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991.
Jung Hwa Oh Jung Tae Lee Eun Sun Yang Jong-Soo Chang Dong Sun Lee Sang Hyun Kim Yung Hyun Choi Jong-Wook Park Taeg Kyu Kwon 《Apoptosis : an international journal on programmed cell death》2009,14(11):1378-1386
Kahweol, the coffee-specific diterpene, has been reported for its tumor cell growth inhibitory activity and anti-carcinogenic
activity. The mechanism by which kahweol initiates apoptosis remains poorly understood. In the present study, we investigated
the effect of kahweol on the apoptotic pathway in U937 human promonocytic cells. We show that kahweol induces apoptosis in
association with the activation of caspase 3 and cytochrome c release from the mitochondria to the cytosol, as well as down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1
and XIAP). Kahweol altered the phosphorylation state of members of the MAPKs and Akt. Ectopic expression of Bcl-2 or constitutive
active Akt (myr-Akt) in U937 cells attenuates kahweol-induced apoptosis. In addition, we have also shown that JNK and Akt
signal pathway plays a crucial role in kahweol-induced apoptosis in U937 cells. Taken together, our results show the activity
of kahweol to modulate multiple components in apoptotic response of human leukemia cells and raise the possibility a novel
therapeutic strategy in hematological malignancies. 相似文献
992.
Ida Bjrkgren Sarah Mendoza Dong Hwa Chung Monika Haoui Natalie True Petersen Polina V. Lishko 《The Journal of general physiology》2021,153(10)
The choroid plexus (CP) epithelium secretes cerebrospinal fluid and plays an important role in healthy homeostasis of the brain. CP function can be influenced by sex steroid hormones; however, the precise molecular mechanism of such regulation is not well understood. Here, using whole-cell patch-clamp recordings from male and female murine CP cells, we show that application of progesterone resulted in specific and strong potentiation of the inwardly rectifying potassium channel Kir7.1, an essential protein that is expressed in CP and is required for survival. The potentiation was progesterone specific and independent of other known progesterone receptors expressed in CP. This effect was recapitulated with recombinant Kir7.1, as well as with endogenous Kir7.1 expressed in the retinal pigment epithelium. Current-clamp studies further showed a progesterone-induced hyperpolarization of CP cells. Our results provide evidence of a progesterone-driven control of tissues in which Kir7.1 is present. 相似文献
993.
No Association Between p73 G4C14-to-A4T14 Polymorphism and the Risk of Lung Cancer in a Korean Population 总被引:1,自引:0,他引:1
Choi JE Kang HG Chae MH Kim EJ Lee WK Cha SI Kim CH Jung TH Park JY 《Biochemical genetics》2006,44(11-12):543-550
A member of the p53 family, p73 may play an important role in the development of lung cancer. Variations in the DNA sequence in the p73 gene can lead to alterations in the production of p73 and/or activity, which can affect an individual's susceptibility to lung cancer. To test this hypothesis, this study examined the association between the G4C14-to-A4T14 polymorphism in the p73 gene and the risk of lung cancer in a Korean population. The p73 G4C14-to-A4T14 genotypes were determined in 582 lung cancer patients and 582 healthy age- and gender-matched control subjects. Compared with the GC/GC genotype, the GC/AT and the AT/AT genotypes were not significantly associated with the risk of lung cancer [adjusted odds ratio (OR) = 1.08, 95% confidence interval (CI) = 0.84-1.38; and adjusted OR = 1.37, 95% CI = 0.83-2.24, respectively]. In addition, the risk estimate for the combined variant genotype (GC/AT + AT/AT) was similar to that of the GC/GC genotype (a dominant model for the AT allele, adjusted OR = 1.12, 95% CI = 0.88-1.41). These results suggest that the p73 G4C14-to-A4T14 polymorphism does not significantly affect susceptibility to lung cancer in the Korean population. 相似文献
994.
