1.Pro-apoptotic function of hepatitis B virus X protein.
The Korean Journal of Hepatology 2010;16(2):112-122
Infection of hepatitis B virus (HBV) is a main cause of liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Among the HBV-encoded proteins, the HBV X protein (HBx) has been suspected to be strongly involved in HBV-associated liver pathogenesis. HBx, a virally encoded multifunctional regulator, has been shown to induce apoptosis, anti-apoptosis, proliferation, and transformation of cells depending on the cell lines, model systems used, assay protocols, and research groups. Among the several activities of HBx, the pro-apoptotic function of HBx will be discussed in this review. Given that the disruption of apoptosis pathway by HBx contributes to the liver pathogenesis, a better understanding of the molecular interference in the cellular pro-apoptotic networks by HBx will provide useful clues for the intervention in HBV-mediated liver diseases.
*Apoptosis
;
Hepatitis B/etiology
;
Liver Diseases/metabolism/virology
;
Trans-Activators/*metabolism
;
Tumor Necrosis Factors/metabolism
;
Tumor Suppressor Protein p53/metabolism
2.Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway.
Dong Jo KIM ; Jun Ho CHUNG ; Eun Kyeong RYU ; Jung Hyo RHIM ; Yoon Sic RYU ; So Hyun PARK ; Kyung Tae KIM ; Heun Soo KANG ; Hong Keun CHUNG ; Sang Chul PARK
Experimental & Molecular Medicine 2006;38(4):401-407
Although the apoptosis of chondrocytes plays an important role in endochondral ossification, its mechanism has not been elucidated. In this study, we show that guanosine induces chondrocyte apoptosis based on the results of acridine orange/ ethidium bromide staining, caspase-3 activation, and sub-G1 fraction analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter blocker, indicates that extracellular guanosine must enter the chondrocytes to induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel mechanism for endochondral ossification via metabolic regulation.
Tumor Necrosis Factors/metabolism
;
Signal Transduction/drug effects
;
Receptors, Tumor Necrosis Factor/*metabolism
;
Rats, Sprague-Dawley
;
Rats
;
Nucleoside Transport Proteins/metabolism
;
Membrane Glycoproteins/metabolism
;
Guanosine/*pharmacology/physiology
;
Fas Ligand Protein
;
Chondrocytes/*drug effects/metabolism
;
Apoptosis/*drug effects
;
Antigens, CD95
;
Animals
3.New components of the necroptotic pathway.
Zhenru ZHOU ; Victor HAN ; Jiahuai HAN
Protein & Cell 2012;3(11):811-817
Programmed necrosis, also known as necroptosis, has recently drawn great attention. As an important cellular regulation mechanism, knowledge of its signaling components is expanding. Necroptosisis demonstrated to be regulated by the RIP1 and RIP3 kinases, and its pathophysiological importance has been confirmed in a number of disease models. Here we review the new members of this necroptosis pathway, MLKL, PGAM5, Drp1 and DAI, and discuss some of their possible applications according to recent findings.
Animals
;
Carrier Proteins
;
metabolism
;
DNA-Binding Proteins
;
metabolism
;
GTP Phosphohydrolases
;
metabolism
;
Humans
;
Microtubule-Associated Proteins
;
metabolism
;
Mitochondrial Proteins
;
metabolism
;
Necrosis
;
Phosphoprotein Phosphatases
;
Protein Kinases
;
chemistry
;
metabolism
;
Receptor-Interacting Protein Serine-Threonine Kinases
;
metabolism
;
Signal Transduction
;
Tumor Necrosis Factors
;
metabolism
4.Effect of chlorine gas pulmonary emphysema on IL-8 and TNF in rats.
Shan WU ; Zhi-xie JUNG ; yan-lung SHEN ; Ming SHEN ; Yi ZHOU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2003;21(4):283-284
Animals
;
Chlorine
;
toxicity
;
Interleukin-8
;
metabolism
;
Lung
;
drug effects
;
metabolism
;
pathology
;
Male
;
Pulmonary Emphysema
;
chemically induced
;
metabolism
;
Rats
;
Rats, Wistar
;
Time Factors
;
Tumor Necrosis Factor-alpha
;
metabolism
5.Relationship between activation of microglia and Jaks phosphorylation induced by microwave irradiation.
