bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helix 12 in the human estrogen receptor (hER) is essential for the hER function by overcoming nucleosome repression in yeast
Authors: Gu Xiaohong 
Published: October 2002

AbstractWhen exogenous human estrogen receptor (hER) binds with estrogen, it can activate transcription of target genes in yeast cells. The estrogen dose‐response expression patterns in yeast are very similar to those in human cells. This implies that hER may function in yeast cells via mechanisms similar to those in human cells. In this study, Saccharomyces cerevisiae was used to dissect mechanisms of hER‐activated transcription in yeast. The hER contains two transcription activation domains: ER‐AF‐1 and ER‐AF‐2 (LBD or HBD). In both human and wild‐type yeast cells, hER must bind with estrogen in order to activate transcription. In those cells, ER‐AF‐2 is independently active upon hormone binding, but ER‐AF‐1 by itself is inactive. In a mutagenesis screen, we found a mutant strain in which the ER‐AF‐1 was independently active. It was determined that this mutant strain carried a Tup1 mutation. More interestingly, a small hER fragment ER‐AF‐0, containing neither ER‐AF‐1 nor ER‐AF‐2, was also fully active in the ΔTup1 cells. This suggests that in this strain, hormone binding is not required for transcription activation by hER. It is known that the Tup1/Ssn6 complex plays an important role in general transcription repression by protecting histone acetylation sites thus stabilizing nucleosomes. In the ΔTup1 cells, nucleosomes are known to be unstable because histones can be easily accessed by acetylase and cause nucleosome disassociation. Two point mutations in helix 12 (H12) in ER‐AF‐2, which abolished hER function in human cells, also completely abolished hER function in the wild‐type yeast cells. This suggested that H12 is essential for hER transcription activation function. However, hER with the H12 mutation is able to activate transcription in ΔTup1 cells. This indicates that the normal function of H12 is required for transcription activation by hER only if nucleosomes are not acetylated and are therefore stable. The results of this work suggest that there is a close relationship between hER function and nucleosome remodeling. It also provides insight about H12 activity and its functional relationship with other domains in hER. We propose here that H12 is essential for hER function by recruiting strong nucleosome remodeling proteins to the promoter region thus overcoming nucleosome repression. J. Cell. Biochem. 86: 224–238, 2002. © 2002 Wiley‐Liss, Inc.
Nitric oxide and prostaglandin E2 participate in lipopolysaccharide/interferon‐γ‐induced heme oxygenase 1 and prevent RAW264.7 macrophages from UV‐irradiation‐induced cell death
Authors: Chen Yen‐Chou , Shen Shing‐Chuan , Lee Woan‐Ruoh , Lin Hui‐Yi , Ko Ching‐Huai , Lee Tony J.F. 
Published: October 2002

AbstractInduction of heme oxygenase (HO)‐1 during inflammation has been demonstrated in many cell types, but the contribution of inflammatory molecules nitric oxide (NO) and prostaglandin E2 (PGE2) has remained unresolved. Here we show that NO donors including sodium nitroprusside (SNP) and spermine nonoate (SP‐NO), and PGE2 significantly stimulate HO‐1 expression in RAW264.7 macrophages, associated with alternative induction on NO and PGE2 in medium, respectively. NO donors also show the inductive effect on cyclo‐oxygenase 2 protein and PGE2 production. In the presence of lipopolysaccharide and interferon‐γ (LPS/IFN‐γ), HO‐1 protein was induced slightly but significantly, and SNP, SP‐NO, and PGE2 enhanced HO‐1 protein induced by LPS/IFN‐γ. L‐Arginine analogs N‐nitro‐L‐arginine methyl ester (L‐NAME) and N‐nitro‐L‐arginine (NLA) significantly block HO‐1 protein induced by LPS/IFN‐γ associated with a decrease in NO (not PGE2) production. And, NSAIDs aspirin and diclofenase dose dependently inhibited LPS/IFN‐γ‐induced HO‐1 protein accompanied by suppression of PGE2 (not NO) production. PD98059 (a specific inhibitor of MEKK), but not SB203580 (a specific inhibitor of p38 kinase), attenuated PGE2 (not SP‐NO) induced HO‐1 protein. Under UVC (100 J/m2) and UVB (50 J/m2) irradiation, PGE2 or SP‐NO treatment prevents cells from UVC or UVB‐induced cell death, and HO‐1 inhibitor tin protoporphyrin (SnPP) reverses the preventive effects of PGE2 and SP‐NO. The protective activity induced by PGE2 on UVC or UVB irradiation‐induced cell death was blocked by MAPK inhibitor PD98059 (not SB203580). These results demonstrated that inflammatory molecules NO and PGE2 were potent inducers of HO‐1 gene, and protected cells from UV‐irradiation‐induced cell death through HO‐1 induction. J. Cell. Biochem. 86: 331–339, 2002. © 2002 Wiley‐Liss, Inc.
Systemically administered rhBMP‐2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice
Authors: Turgeman Gadi , Zilberman Yoram , Zhou Shuanhu , Kelly Pam , Moutsatsos Ioannis K. , Kharode Yogendra P. , Borella Luis E. , Bex Frederick J. , Komm Barry S. , Bodine Peter V.N. , Gazit Dan 
Published: October 2002

