bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Nerve pericytes originating from the blood–nerve barrier expresses tight junctional molecules and transporters as barrier‐forming cells
Authors: Shimizu Fumitaka , Sano Yasuteru , Maeda Toshihiko , Abe Masa‐aki , Nakayama Hiroto , Takahashi Ri‐ichi , Ueda Masatsugu , Ohtsuki Sumio , Terasaki Tetsuya , Obinata Masuo , Kanda Takashi 
Published: June 2008

AbstractThe objective of this study was to establish pure blood–nerve barrier (BNB)‐derived peripheral nerve pericyte cell lines and to investigate their unique properties as barrier‐forming cells. We isolated peripheral nerve, brain, and lung pericytes from transgenic rats harboring the temperature‐sensitive simian virus 40 large T‐antigen gene. These cell lines expressed several pericyte markers such as α‐smooth muscle actin, NG2, osteopontin, and desmin, whereas they did not express endothelial cell markers such as vWF and PECAM. In addition, these cell lines expressed several tight junction molecules such as occludin, claudin‐12, ZO‐1, and ZO‐2. In particular, the expression of occludin was detected in peripheral nerve and brain pericytes, although it was not detected in lung pericytes by a Western blot analysis. An immunocytochemical analysis confirmed that occludin and ZO‐1 were localized at the cell–cell boundaries among the pericytes. Brain and peripheral nerve pericytes also showed significantly higher trans‐pericyte electrical resistance values and lower inulin clearances than lung pericytes. We considered that occludin localized at the cell–cell boundaries among the pericytes might mechanically stabilize the microvessels of the BNB and the blood–brain barrier. Furthermore, we also showed that these cell lines expressed many barrier‐related transporters. ABCG2, p‐gp, MRP‐1, and Glut‐1 were detected by a Western blot analysis and were observed in the cytoplasm and outer membrane by an immunocytochemical analysis. These transporters on pericytes might facilitate the peripheral nerve‐to‐blood efflux and blood‐to‐peripheral nerve influx transport of substrates in cooperation with those on endothelial cells in order to maintain peripheral nerve homeostasis. J. Cell. Physiol. 217: 388–399, 2008. © 2008 Wiley‐Liss, Inc.
A PPARs cross‐talk concertedly commits C6 glioma cells to oligodendrocytes and induces enzymes involved in myelin synthesis
Authors: Leisewitz Andrea V. , Urrutia Carolina R. , Martinez Gabriela R. , Loyola Gloria , Bronfman Miguel 
Published: June 2008

AbstractPeroxisome proliferator activated receptors (PPARs, α, β/δ, γ) control lipid homeostasis and differentiation in various tissues and tumor cells. PPARβ and PPARγ increase oligodendrocyte maturation in glial mixed populations and spinal cord oligodendrocytes, respectively, and PPARβ is known to modulate the activity of other PPARs. To assess a possible interaction between PPARs in glial cell differentiation we used the undifferentiated C6 glioma cell line as model. These cells express all three PPARs, but only PPARγ shows transcriptional activity in agonist‐based reporter gene assay. Agonist‐activated PPARγ up‐regulates oligodendrocyte markers, down‐regulates an astrocyte marker, and increases alkyl‐dihydroxyacetone phosphate synthase, enzyme involved in the synthesis of myelin‐rich plasmalogens. Similar effects are induced in PPARγ overexpressing cells, which in addition show PPARβ up‐regulation. PPARβ or PPARα agonists show no effect. Nevertheless, PPARβ overexpression up‐regulates PPARγ and commits C6 cells to oligodendrocytes; effect that is abrogated by a PPARγ antagonist or PPARγ interference RNA. Moreover, PPARβ overexpression also induces PPARα and its target genes, including acyl‐CoA oxidase, enzyme involved in very long chain fatty acid recycling, and in the synthesis of myelin components such as docosahexaenoic acid. These results indicate for the first time, that PPARs concertedly cooperate in C6 glioma cell differentiation to oligodendrocytes. Further, they suggest that active PPARβ might be essential for increasing oligodendrocyte distinctive markers and enzymes required for myelin synthesis in C6 glioma cells through up‐regulation of PPARγ and PPARα. J. Cell. Physiol. 217: 367–376, 2008. © 2008 Wiley‐Liss, Inc.
Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross‐talking with RANK signaling
Authors: Yi TacGhee , Lee Hye‐Lim , Cha Ji‐Hoon , Ko Soo‐Il , Kim Hye‐Jin , Shin Hong‐In , Woo Kyung‐Mi , Ryoo Hyun‐Mo , Kim Gwan‐Shik , Baek Jeong‐Hwa 
Published: June 2008

