• Molecules and Cells
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• v.45 no.7
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• pp.454-464
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• 2022

DJ-1 is one of the causative genes of early-onset familial Parkinson's disease (PD). As a result, DJ-1 influences the pathogenesis of sporadic PD. DJ-1 has various physiological functions that converge to control the levels of intracellular reactive oxygen species (ROS). Based on genetic analyses that sought to investigate novel antioxidant DJ-1 downstream genes, pyruvate dehydrogenase (PDH) kinase (PDK) was demonstrated to increase survival rates and decrease dopaminergic (DA) neuron loss in DJ-1 mutant flies under oxidative stress. PDK phosphorylates and inhibits the PDH complex (PDC), subsequently downregulating glucose metabolism in the mitochondria, which is a major source of intracellular ROS. A loss-of-function mutation in PDK was not found to have a significant effect on fly development and reproduction, but severely ameliorated oxidative stress resistance. Thus, PDK plays a critical role in the protection against oxidative stress. Loss of PDH phosphatase (PDP), which dephosphorylates and activates PDH, was also shown to protect DJ-1 mutants from oxidative stress, ultimately supporting our findings. Further genetic analyses suggested that DJ-1 controls PDK expression through hypoxia-inducible factor 1 (HIF-1), a transcriptional regulator of the adaptive response to hypoxia and oxidative stress. Furthermore, CPI-613, an inhibitor of PDH, protected DJ-1 null flies from oxidative stress, suggesting that the genetic and pharmacological inhibition of PDH may be a novel treatment strategy for PD associated with DJ-1 dysfunction.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.113-113
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• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• Journal of Life Science
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• v.34 no.1
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• pp.37-47
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• 2024

FUN14 domain-containing protein 1 (FUNDC1), an outer mitochondrial membrane protein, contributes to removal of damaged mitochondria through mitophagy. In this study, to elucidate the role of the FUNDC1 in the amyloid beta peptide (A_β)-induced neuropathy, changes in the degree of mitochondrial dysfunction and cell injury caused by A_β treatment were examined in the HT-22 neuronal cells in which the FUNDC1 expression was transiently silenced or overexpressed. We found that A_β treatment causes a time-dependent decrease of the FUNDC1 expression. In the A_β-treated cells, there were a drop in MTT reduction ability, depletion of cellular ATP, disruption of mitochondrial membrane potential, stimulation of cellular ROS production, and increased mitochondrial Ca²⁺ load. Activation of caspase-3 and induction of apoptotic cell death were also observed. Transient silencing of the FUNDC1 expression by transfection with the FUNDC1 small interfering RNA per se caused mitochondrial dysfunction and apoptotic cell death like the effect of A_β treatment. Conversely, in cells in which the FUNDC1 was transiently overexpressed by FUNDC1-Myc transfection, overexpression itself had no effect on the mitochondrial functional integrity and cell survival but showed a significant prevention effect against mitochondrial and cell injury caused by A_β treatment. Overall, these results suggest that the FUNDC1 is importantly involved in the A_β-induced mitochondrial dysfunction and cell injury in the HT-22 neuronal cells.

• Communications of the Korean Mathematical Society
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• v.32 no.1
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• pp.193-200
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• 2017

Given a pair p, q of relative prime positive integers, we have uniquely determined positive integers x, y, u and v such that vx-uy = 1, p = x + y and q = u + v. Using this property, we show that$${\sum\limits_{1{\leq}i{\leq}x,1{\leq}j{\leq}v}}\;{t^{(i-1)q+(j-1)p}\;-\;{\sum\limits_{1{\leq}k{\leq}y,1{\leq}l{\leq}u}}\;t^{1+(k-1)q+(l-1)p}$$ is the Alexander polynomial ${\Delta}_{p,q}(t)$ of a torus knot t(p, q). Hence the number $N_{p,q}$ of non-zero terms of ${\Delta}_{p,q}(t)$ is equal to vx + uy = 2vx - 1. Owing to well known results in knot Floer homology theory, our expanding formula of the Alexander polynomial of a torus knot provides a method of algorithmically determining the total rank of its knot Floer homology or equivalently the complexity of its (1,1)-diagram. In particular we prove (see Corollary 2.8); Let q be a positive integer> 1 and let k be a positive integer. Then we have $$\begin{array}{rccl}(1)&N_{kq}+1,q&=&2k(q-1)+1\\(2)&N_{kq}+q-1,q&=&2(k+1)(q-1)-1\\(3)&N_{kq}+2,q&=&{\frac{1}{2}}k(q^2-1)+q\\(4)&N_{kq}+q-2,q&=&{\frac{1}{2}}(k+1)(q^2-1)-q\end{array}$$ where we further assume q is odd in formula (3) and (4). Consequently we confirm that the complexities of (1,1)-diagrams of torus knots of type t(kq + 2, q) and t(kq + q - 2, q) in [5] agree with $N_{kq+2,q}$ and $N_{kq+q-2,q}$ respectively.