AbstractOsteoporosis is a disease manifested in drastic bone loss resulting in osteopenia and high risk for fractures. This disease is generally divided into two subtypes. The first, post‐menopausal (type I) osteoporosis, is primarily related to estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related to aging. Decreased bone formation, as well as increased bone resorption and turnover, are thought to play roles in the pathophysiology of both types of osteoporosis. In this study, we demonstrate in murine models for both type I (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced bone formation is related to a decrease in adult mesenchymal stem cell (AMSC) number, osteogenic activity, and proliferation. Decreased proliferation is coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice. Recombinant human bone morphogenetic protein (rhBMP‐2) is a highly osteoinductive protein, promoting osteogenic differentiation of AMSCs. Systemic intra‐peritoneal (i.p.) injections of rhBMP‐2 into osteopenic mice were able to reverse this phenotype in the bones of these animals. Moreover, this change in bone mass was coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation as well as a decrease in apoptosis. Bone formation activity was increased as well. However, the magnitude of this response to rhBMP‐2 varied among different stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model), rhBMP‐2 systemic treatment also restored both articular and epiphyseal cartilage width to the levels seen in young mice. In summary, our study shows that AMSCs are a good target for systemically active anabolic compounds like rhBMP‐2. J. Cell. Biochem. 86: 461–474, 2002. © 2002 Wiley‐Liss, Inc.
Effects of alpha lipoic acid, ascorbic acid‐6‐palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats
Authors: Yilmaz Ökkeş , Özkan Yusuf , Yildirim Mehmet , Öztürk A. İhsan , Erşan Yasemin 
Published: October 2002

AbstractIn this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid‐6‐palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)‐induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D + ALA groups (P < 0.05), but its level reduced in D + FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D + AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In contrast, total unsaturated fatty acid level in D + ALA and D + FO groups was higher than control (P < 0.05). In conclusion, present data have confirmed that the combination of the ALA, AA6P, and FO have improvement effects on the recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in addition to this, oxidative stress was suppressed by ALA and AA6P, and unsaturated fatty acid degree was raised by the effects of ALA and FO. J. Cell. Biochem. 86: 530–539, 2002. © 2002 Wiley‐Liss, Inc.
Differential nuclear receptor signalling from DR4‐type response elements
Authors: Quack Marcus , Frank Christian , Carlberg Carsten 
Published: October 2002