AbstractThe epidermal growth factor receptor (EGFR) functions in various cellular physiological processes such as proliferation, differentiation, and motility. Although recent studies have reported that EGFR signaling is involved in osteoclast recruitment and formation, the molecular mechanism of EGFR signaling for the regulation of osteoclastogenesis remains unclear. We investigated the role of the EGFR in osteoclast differentiation and survival and show that the expression of the EGFR was highly up‐regulated by receptor activator of nuclear factor‐κB ligand (RANKL) during osteoclast differentiation. EGFR‐specific tyrosine kinase inhibitors and EGFR knockdown blocked RANKL‐dependent osteoclast formation, suggesting that EGFR signaling plays an important role in osteoclastogenesis. EGFR inhibition impaired the RANKL‐mediated activation of osteoclastogenic signaling pathways, including c‐Jun N‐terminal kinase (JNK), NF‐κB, and Akt/protein kinase B (PKB). In addition, EGFR inhibition in differentiated osteoclasts caused apoptosis through caspase activation. Inhibition of the phosphoinositide‐3 kinase (PI3K)‐Akt/PKB pathway and subsequent activation of BAD and caspases‐9 and ‐3 may be responsible for the EGFR inhibition‐induced apoptosis. The EGFR physically associated with receptor activator of nuclear factor‐κB (RANK) and Grb2‐associated binder 2 (Gab2). Moreover, RANKL transactivated EGFR. These data indicate that EGFR regulates RANKL‐activated signaling pathways by cross‐talking with RANK, suggesting that the EGFR may play a crucial role as a RANK downstream signal and/or a novel type of RANK co‐receptor in osteoclast differentiation and survival. J. Cell. Physiol. 217: 409–422, 2008. © 2008 Wiley‐Liss, Inc.
Updating the effects of fatty acids on skeletal muscle
Authors: Silveira Leonardo R. , Fiamoncini Jarlei , Hirabara Sandro M. , Procópio Joaquim , Cambiaghi Tavane D. , Pinheiro Carlos Hermano J. , Lopes Lúcia R. , Curi Rui 
Published: June 2008

AbstractIn this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long‐chain acyl‐coenzyme A (LCA‐CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate‐1/2 (IRS), phosphatidylinositol‐3‐kinase, (PI3‐kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor‐kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNFα), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle. J. Cell. Physiol. 217: 1–12, 2008. © 2008 Wiley‐Liss, Inc.
Overexpression of spindlin1 induces metaphase arrest and chromosomal instability
Authors: Zhang Peng , Cong Bin , Yuan Hongfeng , Chen Lin , Lv Yang , Bai Cixian , Nan Xue , Shi Shuangshuang , Yue Wen , Pei Xuetao 
Published: June 2008

AbstractSpin/Ssty gene family is high conserved and very abundant transcript involved in gametogenesis, which was repeatedly detected in early embryo. Nevertheless, the biologic roles of the members are still largely unknown. Previously we have identified human gene spindlin1 as a homologue of the family from ovarian cancer cells, and reported that stable overexpression of spindlin1 could transform NIH3T3 cells and induce tumorigenesis in nude mouse. Here, we showed that spindlin1, as a nuclear protein, was relocated during mitosis. A fraction of spindlin1 proteins was dynamic distributed along mitotic spindle tubulin and enriched at midzone following anaphase entering. We also showed that transient overexpression of spindlin1 induced cell cycle delay in metaphase, caused mitotic spindle defects, and resulted in chromosome instability, micronucleus and multinuclear giant cells formation. Moreover, time‐lapse microscopy revealed that these cells arrested at metaphase for more than 3 h with chromosome nondisjunction or missegregation. Furthermore, Mad2 up‐regulation in these cells suggested that overexpression of spindlin1 may affect the bipolar spindle correctly attachment to chromosomes and activate spindle checkpoint. Taken together, these data demonstrated that excess spindlin1 protein may be detrimental for spindle microtubule organization, chromosomal stability and can potentially contribute to the development of cancer. J. Cell. Physiol. 217: 400–408, 2008. © 2008 Wiley‐Liss, Inc.
IL‐6/sIL‐6R enhances cathepsin B and L production via caveolin‐1‐mediated JNK‐AP‐1 pathway in human gingival fibroblasts
Authors: Yamaguchi Tomoko , Naruishi Koji , Arai Hideo , Nishimura Fusanori , Takashiba Shogo 
Published: June 2008

