Biomedical subjects

Dae Young Jung

Publications and source records attributed to Dae Young Jung.

4 recordsLinked to original sources

PubMed2006

Profiling of differentially expressed genes in human stem cells by cDNA microarray.

Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation, although a wide variety of adult stem cells as well as embryonic stem cells have been identified and stem cell plasticity has recently been reported. To identify genes implicated in the control of the stem cell state as well as the characteristics of each stem cell line, we analyzed the expression profiles of genes in human embryonic, hematopoietic (CD34+ and CD133+), and mesenchymal stem cells using cDNA microarrays, and identified genes that were differentially expressed in specific stem cell populations. In particular we were able to identify potential hESC signature-like genes that encode transcription factors (TFAP2C and MYCN), an RNA binding protein (IMP-3), and a functionally uncharacterized protein (MAGEA4). The overlapping sets of 22 up-regulated and 141 down-regulated genes identified in this study of three human stem cell types may also provide insight into the developmental mechanisms common to all human stem cells. Furthermore, our comprehensive analyses of gene expression profiles in various adult stem cells may help to identify the genetic pathways involved in self-renewal as well as in multi-lineage specific differentiation.

Adult↗

PubMed2005

Sequential induction of heme oxygenase-1 and manganese superoxide dismutase protects cultured astrocytes against nitric oxide.

Nitric oxide (NO) is a widely recognized mediator of physiological and pathophysiological signal transmission. In an attempt to better understand the molecular actions of NO in astrocytes, stress protein expression in response to NO donor sodium nitroprusside was investigated. Heme oxygenase-1 (HO-1) has been identified as an inducer of manganese superoxide dismutase (MnSOD), playing a cytoprotective role under the condition of nitrosative stress. We present evidence that the sequential induction of HO-1 and MnSOD protects astrocytes from NO toxicity: (1) both HO-1 and MnSOD expression were induced by NO; (2) NO-mediated increase in MnSOD activity was partly abolished by HO-1 inhibitor Zn(II) protoporphyrin IX (ZnPP); (3) pretreatment of astrocytes with a nontoxic dose of NO protected the cells against the later treatment with a toxic dose of NO; (4) inhibition of HO-1 by ZnPP sensitized astrocytes to the nontoxic dose of NO resulting in a marked cytotoxicity; and (5) adenovirus-mediated overexpression of MnSOD protected astrocytes from the NO toxicity. The molecular action of NO in astrocytes appears to be dose-dependent. While a high dose of NO exerts cytotoxicity leading to the tissue damage in the central nervous system, a low dose of NO may act as an important signaling molecule in astrocytes with concurrent induction of cytoprotective proteins such as HO-1 and MnSOD.

Animals↗

PubMed2005

TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker.

TLRs mediate diverse signaling after recognition of evolutionary conserved pathogen-associated molecular patterns such as LPS and lipopeptides. Both TLR2 and TLR4 are known to trigger a protective immune response as well as cellular apoptosis. In this study, we present evidence that TLR4, but not TLR2, mediates an autoregulatory apoptosis of activated microglia. Brain microglia underwent apoptosis upon stimulation with TLR4 ligand (LPS), but not TLR2 ligands (Pam(3)Cys-Ser-Lys(4), peptidoglycan, and lipoteichoic acid). Based on studies using TLR2-deficient or TLR4 mutant mice and TLR dominant-negative mutants, we also demonstrated that TLR4, but not TLR2, is necessary for microglial apoptosis. The critical difference between TLR2 and TLR4 signalings in microglia was IFN regulatory factor-3 (IRF-3) activation, followed by IFN-beta expression: while TLR4 agonist induced the activation of IRF-3/IFN-beta pathway, TLR2 did not. Nevertheless, both TLR2 and TLR4 agonists strongly induced NF-kappaB activation and NO production in microglia. Neutralizing Ab against IFN-beta attenuated TLR4-mediated microglial apoptosis. IFN-beta alone, however, did not induce a significant cell death. Meanwhile, TLR2 activation induced microglial apoptosis with help of IFN-beta, indicating that IFN-beta production following IRF-3 activation determines the apoptogenic action of TLR signaling. TLR4-mediated microglial apoptosis was mediated by MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-beta, and was associated with caspase-11 and -3 activation rather than Fas-associated death domain protein/caspase-8 pathway. Taken together, TLR4 appears to signal a microglial apoptosis via autocrine/paracrine IFN-beta production, which may act as an apoptotic sensitizer.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Pro-apoptotic activity of N-myc in activation-induced cell death of microglia.

Brain microglial cells are thought to undergo apoptosis following the exposure to inflammatory stimuli such as lipopolysaccharide (LPS) and IFNgamma, which is considered as an autoregulatory mechanism to control their own activation state. Here, we report that N-myc constitutes a novel apoptotic pathway of LPS/IFNgamma-activated microglia. The expression of N-myc was synergistically enhanced by LPS and IFNgamma in microglia. Tetracycline-based conditional expression of N-myc sensitized microglia to nitric oxide (NO)-induced apoptosis. Knockdown of N-myc expression using small interfering RNA (siRNA) attenuated LPS/IFNgamma-induced microglial apoptosis. An increase in N-myc expression, however, did not affect microglial production of NO or TNFalpha. The synergistic effect of LPS/IFNgamma on the microglial N-myc induction was mediated through Janus kinase (JAK)/STAT1 (signal transducer and activator of transcription 1) pathway. Taken together, LPS/IFNgamma-induced N-myc participated in the activation-induced cell death of microglia by sensitizing the cells to NO-induced apoptosis; however, N-myc did not influence the processes of inflammatory activation of microglia.

Animals↗