• 제목/요약/키워드: down-regulation

검색결과 1,254건 처리시간 0.022초

Changes of Gene Expression in NIH3T3 Cells Exposed to Osmotic and Oxidative Stresses

  • Lee, Jae-Seon;Jung, Ji-Hun;Kim, Tae-Hyung;Seo, Jeong-Sun
    • Genomics & Informatics
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    • 제2권2호
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    • pp.67-74
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    • 2004
  • Cells consistently face stressful conditions, which cause them to modulate a variety of intracellular processes and adapt to these environmental changes via regulation of gene expression. Hyperosmotic and oxidative stresses are significant stressors that induce cellular damage, and finally cell death. In this study, oligonucleotide microarrays were employed to investigate mRNA level changes in cells exposed to hyperosmotic or oxidative conditions. In addition, since heat shock protein 70 (HSP70) is one of the most inducible stress proteins and plays pivotal role to protect cells against stressful condition, we performed microarray analysis in HSP70-overexpressing cells to identify the genes expressed in a HSP70-dependent manner. Under hyperosmotic or oxidative stress conditions, a variety of genes showed altered expression. Down­regulation of protein phosphatase1 beta (PP1 beta) and sphingosine-1-phosphate phosphatase 1 (SPPase1) was detected in both stress conditions. Microarray analysis of HSP70-overexpressing cells demonstrated that diverse mRNA species depend on the level of cellular HSP70. Genes encoding Iysyl oxidase, thrombospondin 1, and procollagen displayed altered expression in all tested conditions. The results of this study will be useful to construct networks of stress response genes.

Human Liver Specific Transcriptional Factor TCP10L Binds to MAD4

  • Jiang, Dao-Jun;Yu, Hong-Xiu;Hexige, Sa-Yin;Guo, Ze-Kun;Wang, Xiang;Ma, Li-Jie;Chen, Zheng;Zhao, Shou-Yuan;Yu, Long
    • BMB Reports
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    • 제37권4호
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    • pp.402-407
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    • 2004
  • A human gene T-complex protein 10 like (TCP10L) was cloned in our lab. A previous study showed that it expressed specifically in the liver and testis. A transcription experiment revealed that TCP10L was a transcription factor with transcription inhibition activity. In this study, the human MAD4 was identified to interact with TCP10L by a yeast two-hybrid screen. This finding was confirmed by immunoprecipitation and subcellular localization experiments. As MAD4 is a member of the MAD family, which antagonizes the functions of MYC and promotes cell differentiation, the biological function of the interaction between TCP10L and MAD4 may be to maintain the differentiation state in liver cells. Also, we propose that the up-regulation of Myc is caused by the down-regulation of TCP10L in human hepatocarcinomas.

Regulation of melanocyte apoptosis by Stathmin 1 expression

  • Zhang, Yan;Xiong, Jianjun;Wang, Jiali;Shi, Xianping;Bao, Guodong;Zhang, Yang;Zhu, Zhenyu
    • BMB Reports
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    • 제41권11호
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    • pp.765-770
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    • 2008
  • Undesirable hyperpigmentation that can arise from increased melanocyte activity may be alleviated by targeting active melanocytes for apoptosis. The role of Stathmin 1 as an important regulator of microtubule dynamics is well documented. The current study examined the potential of Stathmin 1-targeting strategies in eliminating active melanocytes. A vector to overexpress Stathmin 1 and vectors to express three distinct small hairpin RNAs to knockdown Stathmin 1 expression in normal melanocytes were produced and in cell cultures acted accordingly. Both overexpression and knockdown of Stathmin 1 led to a marked increase in melanocyte apoptosis, as indicated by the accumulation of apoptotic cells and increased levels of cleaved caspase-3. Both up- and down-regulation of Stathmin 1 expression inhibited the activity of differentiated melanocytes, as indicated by decreases in both melanin production and tyrosinase activity. Taken together, these results indicate that hyperactive melanocytes can be inhibited by altering Stathmin 1 expression.