AbstractInterleukin (IL)‐6 has an important role in inflammatory diseases. Lysosomal enzymes cathepsins are widely expressed as cysteine proteases regulating inflammatory process. Caveolin‐1 (Cav‐1) is a scaffolding/regulatory membrane protein that interacts with signaling molecules. In this study, we investigated the role of Cav‐1 on (1) the productivity, and (2) the enzymatic activity of cathepsin B and L in human gingival fibroblasts (HGFs) treated with IL‐6 in the presence of soluble form of IL‐6 receptor (sIL‐6R). At first, we established the siRNA‐mediated Cav‐1 down‐regulating in vitro systems by transient transfection of Cav‐1 siRNA. The siRNA‐mediated Cav‐1 down‐regulated cells were treated with IL‐6/sIL‐6R for indicated times. Then, cell lysates were collected, and examined the IL‐6‐induced signaling pathway, cathepsin B and L production, and measurement of cathepsins activity. To investigate the cathepsin L activity, cathepsin‐(B + L) activity was measured after pretreatment with CA‐074Me, a specific inhibitor for cathepsin B. We found that IL‐6/sIL‐6R enhanced significantly both production and activity of cathepsin B and L in HGFs. Interestingly, IL‐6‐mediated phosphorylation of both p44/42 MAPK and JNK was dramatically suppressed in Cav‐1 down‐regulated HGFs treated with IL‐6/sIL‐6R. In addition, both production and activity of cathepsin B and L were also significantly suppressed. Importantly, we demonstrated that JNK inhibition, but not p44/42 MAPK inhibition, significantly diminished IL‐6/sIL‐6R‐induced cathepsin B and L production. Taken together, we concluded that IL‐6/sIL‐6R enhances cathepsin B and L production via IL‐6/sIL‐6R‐mediated Cav‐1‐JNK‐AP‐1 pathway in HGFs. Our findings indicate that Cav‐1 might be a therapeutic target for IL‐6‐mediated tissue degradation in periodontitis. J. Cell. Physiol. 217: 423–432, 2008. © 2008 Wiley‐Liss, Inc.
Continuous production of 1,2‐propanediol by the selective hydrogenolysis of solvent‐free glycerol under mild conditions
Authors: Huang Long , Zhu Yu‐Lei , Zheng Hong‐Yan , Li Yong‐Wang , Zeng Zhi‐Yong 
Published: June 2008

AbstractBACKGROUND: The conversion of glycerol to value‐added derivatives is now critical, owing to the large surplus of glycerol from biodiesel production. The main objective of this work is to develop a novel process for converting solvent‐free glycerol to 1,2‐propanediol.RESULTS: Several catalysts were screened for aqueous‐phase hydrogenolysis of glycerol in an autoclave. The most effective catalysts (Ni/Al2O3, Cu/ZnO/Al2O3) were further tested for vapor phase hydrogenolysis in a fixed‐bed. Ni/Al2O3 did not prove as effective for the production of 1,2‐propanediol because of the high selectivity to CH4 and CO. Over Cu/ZnO/Al2O3, glycerol was mainly converted to the desired 1,2‐propanediol and the reaction intermediate acetol. The production of 1,2‐propanediol was favoured at higher hydrogen pressure. At 190 °C and 0.64 MPa, near complete conversion of glycerol was achieved with 1,2‐propanediol selectivity up to 92%. In addition, a higher concentration (between 43.4% and 0.8%) of acetol was detected and an approximately stoichiometric relationship was found between acetol and 1,2‐propanediol.CONCLUSION: 1,2‐propanediol can be produced with high yields via the vapor phase hydrogenolysis of glycerol over Cu/ZnO/Al2O3. Furthermore, the mechanism of 1,2‐propanediol formation is suggested to proceed mainly through an acetol route over Cu/ZnO/Al2O3. Copyright © 2008 Society of Chemical Industry
Exogenous tumor necrosis factor‐α rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn
Authors: Youn Dong‐ho , Wang Haibin , Jeong Sung‐Jin 
Published: June 2008