• Pediatric Infection and Vaccine
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• v.18 no.2
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• pp.173-181
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• 2011

Purpose : 2009 Pandemic influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. We described the clinical and epidemiological characteristics of H1N1 influenza infection. Methods : We used retrospective medical chart reviews to collect data on the visiting patients from a single institute. H1N1 infection was confirmed in specimens with the use of a RT-PCR (real time reverse transcriptase polymerase chain reaction assay). Result : 6,836 patients had H1N1 RT-PCR test, and 2,781 were confirmed with H1N1 virus infection. 158 patients (5.7%) had hospital treatment and inpatients were significantly younger (5.4${\pm}$3.3 years) than outpatients (7.5${\pm}$3.9 years) among H1N1 virus confirmed patients. Oxygen, steroid, immunoglobulin, ventilator treatment was provided in a substantial proportion among pneumonia patients accompanying wheezy respiration. In addition more intensive care was needed in patients accompanying segmental, lobar, interstitial, mixed pneumonia and lung effusion (27.2%) than patients with bronchopneumonia (7.3%) among H1N1 virus infection confirmed patients. Seventy-one infants had oseltamivir treatment out of 83 infants under 1 year, and no significant side effects and complications were identified. Conclusion : In 2009 pandemic influenza A (H1N1), hospital treatment was needed in younger patients. Early intensive care was needed in pneumonia patients accompanying wheezy respiration, and patients accompanying segmental, lobar, interstitial, mixed pneumonia and lung effusion.

• Bulletin of the Korean Mathematical Society
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• v.47 no.3
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• pp.645-651
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• 2010

In this note we study positive solutions of the mth order rational difference equation $x_n=(a_0+\sum{{m\atop{i=1}}a_ix_{n-i}/(b_0+\sum{{m\atop{i=1}}b_ix_{n-i}$, where n = m,m+1,m+2, $\ldots$ and $x_0,\ldots,x_{m-1}$ > 0. We describe a sufficient condition on nonnegative real numbers $a_0,a_1,\ldots,a_m,b_0,b_1,\ldots,b_m$ under which every solution $x_n$ of the above equation tends to the limit $(A-b_0+\sqrt{(A-b_0)^2+4_{a_0}B}$/2B as $n{\rightarrow}{\infty}$, where $A=\sum{{m\atop{i=1}}\;a_i$ and $B=\sum{{m\atop{i=1}}\;b_i$.

• Archives of Pharmacal Research
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• v.8 no.3
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• pp.109-117
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• 1985

The interaction of salicylic acid (S. A.), salicylamide (S,M) with nucleic acid base derivatives such as 9-ethyl adenine (A), 1-cyclohexyl uracil (U), 2', 3'-benzylidine-5' trityl-cytidine (C), gaunosine-2', 3', 5'-isobutylate (G) has been spectroscopically investigated to determine the binding mechanism. NMR and IR spectra were measured in nonpolar solvents. The association constant K of the formation of complex was calculated from the IR spectra. Compounds S. A. and A form a 1:1 or 1:2 cyclic hydrogen-bonded complex depending on the sample concentration. Compounds S. A. and U form a 1:1 or 1:2 hydrogen-bonded complex on the sample concentration. Compounds S. A. and C form a 2:1 hydrogen-bonded complex at low concentration (0.0016M). Compound S. A. binds compound G, but its binding does not completely break the self-association of compound G, Compound S. M. binds compounds A. U. C. G. very weakly.

• The Pure and Applied Mathematics
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• v.29 no.1
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• pp.59-68
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• 2022

For a finite group G ⊂ GL(n, ℂ), the G-Hilbert scheme is a fine moduli space of G-clusters, which are 0-dimensional G-invariant subschemes Z with H⁰(𝒪_Z ) isomorphic to ℂ[G]. In many cases, the G-Hilbert scheme provides a good resolution of the quotient singularity ℂⁿ/G, but in general it can be very singular. In this note, we prove that for a cyclic group A ⊂ GL(n, ℂ) of type ${\frac{1}{r}}$(1, …, 1, a) with r coprime to a, A-Hilbert Scheme is smooth and irreducible.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.895-903
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• 2005

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated under pathological conditions or by extracellular stimuli, and the regulation of TSP-1 gene expression is important for developing new approaches in tumor therapy. Mistletoe is a parasitir plant that have been used for immunomodulation and antitumor therapy. Helixor A is an aqueous part of mistletoes extract. Here we showed that TSP-1 expression was significantly induced at both mRNA and protein levels in the Hepatocarcinorna cell line (Hep3B) and primary bovine endothelial cell line (BAE) exposed to Helixor A. Our promoter analysis confirmed that the expression of TSP-1 gene was regulated by Helixor A at the transcriptional level. In cell invasion assay, the conditioned media obtained from treatment of these cells significantly reduced the number of invasive cells and also inhibited capillary-like tube formation of BAE cells on Matrigel. Moreover, the inhibitory efforts of the conditioned media on cell invasion and tube formation were reversed by blocking with anti-TSP-1 neutralizing antibodies, suggesting that TSP-1 is involved in Helixor A-indured antiangiogenic effect. Taken together, our results suggest that Helixor A have an antiangiogenic effects through upregulation of TSP-1.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1757-1760
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• 2012

Breast cancer is a major cause of death in women worldwide. Mammary tissue expressing xenobiotic metabolizing enzymes metabolically activate or detoxify potential genotoxic breast carcinogens. Deregulation of these xenobiotic metabolizing enzymes is considered to be a major contributory factor to breast cancer. The present study is focused on the expression of the xenobiotic metabolizing gene, CYP1A1, in breast cancer and its possible relationships with different risk factors. Twenty five tumors and twenty five control breast tissue samples were collected from patients undergoing planned surgery or biopsy from different hospitals. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western-blotting were used to investigate the expression of CYP1A1 in breast cancer control and disease samples. mRNA expression of CYP1A1 was down-regulated in 40% of breast tumor samples. Down-regulation was also observed at the protein level. Significnat relations were noted with marital status and tumour grade but not histopathological type. In conclusion, CYP1A1 protein expression was markedly reduced in tumor breast tissues samples as compared to paired control tissue samples.