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H Kim

Publications and source records attributed to H Kim.

At least 523 records · Page 29Linked to original sources
PubMed1998

Evidence of protein kinase C translocation by ischemic preconditioning in global ischemia model.

We tested recent evidence that ischemic preconditioning (PC) involves in translocation of protein kinase C (PKC) from the cytosol to myocyte membrane. Isolated Langendorff-perfused rabbit hearts (n=96) were subjected to 60 or 45 min of ischemia (I) and 120 min of reperfusion (R) with or without PC (4 cycles of 5 min I and 5 min R; or single dose of 5 min I and 10 min R), respectively. Left ventricular function and infarct size (IS) were measured; myocardial cytosolic and membrane PKC activity were determined by 32P-gamma-ATP incorporation into PKC-specific peptide. PC enhanced improvement of functional recovery and reduced IS (26.9+/-1.4% versus 15.3+/-1.9%, p<0.01, in 60 min of I; 18.3+/-2.6% versus 8.6+/-2.5%, p<0.05, in 45 min of I); cytosolic PKC activity decreased 74% of total activity (p<0.05) both in 60 and 45 min of I; membrane PKC activity increased (1.7-fold of baseline, p<0.01, in 60 min of I; 1.8-fold, p<0.01, in 45 min of I; 1.5-fold, p<0.05, in 60 of min I and 120 min of R). From these results, it is concluded that translocation of PKC from the cytosol to myocyte membranes is an important mechanism responsible for PC effect.

Animals↗
PubMed1998

Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin.

To determine whether multidrug resistance (MDR1) P-glycoprotein (Pgp) expression correlated with clinical MDR1-related drug resistance, we established a protocol for quantitative measurement of Pgp expression and in vitro drug resistance in doxorubicin resistant MCF7 breast cancer cell lines and 359 freshly resected specimens of breast carcinoma. Pgp expression was detected with 4E3, UIC2, and JSB-1 monoclonal antibodies using flow cytometry and immunohistochemistry (IHC). Pgp function was determined using PSC833 in a drug resistance-reversal assay and with a three-dimensional agarose-based extreme drug resistance assay. MCF7 calibrator cell lines expressed Pgp, which was functional and in proportion to the degree of drug resistance. Flow cytometry, UIC2 shift assays, IHC scores, and determination of absorbance products by image analysis were all highly correlated (r > 0.9). Overall Pgp expression increased from 11% in untreated patients to 30% in patients who had previously received chemotherapy. Compared with Pgp-negative tumors, a significant increase in doxorubicin and Taxol resistance was seen for breast cancers that expressed Pgp, regardless of prior treatment. A strong correlation between the degree of Pgp expression and in vitro resistance to Taxol and doxorubicin (but not to 5-fluorouracil) was found when either IHC scores or image analysis-based methods were used to quantify Pgp expression (n = 185, P < 0.0001). The degree of Pgp expression strongly correlated with the degree of drug resistance in the clinical specimens studied. These data suggest that (a) Pgp contributes to clinical MDR1-related drug resistance, and (b) both intrinsic and acquired expression of Pgp in breast cancer may contribute in part to therapeutic failure and relapse.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells.

Interleukin-6 (IL-6) induces the expression of acute phase plasma protein genes in hepatic cells through the action of gp130, the signal-transducing subunit of the IL-6 receptor. To identify whether the transmembrane domain of gp130 is required for signaling function, cytoplasmic forms of gp130 were constructed that consisted of the tetramerizing N-terminal domain of Bcr linked to the transmembrane and cytoplasmic domains of gp130 (Bcr/gp130) or just to the cytoplasmic domain of gp130 (Bcr/gp130DeltaTM). The expression and function of both constructs were determined in transiently transfected COS-1 and HepG2 cells. Bcr/gp130 is capable of interacting with JAK1, JAK2, and TYK2; is constitutively active; and induces gene expression through IL-6-responsive elements. In contrast, Bcr/gp130DeltaTM, while expressed at a higher level than Bcr/gp130 and still able to interact with JAK1, is ineffective in recruiting the endogenous signal transduction pathways for inducing gene expression. However, Bcr/gp130DeltaTM initiates partial signaling in the presence of overexpressed JAK1 and TYK2, but not JAK2. The data suggest that the transmembrane domain of gp130 is necessary for signal transduction and determines the interaction with members of the Janus kinase family.