Jin Hee Jung Jeong Ok Lee Ji Hae Kim Soo Kyung Lee Ga Young You Sun Hwa Park Ji Man Park Eung‐Kyun Kim Pann‐Ghill Suh Jin Kyung An Hyeon Soo Kim 《Journal of cellular physiology》2010,223(2):408-414
Quercetin, an anti‐oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells, although the mechanism is not completely understood. In this study, we found that quercetin increased the phosphorylation of AMP‐activated protein kinase (AMPK) and downstream acetyl‐CoA carboxylase (ACC) and suppressed the viability of HeLa cells. AICAR, an AMPK activator, and quercetin down‐regulated heat shock protein (HSP)70 and increased the activity of the pro‐apoptotic effector, caspase 3. Knock‐down of AMPK blocked quercetin‐mediated HSP70 down‐regulation. Moreover, knock‐down of HSP70 enhanced quercetin‐mediated caspase 3 activation. Furthermore, quercetin sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases, PP2a and SHP‐2. Finally, quercetin increased the interaction between EGFR and Cbl, and also induced the tyrosine phosphorylation of Cbl. Together, these results suggest that quercetin may have anti‐tumor effects on HeLa cells via AMPK‐induced HSP70 and down‐regulation of EGFR. J. Cell. Physiol. 223: 408–414, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
995.
Sang Hwa Kim Naval P. Shanware Michael J. Bowler Randal S. Tibbetts 《The Journal of biological chemistry》2010,285(44):34097-34105
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that preferentially targets motor neurons. It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA-binding domain protein) and FUS/TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS. The convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations are suggestive of a functional relationship; however, whether or not TDP-43 and FUS/TLS operate in common biochemical pathways is not known. Here we show that TDP-43 and FUS/TLS directly interact to form a complex at endogenous expression levels in mammalian cells. Binding was mediated by an unstructured TDP-43 C-terminal domain and occurred within the context of a 300–400-kDa complex that also contained C-terminal cleavage products of TDP-43 linked to neuropathology. TDP-43 C-terminal fragments were excluded from large molecular mass TDP-43 ribonucleoprotein complexes but retained FUS/TLS binding activity. The functional significance of TDP-43-FUS/TLS complexes was established by showing that RNAi silencing of either TDP-43 or FUS/TLS reduced the expression of histone deacetylase (HDAC) 6 mRNA. TDP-43 and FUS/TLS associated with HDAC6 mRNA in intact cells and in vitro, and competition experiments suggested that the proteins occupy overlapping binding sites. The combined findings demonstrate that TDP-43 and FUS/TLS form a functional complex in intact cells and suggest that convergent ALS phenotypes associated with TDP-43 and FUS/TLS mutations may reflect their participation in common biochemical processes. 相似文献
996.
Glutamine synthetase (GS) is the central enzyme for nitrogen assimilation in Escherichia coli and is subject to reversible adenylylation (inactivation) by a bifunctional GS adenylyltransferase/adenylyl-removing enzyme (ATase). In vitro, both of the opposing activities of ATase are regulated by small effectors, most notably glutamine and 2-oxoglutarate. In vivo, adenylyltransferase (AT) activity is critical for growth adaptation when cells are shifted from nitrogen-limiting to nitrogen-excess conditions and a rapid decrease of GS activity by adenylylation is needed. Here, we show that the adenylyl-removing (AR) activity of ATase is required to counterbalance its AT activity during steady-state growth under both nitrogen-excess and nitrogen-limiting conditions. This conclusion was established by studying AR−/AT+ mutants, which surprisingly displayed steady-state growth defects in nitrogen-excess conditions due to excessive GS adenylylation. Moreover, GS was abnormally adenylylated in the AR− mutants even under nitrogen-limiting conditions, whereas there was little GS adenylylation in wild-type strains. Despite the importance of AR activity, we establish that AT activity is significantly regulated in vivo, mainly by the cellular glutamine concentration. There is good general agreement between quantitative estimates of AT regulation in vivo and results derived from previous in vitro studies except at very low AT activities. We propose additional mechanisms for the low AT activities in vivo. The results suggest that dynamic counterbalance by reversible covalent modification may be a general strategy for controlling the activity of enzymes such as GS, whose physiological output allows adaptation to environmental fluctuations. 相似文献
997.