Raf 신호에 의한 초파리 fascin의 조절 (Regulation of the Drosophila Fascin by Raf Signaling)

  • 표정훈;최나현;이신해;김영신;유미애
    • 생명과학회지
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    • 제19권7호
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    • pp.866-870
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    • 2009
  • Fascin은 액틴결합 단백질로 형성을 포함한 많은 발생과정에 있어서 중요한 역할을 한다. Fascin은 암세포에 대한 생체표지인자로도 잘 알려져 있다. 그러나 이러한 fascin 유전자의 발현조절기전은 현재까지 잘 알려져있다. 그러나 이러한 fascin 유전자의 발현조절기전은 현재까지 잘 알려져 있지 않다. 본 연구에서는 Raf 돌연변이 초파리에서 이미 보고 되어있는 초파리 fascin 돌연변이 초파리의 휘어진 등털 표현형을 관찰함으로써 초파리 fascin 유전자의 발현이 Raf신호체계에 의해 조절되는 가를 조사하였다. RT-PCR과 Western blot의 실험 방법으로 Raf 유전자 돌연변이 초파리에서 fascin의 발현이 감소되어 있는 것을 확인하였으며, GAL4-UAS계로 Raf를 과발현시킨 초파리에서 fascin 발현이 증가하는 것을 확인할 수 있었다. 또한 세포의 증식과 이동 연구모델계로 잘 알려져 있는 초파리의 혈액세포에서 이러한 조절기전을 확인하였다. 이러한 결과들은 fascin유전자의 발현이 Raf 신호체계에 의해 조절된다는 것을 나타낸다.

중추신경계 손상 회복에 미치는 대한 조구등의 영향 (The Effect of the Uncariae Ramulus et Uncus on the Regeneration Following CNS Injury)

  • 이진구;박형진;김동웅;송봉근
    • 대한약침학회지
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    • 제12권1호
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    • pp.67-76
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    • 2009
  • Objective : Following central nervous system(CNS) injury, inhibitory influences at the site of axonal damage occur. Glial cells become reactive and form a glial scar, gliosis. Also myelin debris such as MAG inhibits axonal regeneration. Astrocyte-rich gliosis relates with up-regulation of GFAP and CD81, and eventually becomes physical and mechanical barrier to axonal regeneration. MAG is one of several endogenous axon regeneration inhibitors that limit recovery from CNS injury and disease. It was reported that molecules that block such inhibitors enhanced axon regeneration and functional recovery. Recently it was reported that treatment with anti-CD81 antibodies enhanced functional recovery in the rat with spinal cord injury. So in this current study, the author investigated the effect of the water extract of Uncariae Ramulus et Uncus on the regulation of CD81, GFAP and MAG that increase when gliosis occurs. Methods : MTT assay was performed to examine cell viability, and cell-based ELISA, western blot and PCR were used to detect the expression of CD81, GFAP and MAG. Then also immunohistochemistry was performed to confirm in vivo. Results : Water extract of Uncariae Ramulus et Uncus showed relatively high cell viability at the concentration of 0.05%, 0.1% and 0.5%. The expression of CD81, GFAP and MAG in astrocytes was decreased after the administration of Uncariae Ramulus et Uncus water extract. These results was confirmed in the brain sections following cortical stab injury by immunohistochemistry. Conclusion : The authors observed that Uncariae Ramulus et Uncus significantly down-regulates the expression of CD81, GFAP and MAG. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

Gonadotropins Improve Porcine Oocyte Maturation and Embryo Development through Regulation of Maternal Gene Expression