AbstractThe proinflammatory cytokine tumor necrosis factor‐α (TNF‐α) is involved in the generation of inflammatory and neuropathic pain. This study investigated if TNF‐α has any effect on spinal synaptic and/or sensory transmission by using whole‐cell recordings of substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of adult rats and by using behavioral tests. After intrathecal administration of TNF‐α in adult rats, spontaneous hind paw withdrawal behavior and thermal hyperalgesia were rapidly induced (∼30 min), while mechanical allodynia slowly developed. Bath application of TNF‐α (0.1–1 nM, 8 min) depressed peak amplitude of monosynaptic Aδ and C fiber–evoked excitatory postsynaptic currents (EPSCs) without changing in holding currents and input resistances, whereas this application generally potentiated polysynaptic Aδ fiber‐evoked EPSCs. Moreover, the frequencies, but not the amplitudes, of spontaneous and miniature EPSCs and spontaneous inhibitory postsynaptic currents were significantly increased by bath‐applied TNF‐α in most of the SG neurons. The effects of TNF‐α on Aδ/C fiber–evoked monosynaptic and polysynaptic or spontaneous EPSCs were significantly blocked by 5 μM TNF‐α antagonist that inhibits TNF‐α binding to its type 1 receptor (TNFR1). Because this study also found high protein expression of TNFR1 in the adult dorsal root ganglion and no change of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) induced whole‐cell currents by TNF‐α, we conclude that presynaptic TNFR1 at Aδ/C primary afferent terminals contributes to the rapid alteration of synaptic transmission in the spinal SG, and the development of abnormal pain hypersensitivity by exogenous TNF‐α. © 2008 Wiley‐Liss, Inc.
Differential neuroprotective effects of carnosine, anserine, and N‐acetyl carnosine against permanent focal ischemia
Authors: Min Jiangyong , Senut Marie‐Claude , Rajanikant Krishnamurthy , Greenberg Eric , Bandagi Ram , Zemke Daniel , Mousa Ahmad , Kassab Mounzer , Farooq Muhammad U. , Gupta Rishi , Majid Arshad 
Published: June 2008

AbstractCarnosine (β‐alanyl‐L‐histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N‐acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N‐acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5‐triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18‐point‐based scale. Brain levels of carnosine were measured in treated mice using high‐performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle‐treated mice. These beneficial effects were maintained for 7 days post‐pMCAO. In contrast, compared with the vehicle‐treated group, bestatin‐treated mice displayed an increase in the severity of ischemic lesion, which was prevented by the addition of carnosine. These new data further characterize the neuroprotective effects of carnosine and suggest that carnosine may be an attractive candidate for testing as a stroke therapy. © 2008 Wiley‐Liss, Inc.
Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis
Authors: Ohta Yasuyuki , Kamiya Tatsushi , Nagai Makiko , Nagata Tetsuya , Morimoto Nobutoshi , Miyazaki Kazunori , Murakami Tetsuro , Kurata Tomoko , Takehisa Yasushi , Ikeda Yoshio , Asoh Sadamitsu , Ohta Shigeo , Abe Koji 
Published: June 2008