Animals↗
PubMed1997

Deletion of the M6P/IGF2r gene in primary hepatocellular carcinoma.

To evaluate the different alteration patterns of the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) gene in hepatocellular carcinoma (HCC), 41 HCCs were screened for homozygous deletion and loss of heterozygosity (LOH) at the M6P/IGF2r gene with a dinucleotide repeat polymorphic marker. Of these, three (8.8%) were heterozygous and LOH was observed in two (66.7%) of these informative cases. Five (14.7%) out of 34 informative cases showed homozygous deletions for the dinucleotide repeat polymorphic marker. The frequent allelic loss and homozygous deletion of the M6P/ IGF2r gene suggest that the M6P/IGF2r gene functions as a tumor suppressor gene in the development of HCC.

Carcinoma, Hepatocellular↗
PubMed1997

Nitric oxide modulates the c-Jun N-terminal kinase/stress-activated protein kinase activity through activating c-Jun N-terminal kinase kinase.

Nitric oxide is a signaling molecule that has a broad range of physiological functions, including neurotransmission, macrophage activation, and vasodilation. The mechanism by which nitric oxide regulates signal transduction mediating diverse biological activities is not fully understood, however. Here, we demonstrate that nitric oxide induced the stimulation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in intact cells. Exposure of cultured HEK293 cells to sodium nitroprusside, a nitric oxide releasing agent, resulted in the stimulation of JNK1 activity. The sodium nitroprusside-induced stimulation of JNK1 activity was abolished by treatment of cells with N-acetylcysteine. Nitric oxide production from HEK293 cells ectopically expressing nitric oxide synthases resulted in the stimulation of JNK1 activity, while JNK1 stimulation in nitric oxide synthase-overexpressing cells was abrogated by a nitric oxide synthase inhibitor, NG-nitro-L-arginine. Furthermore, exposure of cells to sodium nitroprusside resulted in the stimulation of JNK kinase (JNKK1/SEK1). Taken together, our data suggest that nitric oxide modulates the JNK activity through activating JNKK1/SEK1.

Animals↗
PubMed1997

Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human tumors in Asia and Africa. The molecular genetic changes involving both protooncogenes and tumor suppressor genes are known to be involved in hepatocarcinogenesis, but the roles of the known tumor suppressor genes in hepatocarcinogenesis are not fully elucidated. In this study, the authors analyzed the loss of heterozygosity (LOH) of known tumor suppressor genes in HCC and evaluated the relationship between LOH of tumor suppressor genes and clinicopathologic features. METHODS: The authors assessed the LOH of the 10 known tumor suppressor genes (VHL, APC, EXT1, WT1, Rb1, p53, BRCA1, nm23, DPC4, and DCC) with microsatellite markers in 29 consecutively resected HCC specimens. RESULTS: The authors found frequent LOH of tumor suppressor genes in HCC. Twenty five of 29 cases (86%) had LOH of tumor suppressor genes and 17 cases (59%) had LOHs involving 2-4 tumor suppressor genes. Among the tumor suppressor genes, frequent LOH was noted in the p53 (66%), Rb1 (33%), EXT1 (33%), and APC (20%) genes. LOH of the p53 gene and multiple LOH of the tumor suppressor genes were more frequent in poorly differentiated HCCs (P = 0.02). CONCLUSIONS: The LOH of tumor suppressor genes is frequent in HCCs and LOH of the p53 gene and accumulated LOHs are related to poorly differentiated HCC. Abnormalities of the p53 gene or the accumulated abnormalities of the tumor suppressor genes may play a role in the aggressive progression of HCC.

Adult↗
PubMed1997

Molecular characterization of a nonsuppressible allele (prC4) of the Drosophila purple gene.

Purple gene encodes 6-pyruvoyl tetrahydropterin synthase (PTP synthase) in Drosophila. The enzyme PTP synthase catalyzes the conversion of dihydroneopterin triphosphate (H2-NTP) to 6-pyruvoyl tetrahydropterin (PTP), an important intermediate for pterin compounds. The extreme purple mutant, prC4, shows a very low activity of PTP synthase. The mutant purple gene has been cloned by screening with the subgenomic library of prC4. The size and expression level of PTP synthase gene transcripts in prC4 were almost the same as those of the wild type. The genomic DNA was also examined in the purple region by Southern blot analysis, but no changes in restriction pattern could be detected. Compared with the wild type PTP synthase sequence, the mutant PTP synthase of prC4 showed three missense mutations: the replacement of alanine 7 by serine (A7S), leucine 9 by phenylalanine (L9P), and aspartic acid 168 by glycine (D168G). Significance of these mutations was discussed in relation to the formation of the oligomeric structure of PTP synthase.

