Biomedical subjects

Jian-Hong Chen

Publications and source records attributed to Jian-Hong Chen.

6 recordsLinked to original sources

PubMed2006

Protective effects of transcription factor HESR1 on retinal vasculature.

HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch signaling pathway in vertebrate and Drosophila embryos, and is related to the HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial cells and could be an effector of Notch signaling in these cells. HESR1 is necessary for the induction of a tubular network and for continued maintenance of mature and quiescent blood vessels. To examine the role of HESR1 in retinal neovascularization, we transfected retinal vascular endothelial cells (HRCECs) with the HESR1 gene and studied its effects on the expression of angiogenic factors, on the proliferation and migration of endothelial cells, and on the formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated VEGFR-2 expression, upregulated occludin expression, inhibited the migration and proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a key role in the finely tuned network of molecules involved in the regulation of retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects of VEGF, shift endothelial cells from a proliferative state to a quiescent state, and restore normal vessel structures. Expression of the HESR1 gene in retinal vascular endothelial cells may protect retinal blood vessels and may be useful in the treatment of diseases involving damage to the retinal vasculature, including diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.

Adult↗

PubMed2006

Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells.

We recently found that formylpeptide receptor (FPR), a G-protein-coupled receptor that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine, is expressed by malignant human glioma cells and promotes tumor growth and angiogenesis. In this study, we examined the effect of Nordy, a novel chiral lipoxygenase inhibitor which was synthesized based on the structure of a natural nordihydroguaiaretic acid, on the expression of FPR by human glioblastoma cells. We found that FPR was expressed at the protein level by highly malignant human glioma cell lines U87 and BT325, and a rat glioma cell line C6. The expression level of FPR was correlated with the degree of the malignancy of tumor cells. The poorly differentiated glioma cell line U87 expressed the highest level of FPR. In U87 glioma cells, the expression of FPR was attenuated at the protein level by Nordy treatment for 48 (P<0.05). Nordy did not affect FPR mRNA expression in U87 cells. In addition, Nordy treatment seemed to promote glioma cell differentiation, as evidenced by their reduced expression of vimentin and increased expression of GFAP. Our results suggest that Nordy was capable of reducing the level of malignancy of glioma cells.

Animals↗

PubMed2006

Manganese modulates pro-inflammatory gene expression in activated glia.

Redox-active metals are of paramount importance for biological functions. Their impact and cellular activities participate in the physiological and pathophysiological processes of the central nervous system (CNS), including inflammatory responses. Manganese is an essential trace element and it is required for normal biological activities and ubiquitous enzymatic reactions. However, excessive chronic exposure to manganese results in neurobehavioral deficits. Recent evidence suggests that manganese neurotoxicity involves activation of microglia or astrocytes, representative CNS immune cells. In this study, we assessed the molecular basis of the effects of manganese on the modulation of pro-inflammatory cytokines and nitric oxide (NO) production in primary rat cortical glial cells. Cultured glial cells consisted of 85% of astrocytes and 15% of microglia. Within the assayed concentrations, manganese was unable to induce tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression, whereas it potentiated iNOS and TNF-alpha gene expression by lipopolysaccharide/interferon-gamma-activated glial cells. The enhancement was accompanied by elevation of free manganese, generation of oxidative stress, activation of mitogen-activated protein kinases, and increased NF-kappaB and AP-1 binding activities. The potentiated degradation of inhibitory molecule IkappaB-alpha was one of underlying mechanisms for the increased activation of NF-kappaB by manganese. However, manganese decreased iNOS enzymatic activity possibly through the depletion of cofactor since exogenous tetrahydrobiopterin reversed manganese's action. These data indicate that manganese could modulate glial inflammation through variable strategies.

Animals↗

PubMed2006

[A model for trans-translation].

Trans-translation is a mechanism that fixes stalled translation course. tmRNA is the core of trans-translation and it has dual function as a tRNA and a mRNA. tmRNA recognizes the ribosome carrying truncated mRNA with specificity under the help SmpB protein. It can be directed to A site by ribosomal protein S1. At first tmRNA prolongs the genetic message on the stalled mRNA, then termination codon stops peptide synthesis to form a nascent chain with the tag sequence. Finally, tmRNA-SmpB system frees stalled ribosomes and directs degradation of the products of these frustrated protein synthesis reactions. This paper introduces the most recent studies on trans-translation.

Escherichia coli↗

PubMed2005

Tyrosine kinase inhibitors attenuate Japanese encephalitis virus-induced neurotoxicity.

The cellular signaling molecules that underlie Japanese encephalitis virus (JEV)-induced inflammation and neurotoxicity are not well understood. We examined whether protein tyrosine kinase (PTK) inhibitors play roles in JEV replication and cytopathic effect in neuron/glia cultures. JEV infection caused significant neuronal injury. PTK inhibitors, genistein, herbimycin A, and PP2, attenuated JEV-induced neurotoxicity but failed to affect JEV replication. Infection of neuron/glia cultures with JEV produced elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). PTK inhibitors suppressed JEV-induced TNF-alpha and IL-1beta production at the transcriptional level. Neutralizing antibodies against TNF-alpha and IL-1beta partially suppressed JEV-induced neurotoxicity. JEV infection modulated tyrosine phosphorylation events within the course of infection. Currently, the nature of the affected phosphorylated proteins was not characterized. Our results suggest that PTKs, especially Src-related PTK, play roles in the production of TNF-alpha and IL-1beta during JEV infection and in the induction of neuronal death in neuron/glia cultures.

Animals↗

PubMed2004

Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection.

Infection with Japanese encephalitis virus (JEV) causes cerebral inflammation and stimulates inflammatory cytokine expression. Glial cells orchestrate immunocyte recruitment to focal sites of viral infection within the central nervous system (CNS) and synchronize immune cell functions through a regulated network of cytokines and chemokines. Since immune cell infiltration is prominent, we investigated the production of a responding chemoattractant, RANTES (regulated upon activation, normal T-cell expressed and secreted), in response to JEV infection of glial cells. Infection with JEV was found to elicit the production of RANTES from primary neurons/glia, mixed glia, microglia, and astrocytes but not from neuron cultures. The production of RANTES did not seem to be directly responsible for JEV-induced neuronal death but instead contributed to the recruitment of immune cells. RANTES expression required viral replication and the activation of extracellular signal-regulated kinase (ERK) as well as transcription factors, including nuclear factor kappa B (NF-kappaB) and nuclear factor IL-6 (NF-IL-6). The induction of RANTES expression by JEV infection in glial cells needed the coordinate activation of NF-kappaB and NF-IL-6. Using enzymatic inhibitors, we demonstrated a strong correlation between the ERK signaling pathway and RANTES expression. However, JEV replication was not dependent on the activation of ERK, NF-kappaB, and NF-IL-6. Altogether, these results demonstrated that infection of glial cells by JEV provided the early ERK-, NF-kappaB-, and NF-IL-6-mediated signals that directly activated RANTES expression, which might be involved in the initiation and amplification of inflammatory responses in the CNS.

Animals↗