Xue-sen YANG ; Yu-tong HAO ; Gen-lin HE ; Chun-hai CHEN ; Yuan WANG ; Guang-bin ZHANG ; Zheng-ping YU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(6):401-404
OBJECTIVETo explore the relationship between microglial proinflammatory and electromagnetic radiation and unveil the role of microglia in microwave radiation induced central nervous system injury.
METHODSN9 microglia cells cultured in vitro were exposed to microwave at 90 mW/cm2. Cell flow cytometry was used to observe the expression of CD11b at different time points after exposure; ELISA was used to detect the concentration of TNF-alpha in N9 cell culture supernatant; RT-PCR analysis confirmed iNOS mRNA expression in N9 microglia cells; and Nitrate Reductase Method was used to test NO amount in culture supernatant.
RESULTSThe CD11b positive microglial cells increased significantly at 3 h after microwave exposure (P < 0.05), continued to increase until 24 h and peaked at 6 h after exposure. The amount of TNF-alpha rose dramatically from 1 h to 24 h after exposure (P < 0.01) and peaked at 3 h [(762.1 +/- 61.5) pg/ml] after exposure (P < 0.01). The level of NO started to increase at 1 h [(4.48-0.59) micromol/L] and lasted for 24 h after exposure. The expression of iNOS mRNA increased significantly at 1 h (P < 0.05), and tripled the original expression at 6 h after exposure, hereafter, it decreased slightly, but all were higher than the control group within 24 h after exposure.
CONCLUSIONMicrowave radiation could induce the activation of microglia cells. The activated microglia cells could induce microglial proinflammatory by producing large amounts of TNF-alpha, NO, etc.
Animals ; Cell Line ; Cells, Cultured ; Mice ; Microglia ; metabolism ; radiation effects ; Microwaves ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Phosphorylation ; RNA, Messenger ; genetics ; Tumor Necrosis Factors ; metabolism
6.The effects of early escharectomy on resting energy expenditure in the severely burned patients.
Jian-chuan GAO ; Jia-ke CHAI ; Hong-ming YANG ; Zhi-yong SHENG ; Dai-feng HAO ; Zhen-rong GUO
Chinese Journal of Burns 2004;20(1):37-39
OBJECTIVETo investigate the effect of early escharectomy on resting energy expenditure (REE) in severely burned patients dynamically with the metabolic monitoring and diagnostic system.
METHODSFifty-six adult male patients with severe burns were divided into early escharectomy (group A, n = 39, escharectomy within 5 PBDs) and non-early escharectomy (group B, n = 17, escharectomy after 5 PBDs) groups. The wounds of full thickness and deep partial thickness burn in the two groups were all excised and covered with allogeneic skin and autologous micro-skin in the first operation. The changes in REE were observed dynamically at the bedside of the patients with the metabolic monitoring and diagnostic system. The plasma contents of IL-6, IL-8, TNF-alpha and LPS from 9 patients in group A and 7 in group B were also determined dynamically.
RESULTSAll patients survived. The REE in both groups was elevated markedly, but REE in group A was lower compared with group B before and after escharectomy within 14 days. (P < 0.05). The plasma level of IL-6, IL-8, TNF-alpha and LPS in group A were obviously lower than those in group B (P < 0.05).
CONCLUSIONThe hypermetabolic response of burn patients with severe burns could be lowered by early escharectomy, and it seemed to be related to the decrease of the release of proinflammatory mediators.
Adult ; Basal Metabolism ; Burns ; metabolism ; physiopathology ; surgery ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Lipopolysaccharides ; blood ; Male ; Postoperative Care ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; metabolism
7.Analyses of EGF and TNF contents in fetal wound healing process.
Guoping FENG ; Guangci SUN ; Zhengyu GUAN
Chinese Journal of Plastic Surgery 2002;18(6):341-342
OBJECTIVETo investigate the role of EGF and TNF in the fetal wound healing process.
METHODSOn a fetal wound healing model with the maternal rabbit on 22-23 days of pregnancy (term = 31-32 days), the contents of EGF and TNF were analyzed with a RIA kit, compared to the maternal rabbit group and the adult rabbit group.
RESULTSThe EGF and TNF contents in the fetal wound were both increasing 3 days after the operation and maintained in a high level until the 7th day of the wound healing process(P < 0.05). However, the EGF and TNF contents in the maternal and adult rabbit groups were only kept at a high level during the 3 days after the surgery.
