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991.
Jess Liu Drew Czernick Shih-Chun Lin Abeer Alasmari Dibart Serge Erdjan Salih 《Developmental biology》2013
Egg yolk phosvitin is one of the most highly phosphorylated extracellular matrix proteins known in nature with unique physico-chemical properties deemed to be critical during ex-vivo egg embryo development. We have utilized our unique live mouse calvarial bone organ culture models under conditions which dissociates the two bone remodeling stages, viz., resorption by osteoclasts and formation by osteoblasts, to highlight important and to date unknown critical biological functions of egg phosvitin. In our resorption model live bone cultures were grown in the absence of ascorbate and were stimulated by parathyroid hormone (PTH) to undergo rapid osteoclast formation/differentiation with bone resorption. In this resorption model native phosvitin potently inhibited PTH-induced osteoclastic bone resorption with simultaneous new osteoid/bone formation in the absence of ascorbate (vitamin C). These surprising and critical observations were extended using the bone formation model in the absence of ascorbate and in the presence of phosvitin which supported the above results. The results were corroborated by analyses for calcium release or uptake, tartrate-resistant acid phosphatase activity (marker for osteoclasts), alkaline phosphatase activity (marker for osteoblasts), collagen and hydroxyproline composition, and histological and quantitative histomorphometric evaluations. The data revealed that the discovered bioactivity of phosvitin mirrors that of ascorbate during collagen synthesis and the formation of new osteoid/bone. Complementing those studies use of the synthetic collagen peptide analog and cultured calvarial osteoblasts in conjunction with mass spectrometric analysis provided results that augmented the bone organ culture work and confirmed the capacity of phosvitin to stimulate differentiation of osteoblasts, collagen synthesis, hydroxyproline formation, and biomineralization. There are striking implications and interrelationships of this affect that relates to the evolutionary inactivation of the gene of an enzyme l-gulono-γ-lactone oxidase, which is involved in the final step of ascorbate biosynthesis, in many vertebrate species including passeriform birds, reptiles and teleost fish whose egg yolk contain phosvitin. These represent examples of how developing ex-vivo embryos of such species can achieve connective tissue and skeletal system formation in the absence of ascorbate. 相似文献
992.
Jota Oyabu Osamu Yamaguchi Shungo Hikoso Toshihiro Takeda Takafumi Oka Tomokazu Murakawa Hiroki Yasui Hiromichi Ueda Hiroyuki Nakayama Manabu Taneike Shigemiki Omiya Ajay M. Shah Kazuhiko Nishida Kinya Otsu 《Biochemical and biophysical research communications》2013
Cardiac hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Prevention or regression of cardiac hypertrophy can be a major therapeutic target. Although regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified. In the present study, we investigated the role of autophagy in regression of cardiac hypertrophy. Wild-type mice showed cardiac hypertrophy after continuous infusion of angiotensin II for 14 days using osmotic minipumps, and regression of cardiac hypertrophy was observed 7 days after removal of the minipumps. Autophagy was induced during regression of cardiac hypertrophy, as evidenced by an increase in microtubule-associated protein 1 light chain 3 (LC3)-II protein level. Then, we subjected cardiac-specific Atg5-deficient (CKO) and control mice (CTL) to angiotensin II infusion for 14 days. CKO and CTL developed cardiac hypertrophy to a similar degree without contractile dysfunction. Seven days after removal of the minipumps, CKO showed significantly less regression of cardiac hypertrophy compared with CTL. Regression of pressure overload-induced cardiac hypertrophy after unloading was also attenuated in CKO. These results suggest that autophagy is necessary for regression of cardiac hypertrophy during unloading of neurohumoral and hemodynamic stress. 相似文献
993.