  • Wang, Qing-Ling;Zhao, Ming-Hui;Jin, Yong-Xun;Kim, Nam-Hyung;Cui, Xiang-Shun
    • 한국수정란이식학회지
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    • 제28권4호
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    • pp.361-371
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    • 2013
  • The present study assessed the effect of FSH and LH on oocyte meiotic, cytoplasmic maturation and on the expression level and polyadenylation status of several maternal genes. Cumulus-oocyte complexes were cultured in the presence of FSH, LH, or the combination of FSH and LH. Significant cumulus expansion and nuclear maturation was observed upon exposure to FSH alone and to the combination of FSH and LH. The combination of FSH and LH during entire IVM increased the mRNA level of four maternal genes, C-mos, Cyclin B1, Gdf9 and Bmp15, at 28 h. Supplemented with FSH or LH significantly enhanced the polyadenylation of Gdf9 and Bmp15; and altered the expression level of Gdf9 and Bmp15. Following parthenogenesis, the exposure of oocytes to combination of FSH and LH during IVM significantly increased cleavage rate, blastocyst formation rate and total cell number, and decreased apoptosis. In addition, FSH and LH down-regulated the autophagy gene Atg6 and upregulated the apoptosis gene Bcl-xL at the mRNA level in blastocysts. These data suggest that the FSH and LH enhance meiotic and cytoplasmic maturation, possibly through the regulation of maternal gene expression and polyadenylation. Overall, we show here that FSH and LH inhibit apoptosis and autophagy and improve parthenogenetic embryo competence and development.

Exposure to 835 MHz RF-EMF decreases the expression of calcium channels, inhibits apoptosis, but induces autophagy in the mouse hippocampus

  • Kim, Ju Hwan;Sohn, Uy Dong;Kim, Hyung-Gun;Kim, Hak Rim
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권3호
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    • pp.277-289
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    • 2018
  • The exponential increase in the use of mobile communication has triggered public concerns about the potential adverse effects of radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones on the central nervous system (CNS). In this study, we explored the relationship between calcium channels and apoptosis or autophagy in the hippocampus of C57BL/6 mice after RF-EMF exposure with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Firstly, the expression level of voltage-gated calcium channels (VGCCs), a key regulator of the entry of calcium ions into the cell, was confirmed by immunoblots. We investigated and confirmed that pan-calcium channel expression in hippocampal neurons were significantly decreased after exposure to RF-EMF. With the observed accumulation of autolysosomes in hippocampal neurons via TEM, the expressions of autophagy-related genes and proteins (e.g., LC3B-II) had significantly increased. However, down-regulation of the apoptotic pathway may contribute to the decrease in calcium channel expression, and thus lower levels of calcium in hippocampal neurons. These results suggested that exposure of RF-EMF could alter intracellular calcium homeostasis by decreasing calcium channel expression in the hippocampus; presumably by activating the autophagy pathway, while inhibiting apoptotic regulation as an adaptation process for 835 MHz RF-EMF exposure.

LED Driver with TRIAC Dimming Control by Variable Switched Capacitance for Power Regulation

  • Lee, Eun-Soo;Sohn, Yeung-Hoon;Nguyen, Duy Tan;Cheon, Jun-Pil;Rim, Chun-Taek
    • Journal of Power Electronics
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    • 제15권2호
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    • pp.555-566
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    • 2015
  • A TRIAC dimming LED driver that can control the brightness of LED arrays for a wide range of source voltage variations is proposed in this paper. Unlike conventional PWM LED drivers, the proposed LED driver adopts a TRIAC switch, which inherently guarantees zero current switching and has been proven to be quite reliable over its long lifetime. Unlike previous TRIAC type LED drivers, the proposed LED driver is composed of an LC input filter and a variable switched capacitance, which is modulated by the TRIAC turn-on timing. Thus, the LED power regulation and dimming control, which are done by a volume resistor in the same way as the conventional TRIAC dimmers, can be simultaneously performed by the TRIAC control circuit. Because the proposed LED driver has high efficiency and a long lifetime with a high power factor (PF) and low total harmonic distortion (THD) characteristics, it is quite adequate for industrial lighting applications such as streets, factories, parking garages, and emergency stairs. A simple step-down capacitive power supply circuit composed of passive components only is also proposed, which is quite useful for providing DC power from an AC source without a bulky and heavy transformer. A prototype 60 W LED driver was implemented by the proposed design procedure and verified by simulation and experimental results, where the efficiency, PF, and THD are 92%, 0.94, and 6.3%, respectively. The LED power variation is well mitigated to below ${\pm}2%$ for 190 V < $V_s$ < 250 V by using the proposed simple control circuit.