CONCLUSIONThe results are indicated that the EGF and TNF may play an important role in fetal wound healing.
Animals ; Epidermal Growth Factor ; metabolism ; Female ; Fetus ; metabolism ; surgery ; Pregnancy ; Rabbits ; Radioimmunoassay ; methods ; Time Factors ; Tumor Necrosis Factor-alpha ; metabolism ; Wound Healing
8.MCP-1-induced protein-1, an immune regulator.
Jiwei XU ; Sheng FU ; Wei PENG ; Zihe RAO
Protein & Cell 2012;3(12):903-910
MCP-1-induced protein-1 (MCPIP1) is a newly identified protein that is crucial to immune regulation. Mice lacking MCPIP1 gene suffer from severe immune disorders, and most of them cannot survive longer than 12 weeks. Considerable progress has been made in revealing the mechanism underlying the immune regulatory function of MCPIP1. MCPIP1 can act as an RNase to promote the mRNA degradation of some inflammatory cytokines, such as IL-6 and IL-1. Pre-microRNAs are also confirmed to be the substrate of MCPIP1 RNase. The structure of MCPIP1 N-terminal conserved domain shows a PilT N-terminus-like RNase structure, further supporting the notion that MCPIP1 has RNase activity. MCPIP1 can also deubiquitinate TNF receptor-associated factor family proteins, which are known to mediate immune and inflammatory responses. In this review, we summarize recent progress on the immune regulatory role of MCPIP1 and discuss the mechanisms underlying its function.
Amino Acid Sequence
;
Animals
;
Humans
;
Immunity
;
Molecular Sequence Data
;
Ribonucleases
;
metabolism
;
Transcription Factors
;
chemistry
;
metabolism
;
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
;
metabolism
;
Ubiquitination
9.Effect of inflammatory cytokines on the expression of Krupple-like factor 4 in endothelium.
Journal of Experimental Hematology 2009;17(6):1551-1554
The aim of this study was to investigate the expression of Krupple-like factor 4 (KLF-4) in human umbilical vein endothelial cells (HUVEC) under stimulating of cytokines IL-1beta and TNF-alpha. The HUVEC were isolated, cultured and exposed to IL-1beta, TNF-alpha for 2 and 4 hours, the expression level of KLF-4 mRNA was detected by real-time PCR, the expression level of KLF-4 protein was measured by Western blot, the location of KLF-4 in HUVEC was determined by confocal laser microscopy. The results showed that the KLF-4 mRNA lowly expressed in normal HUVEC, but highly expressed in HUVEC after stimulation with IL-1beta and TNF-alpha; furthermore the expressions of KLF-4 mRNA and protein were enhanced along with prolonging of time. Confocal laser microscopy showed that the expression of KLF-4 was enhanced in nucleus and plasma of HUVEC after stimulating with IL-1beta. It is concluded that the expression of KLF-4 increases under IL-1beta and TNF-alpha stimulation which may participate in regulation of endothelial activity.
Cells, Cultured
;
Endothelium
;
metabolism
;
Humans
;
Interleukin-1beta
;
pharmacology
;
Kruppel-Like Transcription Factors
;
metabolism
;
RNA, Messenger
;
metabolism
;
Tumor Necrosis Factor-alpha
;
pharmacology
10.A analysis of ELISA on the time-related expression of IL-2 and TNF-alpha during the healing process of wound in rat skin.
Journal of Forensic Medicine 2003;19(1):10-12
OBJECTIVE:
In order to explore the relationship between the expression change of cytokines and the wound age during the healing process of rats skin wound.
METHODS:
A assay of ELISA were performed on intravital skin wounds(after incision 0.5-168 h) to detect the dynamics expression level of IL-2, TNF-alpha.
RESULTS:
The level of IL-2 and TNF-alpha increased at 0.5 h after wounding, then got to a peak at 3 h and 1 h after injure respectively. Rebound of TNF and IL-2 levels were shown at 48 h after wounding, and both cytokine levels were inclined to elevating between 72 h and 168 h after wounding.
CONCLUSION
The cytokine level changes suggest they have a time-related expression during wounds healing process.
Animals
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Interleukin-2/metabolism*
;
Male
;
Rats
;
Rats, Wistar
;
Skin/metabolism*
;
Time Factors
;
Tumor Necrosis Factor-alpha/metabolism*
;
Wound Healing/physiology*