Uladzimir Bildziukevich Lucie Rárová David Šaman Libor Havlíček Pavel Drašar Zdeněk Wimmer 《Steroids》2013
The current interest of the team has been focused on investigation of novel amides with potential cytotoxicity. The presented series of compounds was synthesized from selected steryl hemiesters and heteroaromatic amines. The synthetic protocol was designed in a simple and economic way, and divided into several general methodologies applicable to the compounds synthesized. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with tests on normal human fibroblasts. Most of the lanosterol-based compounds (3–5 and 7–10) showed medium to good cytotoxicity, while only two derivatives of cholesterol (18 and 19) showed medium cytotoxicity on human T-lymphoblastic leukemia cell line. The compounds 8 and 9 displayed the reasonable cytotoxicity among this series of amides, tested on the cell lines of T-lymphoblastic leukemia [14.5 ± 0.4 μM (8) and 18.5 ± 3.9 μM (9)], breast adenocarcinoma [19.5 ± 2.1 μM (8) and 23.1 ± 4.0 μM (9)] and cervical cancer [24.8 ± 5.3 μM (8) and 29.1 ± 4.7 μM (9)]. Only the compound 8 was adequately less active on normal human fibroblasts (40.4 ± 11.1 μM). 相似文献
994.
Alberto Busilacchi Antonio Gigante Monica Mattioli-Belmonte Sandra Manzotti Riccardo A.A. Muzzarelli 《Carbohydrate polymers》2013
The idea of using chitosan as a functional delivery aid to support simultaneously PRP, stem cells and growth factors (GF) is associated with the intention to use morphogenic biomaterials to modulate the natural healing sequence in bone and other tissues. For example, chitosan–chondroitin sulfate loaded with platelet lysate was included in a poly(d,l-lactate) foam that was then seeded with human adipose-derived stem cells and cultured in vitro under osteogenic stimulus: the platelet lysate provided to the bone tissue the most suitable assortment of GF which induces the osteogenic differentiation of the mesenchymal stem cells. PDGF, FGF, IGF and TGF-β were protagonists in the repair of callus fractures. The release of GF from the composites of chitosan–PRP and either nano-hydroxyapatite or tricalcium phosphate was highly beneficial for enhancing MSC proliferation and differentiation, thus qualifying chitosan as an excellent vehicle. A number of biochemical characteristics of chitosan exert synergism with stem cells in the regeneration of soft tissues. 相似文献
995.
Yudong Liu Ying Su Jiajia Wang Shenggang Sun Tao Wang Xian Qiao Xiaoqin Run Hui Li Zhihou Liang 《Neurochemistry international》2013
Preventing or reducing tau hyperphosphorylation is considered to be a therapeutic strategy in the treatment of Alzheimer’s disease (AD). Rapamycin may be a potential therapeutic agent for AD, because the rapamycin-induced autophagy may enhance the clearance of the hyperphosphorylated tau. However, recent rodent studies show that the protective effect of rapamycin may not be limited in the autophagic clearance of the hyperphosphorylated tau. Because some tau-related kinases are targets of the mammalian target of rapamycin (mTOR), we assume that rapamycin may regulate tau phosphorylation by regulating these kinases. Our results showed that in human neuroblastoma SH-SY5Y cells, treatment with rapamycin induced phosphorylation of the type IIα regulatory (RIIα) subunit of cAMP-dependent kinase (PKA). Rapamycin also induced nuclear translocation of the catalytic subunits (Cat) of PKA and decreases in tau phosphorylation at Ser214 (pS214). The above effects of rapamycin were prevented by pretreatment with the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126. In addition, these effects of rapamycin might not depend on the level of tau expression, because similar results were obtained in both the non-tau-expressing wild type human embryonic kidney 293 (HEK293) cells and HEK293 cells stably transfected with the longest isoform of recombinant human tau (tau441; HEK293/tau441). These findings suggest that rapamycin decreases pS214 via regulation of PKA. Because tau phosphorylation at Ser214 may prime tau for further phosphorylation by other kinases, our findings provide a novel possible mechanism by which rapamycin reduces or prevents tau hyperphosphorylation. 相似文献
996.
