, optic tectum thalamus, and hypothalamus. Both mature goldfish kisspeptin-10 peptides (gfKiss1–10 and gfKiss2–10) are biologically active as they could functionally interact with the two goldfish receptors expressed in cultured eukaryotic cells to trigger the downstream signaling pathways with different potencies. The actions of gfKiss1–10 and gfKiss2–10 on LH secretion were further investigated in vitro and in vivo. Intraperitoneal administration of gfKiss1–10 to sexually mature female goldfish could increase the serum LH levels. However, this peptide does not significantly influence LH release from goldfish pituitary cells in primary culture, indicating that the peptide does not exert its actions at the pituitary level. On the other hand, gfKiss2–10 appears to be a much less potent peptide as it exhibits no significant in vivo bioactivity and is also inactive on the primary pituitary cells.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 270-277 ◽  
Author(s):  
Vijay Kumar ◽  
Simranjeet Singh ◽  
Ragini Bhadouria ◽  
Ravindra Singh ◽  
Om Prakash
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Biologically Active ◽  
Toxicological Studies ◽  
Wide Range ◽  
Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

scholarly journals Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengchuan Zhang ◽  
Ruogu Xu ◽  
Yang Yang ◽  
Chaoan Liang ◽  
Xiaolin Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Titanium Implants ◽  
Extracellular Secretion ◽  
Exosome Biogenesis ◽  
Marrow Mesenchymal Stem Cells ◽  
Proliferation In Vitro ◽  
Extracellular Environment

Abstract Background Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo. Results We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation. Conclusions These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.

scholarly journals Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth of Blastomyces dermatitidis Yeast Form In Vitro

2003 ◽  
Vol 71 (11) ◽  
pp. 6648-6652 ◽  
Author(s):  
Steven Giles ◽  
Charles Czuprynski
Keyword(s):  
Molecular Weight ◽  
Inhibitory Activity ◽  
Mammalian Species ◽  
Blastomyces Dermatitidis ◽  
Low Molecular Weight ◽  
Rat Serum ◽  
Yeast Form ◽  
Domain Iii

ABSTRACT In this study we found that serum inhibitory activity against Blastomyces dermatitidis was principally mediated by albumin. This was confirmed in experiments using albumin from several mammalian species. Analbuminemic rat serum did not inhibit B. dermatitidis growth in vivo; however, the addition of albumin restored inhibitory activity. Inhibitory activity does not require albumin domain III and appears to involve binding of a low-molecular-weight yeast-derived growth factor.

scholarly journals The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Growth Promotion ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Therapeutic Molecules ◽  
Positive Effect

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint

Cartilage ◽  
2020 ◽  
pp. 194760352098015
Author(s):  
Mara H. O’Brien ◽  
Eliane H. Dutra ◽  
Shivam Mehta ◽  
Po-Jung Chen ◽  
Sumit Yadav
Keyword(s):  
Age Groups ◽  
Mandibular Condyle ◽  
Bone Morphogenetic Protein 2 ◽  
Matrix Synthesis ◽  
Cartilage Growth ◽  
Chondrocyte Proliferation ◽  
Conditional Deletion ◽  
Morphogenetic Protein

Objective Bone morphogenetic protein 2 (BMP2) plays important roles in cartilage growth and development. Paradoxically, elevated levels of BMP2 leads to hypertrophic differentiation and osteoarthritis of cartilage. We examined the in vivo loss of BMP2 in cells expressing aggrecan of the mandibular condyle and knee. Design Three-week-old BMP2 flox/flox- CreER-positive mice and their Cre-negative littermates were treated with tamoxifen and raised until 3 or 6 months. We also investigated the direct effects of BMP2 on chondrocytes in vitro. Cells from the mandibular condyle of mice were treated with recombinant human BMP2 (rhBMP2) or rhNoggin (inhibitor of BMP2 signaling). Results Conditional deletion of BMP2 caused breakage of the cartilage integrity in the mandibular condyle of mice from both age groups, accompanied by a decrease in cartilage thickness, matrix synthesis, mineralization, chondrocyte proliferation, and increased expression of degeneration markers, while the effects at articular cartilage were not significant. In vitro results revealed that rhBMP2 increased chondrocyte proliferation, mineralization, and differentiation, while noggin induced opposite effects. Conclusions In conclusion, BMP2 is essential for postnatal maintenance of the osteochondral tissues of the mandibular condyle.

scholarly journals Plant Extracts and Reactive Oxygen Species as Two Counteracting Agents with Anti- and Pro-Obesity Properties

2019 ◽  
Vol 20 (18) ◽  
pp. 4556 ◽  
Author(s):  
Hanna Zielinska-Blizniewska ◽  
Przemyslaw Sitarek ◽  
Anna Merecz-Sadowska ◽  
Katarzyna Malinowska ◽  
Karolina Zajdel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Plant Extracts ◽  
Complex Disease ◽  
Reactive Oxygen ◽  
Complementary Therapy ◽  
Biologically Active ◽  
Mitochondrial Activity ◽  
Oxygen Species

Obesity is a complex disease of great public health significance worldwide: It entails several complications including diabetes mellitus type 2, cardiovascular dysfunction and hypertension, and its prevalence is increasing around the world. The pathogenesis of obesity is closely related to reactive oxygen species. The role of reactive oxygen species as regulatory factors in mitochondrial activity in obese subjects, molecules taking part in inflammation processes linked to excessive size and number of adipocytes, and as agents governing the energy balance in hypothalamus neurons has been examined. Phytotherapy is the traditional form of treating health problems using plant-derived medications. Some plant extracts are known to act as anti-obesity agents and have been screened in in vitro models based on the inhibition of lipid accumulation in 3T3-L1 cells and activity of pancreatic lipase methods and in in vivo high-fat diet-induced obesity rat/mouse models and human models. Plant products may be a good natural alternative for weight management and a source of numerous biologically-active chemicals, including antioxidant polyphenols that can counteract the oxidative stress associated with obesity. This review presents polyphenols as natural complementary therapy, and a good nutritional strategy, for treating obesity without serious side effects.

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