Alleles↗
PubMed1997

Conformational change of cytochrome P450 1A2 induced by phospholipids and detergents.

Recently, it was reported that the activity of rabbit P450 1A2 is markedly increased at elevated salt concentration (Yun, C-H., Song, M., Ahn, T., and Kim, H. (1996) J. Biol. Chem. 271, 31312-31316). The activity increase of P450 1A2 coincides with the raised alpha-helix content and decreased beta-sheet content. The presence of phospholipid magnified this effect. Here, possible structural change of rabbit P450 1A2 accompanying the phospholipid-induced increase in its enzyme activity was investigated by circular dichroism, fluorescence spectroscopy, and absorption spectroscopy. Studies with the reconstituted system supported by cumene hydroperoxide or NADPH showed that the P450 1A2 activities were found to be dependent on the head group and hydrocarbon chain length of phospholipid. Phosphatidylcholines having short hydrocarbon chains with a carbon number of 8-12 were very efficient for reconstitution of the P450-catalyzed reactions supported by both cumene hydroperoxide and NADPH. It was found that the phospholipid increased the alpha-helix content and lowered the beta-sheet content of P450. Intrinsic fluorescence intensity is also increased in the presence of phospholipid. The low spin iron configuration of P450 1A2 shifted toward the high spin configuration by most of the phospholipids in the endoplasmic reticulum. Some synthetic phospholipids having short hydrocarbon chains with a carbon number of 10-12 caused a shift in the spin equilibrium of P450 1A2 toward low spin. The effect of detergents on the activity and conformation of P450 1A2 was also studied. It was found that the addition of detergents to P450 1A2 solution increased the enzyme activity of P450 1A2. Detergents also increased the alpha-helix content and lowered the beta-sheet content of P450 1A2. Intrinsic fluorescence emissions also increased with the presence of detergents. Octyl glucoside and deoxycholate caused a shift toward high spin. On the other hand, cholate caused a shift toward low spin. It was found that the activity increase of rabbit P450 1A2 coincides with the conformational change including raised alpha-helix content. It is proposed that the interaction with the phospholipid molecules surrounding P450 1A2 in the endoplasmic reticulum is important for a functional conformation of P450 1A2 in a monooxygenase system including NADPH-P450 reductase.

Animals↗
PubMed1997

Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria.

On the basis of x-ray diffraction data to a resolution of 2.9 angstroms, atomic models of most protein components of the bovine cytochrome bc1 complex were built, including core 1, core 2, cytochrome b, subunit 6, subunit 7, a carboxyl-terminal fragment of cytochrome c1, and an amino-terminal fragment of the iron-sulfur protein. The positions of the four iron centers within the bc1 complex and the binding sites of the two specific respiratory inhibitors antimycin A and myxothiazol were identified. The membrane-spanning region of each bc1 complex monomer consists of 13 transmembrane helices, eight of which belong to cytochrome b. Closely interacting monomers are arranged as symmetric dimers and form cavities through which the inhibitor binding pockets can be accessed. The proteins core 1 and core 2 are structurally similar to each other and consist of two domains of roughly equal size and identical folding topology.

Animals↗
PubMed1997

Oncostatin M and leukemia inhibitory factor do not use the same functional receptor in mice.

Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are members of the interleukin-6 (IL-6) subfamily of cytokines that use a common signal transducer gp130. Human OSM (hOSM) and LIF share a functional high-affinity receptor that is composed of gp130 and LIF receptor beta subunit (LIFRbeta). A second high-affinity receptor for hOSM was recently found to be formed by gp130 and the hOSM receptor beta subunit. However, the nature of murine OSM (mOSM) and its receptors has remained unknown. Using the recently cloned mOSM cDNA, we produced recombinant mOSM and studied its biological activity and receptor structure. Murine hematopoietic cell lines M1 and DA1.a, an embryonic stem cell line CCE, and Ba/F3 transfectants expressing gp130 and LIFRbeta responded to murine LIF (mLIF) and hOSM equally well, while these cells responded to mOSM only at a 30-fold to 100-fold higher concentration than those of mLIF and hOSM. In contrast, NIH3T3 cells responded to mOSM, but not to mLIF and hOSM. Scatchard plot analyses showed that mOSM bound to gp130 with low-affinity (kd = 2.8 to 4.2 nmol/L) and that the binding affinity did not increase in the presence of LIFRbeta. However, mOSM bound to NIH3T3 cells with high-affinity (kd = 660 pmol/L), whereas mLIF did not bind to NIH3T3 cells at all. These results indicate that unlike hOSM, mOSM and mLIF do not share the same functional receptor, and mOSM delivers signals only through its specific receptor complex. Further studies in mice will define the physiological roles of OSM.