Oxidative-nitrosative stress and inflammatory responses are associated with endoplasmic reticulum (ER) stress in diabetic retinopathy, raising the possibility that disturbances in ER protein processing may contribute to CNS dysfunction in diabetics. Upregulation of the unfolded protein response (UPR) is a homeostatic response to accumulation of abnormal proteins in the ER, and the present study tested the hypothesis that the UPR is upregulated in two models for diabetes, cultured astrocytes grown in 25 mmol/L glucose for up to 4 weeks and brain of streptozotocin (STZ)-treated rats with diabetes for 1–7 months. Markers associated with translational blockade (phospho-eIF2α and apoptosis (CHOP), inflammatory response (inducible nitric oxide synthase, iNOS), and nitrosative stress (nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase, GAPDH) were not detected in either model. Nrf2 was present in nuclei of low- and high-glucose cultures, consistent with oxidative stress. Astrocytic ATF4 expression was not altered by culture glucose concentration, whereas phospho-IRE and ATF6 levels were higher in low- compared with high-glucose cultures. The glucose-regulated chaperones, GRP78 and GRP94, were also expressed at higher levels in low- than high-glucose cultures, probably due to recurrent glucose depletion between feeding cycles. In STZ-rat cerebral cortex, ATF4 level was transiently reduced at 4 months, and p-IRE levels were transiently elevated at 3 months. However, GRP78 and GRP94 expression was not upregulated, and iNOS, amyloid-β, and nuclear accumulation of GAPDH were not evident in STZ-diabetic brain. High-glucose cultured astrocytes and STZ-diabetic brain are relatively resistant to diabetes-induced ER stress, in sharp contrast with cultured retinal Müller cells and diabetic rodent retina. 相似文献
997.
Edbhergue V.L. Costa George C. Jimenez Catão T.F. Barbosa Romildo A. Nogueira 《Bioelectromagnetics》2013,34(2):114-121
Magnetic fields (MF) can alter the dynamic behavior of vascular tissue and may have a stimulatory or inhibitory effect on blood vessel growth. Fractal geometry has been used in several studies as a tool to describe the development of blood vascular networks. Due to its self‐similarity, irregularity, fractional dimension, and dependence on the scale of vessel dimensions, vascular networks can be taken as fractal objects. In this work, we calculated the fractal dimension by the methods of box counting (Dbc) and information dimension (Dinf) to evaluate the development of blood vessels of the yolk sac membrane (YSM) from quail embryos exposed to MF with a magnetic flux density of 1 mT and a frequency of 60 Hz. The obtained results showed that when the MF was applied to embryos aged between 48 and 72 h, in sessions of 2 h (6 h/day) and 3 h (9 h/day) with exposure intervals between 6 and 5 h, respectively, blood vascular formation was inhibited. Exposure sessions shorter than 2 h or longer than 3 h had no observable change on the vascular process. In contrast, the magnetic field had no observable change on the YSM vascular network for embryos aged between 72 and 96 h, irrespective of the exposure time. In conclusion, these results show a “window effect” regarding exposure time. Bioelectromagnetics 34:114–121, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
998.
999.
Kiyoshi Yamaguchi Kohsuke Takeda Hisae Kadowaki Ikumi Ueda Yoshio Namba Yasuyoshi Ouchi Hideki Nishitoh Hidenori Ichijo 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Diabetes mellitus is characterized by high blood glucose levels. Pancreatic ß cell death contributes to type 1 and type 2 diabetes. Akita mice, which harbor a human permanent neonatal diabetes-linked mutation (Cys96Tyr) in the insulin gene, are well established as an animal model of diabetes caused by pancreatic ß cell exhaustion. Mutant Insulin 2 protein (Ins2C96Y) induces endoplasmic reticulum (ER) stress and pancreatic ß cell death in Akita mice, although the molecular mechanism of InsC96Y-induced cell death remains unclear.Methods
We investigate the mechanisms of Ins2C96Y-induced pancreatic ß cell death in vitro and in vivo, using p38 inhibitor (SB203580), MIN6 cell (pancreatic ß cell line), Akita mice and apoptosis signal-regulating kinase 1 (ASK1) knockout mice.Results
The expression of InsC96Y activated the ASK1–p38 pathway. Deletion of ASK1 mitigated InsC96Y-induced pancreatic ß cell death and delayed the onset of diabetes in Akita mice. Moreover, p38 inhibitor suppressed InsC96Y-induced MIN6 cell death.Conclusions
These findings suggest that ER stress-induced ASK1–p38 activation, which is triggered by the accumulation of InsC96Y, plays an important role in the pathogenesis of diabetes.General significance
Pancreatic ß cell death caused by insulin overload appears to be involved in the pathogenesis of type 1 and type 2 diabetes. Inhibition of the ASK1–p38 pathway may be an effective therapy for various types of diabetes. 相似文献1000.