Cho KS Park SH Joo SH Kim SH Shin CY 《Biochemical and biophysical research communications》2010,394(1):48-53
There is strong clinical evidence that implicates tenofovir in the loss of bone mineral density during treatment of human immunodeficiency virus infection. In this study, we sought to test the hypothesis that tenofovir treatment of osteoblasts causes changes in the gene expression profile that would impact osteoblast function during bone formation. Primary osteoblasts were isolated and then treated with the tenofovir prodrug, tenofovir disoproxil fumarate (TDF). Total RNA from TDF-treated and untreated osteoblasts were extracted and used for microarray analysis to assess TDF-associated changes in the gene expression profile. Strikingly, the changes in gene expression profiles involved in cell signaling, cell cycle and amino acid metabolism, which would likely impact osteoblast function in bone formation. Our findings demonstrate for the first time that tenofovir treatment of primary osteoblasts results in gene expression changes that implicate loss of osteoblast function in tenofovir-associated bone mineral density loss. 相似文献
998.
Kim KY Kim HY Kim JH Lee CH Kim DH Lee YH Han SH Lim JS Cho DH Lee MS Yoon S Kim KI Yoon DY Yang Y 《FEBS letters》2006,580(16):3953-3960
CTRP1, a member of the CTRP superfamily, consists of an N-terminal signal peptide sequence followed by a variable region, a collagen repeat domain, and a C-terminal globular domain. CTRP1 is expressed at high levels in adipose tissues of LPS-stimulated Sprague-Dawley rats. The LPS-induced increase in CTRP1 gene expression was found to be mediated by TNF-alpha and IL-1beta. Also, a high level of expression of CTRP1 mRNA was observed in adipose tissues of Zucker diabetic fatty (fa/fa) rats, compared to Sprague-Dawley rats in the absence of LPS stimulation. These findings indicate that CTRP1 expression may be associated with a low-grade chronic inflammation status in adipose tissues. 相似文献
999.
Choi SH Kim SY An JJ Lee SH Kim DW Ryu HJ Lee NI Yeo SI Jang SH Won MH Kang TC Kwon HJ Cho SW Kim J Lee KS Park J Eum WS Choi SY 《FEBS letters》2006,580(30):6755-6762
The consequences of ultraviolet (UV) exposure are implicated in skin aging and cell death. The ribosomal protein S3 (rpS3) is one of the major proteins by which cells counteract the deleterious effects of UV and it plays a role in the repair of damaged DNA. In the present study, we investigated the protective effects of PEP-1-rpS3 fusion protein after UV-induced cell injury. A human rpS3 gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-rpS3 fusion protein. The expressed and purified fusion proteins were efficiently transduced into skin cells in a time- and dose-dependent manner. Once inside the cells, transduced PEP-1-rpS3 fusion protein was stable for 48 h. We showed that transduced PEP-1-rpS3 fusion protein increased cell viability and dramatically reduced DNA lesions in the UV exposed skin cells. Immunohistochemical analysis revealed that PEP-1-rpS3 fusion protein efficiently penetrated the epidermis as well as the dermis of the subcutaneous layer when sprayed on animal skin. These results suggest that PEP-1-rpS3 fusion protein can be used in protein therapy for various disorders related to UV, including skin aging and cancer. 相似文献
1000.
Primary rat hepatocytes were cryopreserved in hormonally-defined medium (HDM) containing 40% (v/v) fetal bovine serum (FBS)
and 10% (v/v) dimethyl sulfoxide (DMSO) in liquid N2 for 6 months. After thawing, the cells were immobilized using 2% (w/v) alginate and 0.5% (w/v) chitosan solutions. The capacities
of ammonia removal and urea synthesis of the immobilized-thawed hepatocytes were similar to those of immobilized hepatocytes
without cryopreservation. This result shows that immobilized hepatocytes after cryopreservation are useful for the development
of a bioartificial liver system. 相似文献