AbstractNuclear receptors form a large family of highly related transcription factors that transform an incoming signal in the form of a lipophilic hormone into an activation of the basal transcriptional machinery. The specific recognition of nuclear receptor DNA binding sites, referred to as response elements (REs), determines the genes that can be regulated by nuclear hormones. In this study, it was shown that the complexes of the retinoid X receptor (RXR) with either the vitamin D3 receptor (VDR), the thyroid hormone receptor (T3R) or the liver X receptor (LXR) have comparable functionality on a RE of the rat pit‐1 gene that is formed by a direct repeat of two hexameric binding motifs spaced by 4 nucleotides (DR4). The sequence of two nucleotides 5′‐flanking the downstream binding motif of this DR4‐type RE and, interestingly, also those flanking the upstream motif were shown to have in part rather drastic and receptor‐specific effects on heterodimer complex formation on DNA. In particular, a downstream substitution into GA reduced the complex formation for LXR specifically, while upstream substitutions into AA or TA increase complex formation for LXR and, to a lesser extent, T3R. The preference of this in vitro complex formation was shown to correlate well with the functional activity of the nuclear receptors in living cells. The results of this study allow (i) a more detailed understanding of known REs, (ii) a more straightforward search for putative REs in newly identified promoter sequences, for example, of the whole human genome, and (iii) a more precise prediction of the hormone responsiveness of the respective genes. J. Cell. Biochem. 86: 601–612, 2002. © 2002 Wiley‐Liss, Inc.
Role of nuclear PKC δ in mediating caspase‐3‐upregulation in Jurkat T leukemic cells exposed to ionizing radiation
Authors: Cataldi Amelia , Miscia Sebastiano , Centurione Lucia , Rapino Monica , Bosco Domenico , Grifone Giovanna , Valerio Valentina Di , Garaci Francesco , Rana Rosalba 
Published: October 2002

AbstractThe response of Jurkat T cells to ionizing radiation (IR) includes cell cycle arrest and DNA damage, which lead to the occurrence of apoptosis. Here, we try to elucidate some of the early intracellular signals which control the induction of such a process upon IR exposure, addressing to examine the specific role of several PKC isoforms (δ, ε, ζ) and their subcellular distribution. Attention has been focused on the connections between nuclear PKC δ activation and the expression of cell death regulators (Bcl‐2 family proteins Bad, Bax and Bcl‐2) and cell death effector caspase‐3 (CPP32) which lead to the cleavage of cytoskeletal and nuclear proteins and induction of apoptosis. Altogether these results let us to conclude that PKC δ, potentiating the pro‐apoptotic effect of caspase 3, plays a key role in the cellular response to IR and thus can be considered a molecular target for therapy. © 2002 Wiley‐Liss, Inc.
MT1‐MMP, but not secreted MMPs, influences the migration of human microvascular endothelial cells in 3‐dimensional collagen gels
Authors: Koike Teruhiko , Vernon Robert B. , Hamner Margaret A. , Sadoun Eman , Reed May J. 
Published: October 2002

AbstractMatrix metalloproteinases (MMPs) and their specific inhibitors the TIMPs play significant roles in angiogenesis. We investigated how the expression of specific MMPs and TIMPs by human microvascular endothelial cells (hmECs) was modulated by culture of the cells in 3‐dimensional (3D) type I collagen gels versus 2‐dimensional (2D) collagen‐coated surfaces. By reverse‐transcription polymerase chain reaction (RT‐PCR), levels of mRNA for MMPs‐1, ‐2, and ‐13, MT1‐MMP, and TIMPs‐1 and ‐2 were similar in 2D versus 3D cultures. By Western blot assay, TIMP‐1 and proMMP‐1 were present and were expressed similarly in media from 2D versus 3D cultures, whereas active MMPs‐1, ‐9, and ‐13 were not detected. Active MMP‐13 was present in cell lysates (CL) and was increased in lysates from 3D cultures relative to 2D cultures. Relative to 2D cultures, CL and media from 3D cultures exhibited a decrease in expression of TIMP‐2 and an increased conversion of proMMP‐2 and proMT1‐MMP to active or processed forms. The MMP inhibitor GM6001 interfered with the migration of hmECs in 3D cultures, but not in 2D cultures. Addition of active MMP‐1 or blocking antibodies to TIMP‐1 did not affect the migration of hmECs in 3D collagen. Migration in 3D collagen was decreased by TIMP‐2 (an inhibitor of MT1‐MMP), but not by TIMP‐1 (a poor inhibitor of MT1‐MMP, but an efficient inhibitor of MMP‐2). Collectively, our data indicate that MT1‐MMP contributes significantly to the movement of hmECs through 3D collagen, in contrast to secretory‐type MMPs‐1, ‐2, ‐9, and ‐13, which are not critical for this movement. J. Cell. Biochem. 86: 748–758, 2002. © 2002 Wiley‐Liss, Inc.
Spectral density calculation by using the Chebyshev expansion
Authors: Ikegami Tsutomu , Iwata Suehiro 
Published: October 2002