AbstractWhen fused with the protein transduction domain (PTD) derived from the human immunodeficiency virus TAT protein, proteins can cross the blood–brain barrier and cell membrane and transfer into several tissues, including the brain, making protein therapy feasible for various neurological disorders. We have constructed a powerful antiapoptotic modified Bcl‐XLprotein (originally constructed from Bcl‐XL) fused with PTD derived from TAT (TAT‐modified Bcl‐XL), and, to examine its clinical effectiveness in a mouse model of familial amyotrophic lateral sclerosis (ALS), transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation were treated by intrathecal infusion of TAT‐modified Bcl‐XL. We demonstrate that intrathecally infused TAT‐fused protein was effectively transferred into spinal cord neurons, including motor neurons, and that intrathecal infusion of TAT‐modified Bcl‐XLdelayed disease onset, prolonged survival, and improved motor performance. Histological studies show an attenuation of motor neuron loss and a decrease in the number of cleaved caspase 9‐, cleaved caspase 3‐, and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive cells in the lumbar cords of TAT‐modified Bcl‐XL‐treated G93A mice. Our results indicate that intrathecal protein therapy using a TAT‐fused protein is an effective clinical tool for the treatment of ALS. © 2008 Wiley‐Liss, Inc.
Abnormal growth of the corticospinal axons into the lumbar spinal cord of the hyt/hyt mouse with congenital hypothyroidism
Authors: Hsu Jung‐Yu C. , Stein Stuart A. , Xu Xiao‐Ming 
Published: June 2008

AbstractThyroid hormone deficiency may cause severe neurological disorders resulting from developmental deficits of the central nervous system. The mutant hyt/hyt mouse, characterized by fetal‐onset, life‐long hypothyroidism resulting from a point mutation of the thyroid‐stimulating hormone receptor of the thyroid gland, displays a variety of abnormalities in motor behavior that are likely associated with dysfunctions of specific brain regions and a defective corticospinal tract (CST). To test the hypothesis that fetal and neonatal hypothyroidism cause abnormal CST development, the growth of the CST was investigated in hypothyroid hyt/hyt mice and their euthyroid progenitors, the BALB/cByJ mice. Anterograde labeling with biotinylated dextran amine demonstrated a decrease in the number of CST axons in the hyt/hyt mouse at the first lumbar level at postnatal day (P) 10. After retrograde tracing with fast blue (FB), fewer FB‐labeled neurons were found in the motor cortex, the red nucleus, and the lateral vestibular nucleus of the hyt/hyt mouse. At the fourth lumbar level, the hyt/hyt mouse also showed smaller CST cross‐sectional areas and significantly lower numbers of unmyelinated axons, myelinated axons, and growth cones within the CST during postnatal development. At P10, the hyt/hyt mouse demonstrated significantly lower immunoreactivity of embryonic neural cell adhesion molecule in the CST at the seventh cervical level, whereas the expression of growth‐associated protein 43 remained unchanged. Our study demonstrated an abnormal development of the CST in the hyt/hyt mouse, manifested by reduced axon quantity and retarded growth pattern at the lumbar spinal cord. © 2008 Wiley‐Liss, Inc.
Transcriptional changes in insulin‐ and lipid metabolism‐related genes in the hippocampus of olfactory bulbectomized mice
Authors: Gass Peter , Leonardi‐Essmann Fernando , Zueger Maha , Spanagel Rainer , Gebicke‐Haerter Peter J. 
Published: June 2008

AbstractAffymetrix chips were used to perform a hypothesis‐free large‐scale screening of transcripts in the hippocampus of olfactory bulbectomized mice, an established animal model of depression. Because only 11 transcripts were significantly changed, the statistically subsequent 25 transcripts below the significance level were additionally included in a first round of qRT‐PCR evaluations. Furthermore, all 36 genes were then tested for mutual interactions or interactions with other molecules in a physiological context using PathwayArchitect software. Thirty of them were displayed in a network interacting with at least one partner molecule from the list or with other partner molecules known from the literature. All partner molecules from the most prominent 10 molecules of this network were then identified and put together into a new list. On those grounds, the hypothesis was made that metabolic network components of the insulin signaling pathway are perturbed in the disease. This pathway was subsequently tested by a second round of qRT‐PCR, adding also a few additional candidate molecules belonging to this pathway. It turned out that the key target—FABP7—fell into the group of transcripts not significantly regulated within the chip data, and another key target—IRS1—did not show up in the chip experiments at all. In conclusion, our data reveal a problem with adhering to statistical significances in microarray experiments, insofar as molecules important for the disease may fall into the range of statistical noise. This approach may also be useful to find new targets for pharmacotherapy in affective disorders. © 2008 Wiley‐Liss, Inc.