1-methyl-4-phenylpyridinium($MPP^+$)로 유도된 파킨슨병의 세포손상에 대한 황백의 신경세포 보호효과 (Neuroprotective Effect of Methanol Extract of Phellodendri Cortex Against 1-methyl-4-Phenylpyridinium-induced Apoptosis in PC-12 Cells)

  • 정영석;정혜미;서운교
    • 대한한방내과학회지
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    • 제30권1호
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    • pp.51-63
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    • 2009
  • Background and Objective : The prospects for developing an anti-apoptotic natural component or a compound that exerts a neuroprotective effect with few or no side effects for the treatment of neurodegenerative disease appear favorable. In the present study, we evaluated the effects of the methanol extract of Phellodendri Cortex (PC extract) on 1-methyl-4-phenyl pyridinium($MPP^+$)-induced apoptosis in PC-12 cells. Materials and Methods : We used the methanol extract of Phellodendri Cortex (PC extract). PC-12 cells were cultured by RPMZ-1640. We found the PC extract's gene expression (Bax, Bcl-2) by using RT-PCR. We examined the PC extract's protein expression (Bcl-2, Bax, cytochrome c, poly (ADP-ribose) polymerase (PARP), caspase-3) by SDS-PAGE and Western blot. Results : Apoptosis in $MPP^+$-induced PC-12 cells was accompanied by an increased Bax/Bcl-2 ratio, release of cytochrome c to the cytosol and the activation of caspase-3. PC extract inhibited the down-regulation of Bcl-2 and the up-regulation of Bax, as well as the release of mitochondrial cytochrome c into the cytosol. In addition, PC extract attenuated caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP). Conclusion : These results suggest that the neuroprotective potentials of PC extract against $MPP^+$-induced apoptosis can be. at least partially, ascribed to its anti-apoptotic effects in PC-12 cells.

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인간 신경모세포종 세포주 LAN5에 대한 부정항암탕(扶正抗癌湯)의 항종양효과 (Anti-cancer Effects of Bujeonghangam-tang on Human Neuroblastoma Cell Line LAN5)

  • 조영기;이성균;이정섭;남상규;정현애;문구;문미현
    • 동의생리병리학회지
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    • 제20권6호
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    • pp.1548-1555
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    • 2006
  • Bujeonghangam-tang(BHT) has been used as an anticancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. To investigate cell death mechanism by BHT in cancer cells, the activities of apoptosis signaling pathway were tested in human neuroblastoma cell line LAN5. Viability of LAN5 cells was markedly decreased by treatment of the water extract of BHT in a dose-dependent manner. BHT induced cell death was confirmed as apoptosis characterized by chromatin condensation. We tested whether the water extract of BHT affects the anti-apoptotic protein such as Bcl-2 and Bcl-XL, and the pro-apoptotic protein such as Bax. Both Bcl-2 and Bcl-XL were gradually decreased but Bas was increased in a time-dependent manner after the addition of the water extract of BHT. Cleavage of Bid by activation of caspase-8 protease was also observed in LAN-5 cells by the treatment of the water extract of BHT. Taken together, these results suggest that the water extract of BHT exerts anti-cancer effects on human neuroblastoma LAN-5 cells by inducing the apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl-2 and Bcl-XL, up-regulation of pro-apoptotic protein such as Bax, and activation of intrinsic caspase cascades.