AbstractA method to calculate the spectral density of any state vectors with respect to a set of eigenstates of a Hamiltonian is presented. A spectral density operator, whose expectation value on the state vector gives the spectral density, is evaluated indirectly by using the Chebyshev expansion method. A spectral transformation function is introduced to improve resolution at the low energy region, at the expense of the one at the higher region. The predissociation spectrum of CO+ is calculated to demonstrate the method. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 310–318, 2002
Distance and exposure dependent effective dielectric function
Authors: Mallik Buddhadeb , Masunov Artem , Lazaridis Themis 
Published: October 2002

AbstractIn an effort to develop a dielectric screening function for molecular dynamics simulations of biomolecules in implicit solvent, effective dielectric constants (Deff) for a large number of atom pairs in a typical globular protein are calculated by continuum electrostatics. Plots of Deff versus the intercharge distance are in general sigmoidal with the characteristics of the curve depending on the distance of the two charges from the dielectric boundary and, secondarily, on the extent to which the area surrounding each charge is occupied by solvent (the “exposure”). The Deff values were fitted to an empirical, analytical function of these parameters that reproduces the data reasonably well, although considerable scatter exists in the range of Deff from 30 to 80. In the system used for parameterization, the mean square deviation of electrostatic interaction energies with this function is 0.48 kcal/mol, compared to 1.45 for an analytical Generalized Born model and 1.52 for the linear distance‐dependent dielectric model. When tested in other proteins of varying size and compactness, the present function is superior to both of the above models, except for a fully unfolded polypeptide chain, where the Generalized Born model is superior. © 2002 Wiley Periodicals, Inc. J Comput Chem 11: 1090–1099, 2002
An analysis of the influence of insurance sponsorship on MMPI changes among patients with chronic pain
Authors: Fow Neil R. , Dorris Gregory , Sittig Michael , Smith‐Seemiller Laura 
Published: October 2002

AbstractPretreatment and posttreatment MMPI scores of 821 patients who completed a chronic pain program were submitted to a multivariate analysis of variance, examining the effects of age, gender, and insurance sponsorship. With the exception of scale 9, all clinical scales were significantly lower at posttreatment. Only the sponsorship variable was found to be a moderator variable for these treatment effects, with decreases on scales 1, 2, 3, and 0 attenuated in subjects with Worker's Compensation sponsorship compared to other sponsorship. Suggestions for further multivariate research with this population are discussed. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 827–832, 2002.
Protective factors against substance use among Asian American youth: A test of the peer cluster theory
Authors: Kim Irene J. , Zane Nolan W. S. , Hong Sehee 
Published: October 2002

AbstractFew viable theoretical models of risk and protective factors for adolescent substance use have been empirically tested on diverse populations. The purpose of this study was twofold. First, the cross‐cultural validity of Oetting and Beauvais' (1987) peer cluster theory was tested on a sample of Asian American youth. Second, the effect of youths' immigration experience on the relationship among the protective factors was examined. Results showed partial support for the validity of the peer cluster model for this sample. As hypothesized, the peer domain variable was significantly related to substance use, while the family domain variable served as a protective factor against substance use. However, the school domain variable did not have any direct or indirect effects on substance use. There were no significant differences in the path model when the sample was split according to youth immigrant status. Implications for substance use prevention are discussed. © 2002 Wiley Periodicals, Inc.
Does p53 affect organismal aging?
Authors: Donehower Lawrence A. 
Published: October 2002