Animals↗
PubMed1997

RNA helicase activity of Escherichia coli SecA protein.

SecA protein of Escherichia coli (E. coli), an ATPase essential for the translocation of precursor proteins, was found to have an additional activity of RNA helicase. This RNA unwinding activity of SecA was tested with two kinds of RNA duplex with different predicted stability. Each of these duplexes is consisted of two strands of unequal length with single-stranded ends. The RNA helicase activity of SecA required ATP and divalent cations. Confirmation of this activity came from the inhibition of unwinding of the RNA duplex when SecA was preincubated with its own polyclonal antibody. The biological significance of the RNA helicase activity of E. coli SecA protein is discussed.

Adenosine Triphosphatases↗
PubMed1997

The carboxyl-terminal region of STAT3 controls gene induction by the mouse haptoglobin promoter.

Haptoglobin (HP) is one of the major acute phase plasma proteins in the mouse, and its synthesis is additively induced by interleukin (IL)-6 and glucocorticoids. STAT3 serves as the mediator of the IL-6 receptor signal and appears to contribute to the transcriptional induction of acute phase protein genes. The carboxyl-terminal region of STAT3, consisting of an acidic domain and containing a serine phosphorylation site, has been proposed to contribute to the induction process. To assess the role of STAT3 in the transcriptional control of the HP promoter, we applied two mutant forms of STAT3: one with a deletion of the carboxyl-terminal 55 amino acid residues, STAT3Delta55C, and the other with a substitution of serine 727 to alanine, STAT3SA. Like the wild-type STAT3, both mutant STAT3 forms are activated by the signal-transducing subunit of the IL-6 receptor, gp130, or by co-transfected IL-3 receptor. Ectopic expression and activation of wild-type STAT3 or STAT3SA in HepG2 hepatoma cells similarly enhance transcription through the IL-6-response element of the HP promoter. This enhancement is specific for STAT3 and cannot be reproduced by STAT1 or STAT5. In contrast, STAT3Delta55C inhibits IL-6-induced transcriptional activation. Interestingly, whereas receptor-activated STAT3 also enhances stimulation of the haptoglobin promoter by dexamethasone through the glucocorticoid receptor, activated STAT3Delta55C reduces the regulation below the level achieved by the glucocorticoid receptor alone. This transdominant action by STAT3Delta55C is dependent on a functional IL-6-responsive element. The data suggest that the carboxyl-terminal domain, but not its serine phosphorylation site of STAT3, is required for transcription as part of the hematopoietin receptor signaling as well as for cooperation with other transcription factors such as the glucocorticoid receptor.

Alanine↗
PubMed1997

Are subjects' perceptual asymmetries on auditory and visual language tasks correlated?: a meta-analysis.

A number of studies have investigated the correlation between subjects' perceptual asymmetries on auditory and visual language tasks. With few exceptions, these studies have found low, nonsignificant correlations between the two types of perceptual asymmetries. However, variations in subjects' perceptual asymmetries on these tasks reflect not only individual differences in language lateralization but also several extraneous variables (e.g., random errors, individual differences in left-right attentional biases). Thus, low correlations between the two types of asymmetries may reflect "masking" by these extraneous variables rather than a "true" cross-modal dissociation. Consistent with this view, a meta-analysis of prior studies revealed a small, but significant correlation between the two types of asymmetries for left-handers. The correlation was nonsignificant for right-handers, presumably reflecting stronger attenuation caused by limited variability in language lateralization in this group. Possible factors mediating significant correlations between the two types of perceptual asymmetries include certain language processes shared by the two types of tasks, cross-modal consistency in individual differences in lateralization of certain modality-specific language processes, and cross-modal consistency in individual differences in left-right attentional biases.

Attention↗