AbstractThe p53 protein plays a critical role in the prevention of cancer. It responds to a variety of cellular stresses to induce either apoptosis, a transient cell cycle arrest, or a terminal cell cycle arrest called senescence. Senescence in cultured cells is associated with augmented p53 activity and abrogation of p53 activity may delay in vitro senescence. Increasing evidence suggests that p53 may also influence aspects of organismal aging. Several mutant mouse models that display alterations in longevity and aging‐related phenotypes have defects in genes that alter p53 signaling. Recently, my laboratory has developed and characterized a p53 mutant mouse line that appears to have an enhanced p53 response. These p53 mutants exhibit increased cancer resistance, yet have a shortened longevity and display a number of early aging‐associated phenotypes, suggesting a role for p53 in the aging process. The nature of the aging phenotypes observed in this p53 mutant line is consistent with a model in which aging is driven in part by a gradual depletion of stem cell functional capacity. © 2002 Wiley‐Liss, Inc.
Mitochondria, the killer organelles and their weapons
Authors: Ravagnan Luigi , Roumier Thomas , Kroemer Guido 
Published: October 2002

AbstractApoptosis is a cell‐autonomous mode of death that is activated to eradicate superfluous, damaged, mutated, or aged cells. In addition to their role as the cell's powerhouse, mitochondria play a central role in the control of apoptosis. Thus, numerous pro‐apoptotic molecules act on mitochondria and provoke the permeabilization of mitochondrial membranes. Soluble proteins contained in the mitochondrial intermembrane space are released through the outer membrane and participate in the organized destruction of the cell. Several among these lethal proteins can activate caspases, a class of cysteine proteases specifically activated in apoptosis, whereas others act in a caspase‐independent fashion, by acting as nucleases (e.g., endonuclease G), nuclease activators (e.g., apoptosis‐inducing factor), or serine proteases (e.g., Omi/HtrA2). In addition, mitochondria can generate reactive oxygen species, following uncoupling and/or inhibition of the respiratory chain. The diversity of mitochondrial factors participating in apoptosis emphasizes the central role of these organelles in apoptosis control and unravels novel mechanisms of cell death execution. © 2002 Wiley‐Liss, Inc.
Cystathionine β‐synthase is coordinately regulated with proliferation through a redox‐sensitive mechanism in cultured human cells and Saccharomyces cerevisiae
Authors: Maclean Kenneth N. , Janošík Miroslav , Kraus Eva , Kožich Viktor , Allen Robert H. , Raab Beverly K. , Kraus Jan P. 
Published: October 2002

AbstractCystathionine β‐synthase (CBS) catalyzes the condensation of serine with homocysteine to form cystathionine and occupies a crucial regulatory position between the methionine cycle and the biosynthesis of cysteine by transsulfuration. Analysis of CBS activity under a variety of growth conditions indicated that CBS is coordinately regulated with proliferation in both yeast and human cells. In batch cultures of Saccharomyces cerevisiae, maximal CBS activities were observed in the exponential phase of cells grown on glucose, while growth‐arrested cultures or those growing non‐fermentatively on ethanol or glycerol had ∼3‐fold less activity. CBS activity assays and Western blotting indicated that growth‐specific regulation of CBS is evolutionarily conserved in a range of human cell lines. CBS activity was found to be maximal during proliferation and was reduced two‐ to five‐fold when cells became quiescent at confluence. In cultured HepG2 cells, the human CBS gene is induced by serum and basic fibroblast growth factor and is downregulated, but not abolished, by contact inhibition, serum‐starvation, nutrient depletion, or the induction of differentiation. Consequently, for certain cell types, CBS may represent a novel marker of both differentiation and proliferation. The intracellular level of the CBS regulator compound, S‐adenosylmethionine, was found to reflect the proliferation status of both yeast and human cells, and as such, constitutes an additional mechanism for proliferation‐specific regulation of human CBS. Our data indicates that screening compounds for the ability to affect transsulfuration in cultured cell models must take proliferation status into account to avoid masking regulatory interactions that may be of significance in vivo. © 2002 Wiley‐Liss, Inc.