Treatment with cystamine reduces apoptosis in liver from NZB/W F1 mice. 2008

Bor-Show Tzang, and Szu-Yi Chiang, and Wen-Xian Lai, and Chun-Chou Tsai, and Jen-Huang Wu, and Tsai-Ching Hsu
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, ROC. bstzang@csmu.edu.tw

Increased population with hepatic diseases and apoptosis were found in patients with SLE and implicated in the pathogenesis of SLE. Since cystamine has been demonstrated to be beneficial to NZB/W F1 mice in our previous report, this study intends to investigate the effects of cystamine in liver from NZB/W F1 mice. Decreased apoptosis was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS by TUNEL and caspase-3 activity assay. Fas-dependent apoptotic proteins including Fas, cleaved caspase-8 and tBid were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Additionally, the mitochondria-dependent apoptotic proteins including cytochrome c and Apaf-1 were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Moreover, increased BCL-2 protein was observed in liver from both mice. Notably, increased NF-kappaB protein was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS. These experimental results suggest the effect of cystamine in reducing apoptosis in liver from NZB/W F1 mice through Fas-dependent and mitochondrial-dependent pathways. The phosphorylation of NF-kappaB (p65) could be a possible mechanism involving anti-apoptotic effects of cystamine in liver from NZB/W F1 mice.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008180 Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Libman-Sacks Disease,Lupus Erythematosus Disseminatus,Systemic Lupus Erythematosus,Disease, Libman-Sacks,Libman Sacks Disease
D008814 Mice, Inbred NZB An inbred strain of mouse that is widely used as a model for AUTOIMMUNE DISEASES such as SYSTEMIC LUPUS ERYTHEMATOSUS. Mice, NZB,Mouse, Inbred NZB,Mouse, NZB,Inbred NZB Mice,Inbred NZB Mouse,NZB Mice,NZB Mice, Inbred,NZB Mouse,NZB Mouse, Inbred
D003538 Cystamine A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. Cystineamine,Decarboxycystine,Diaminodiethyldisulfide,2,2'-Dithiobisethanamine,Cystamine Calcium Salt,Cystamine Diacetate,Cystamine Dihydrobromide,Cystamine Dihydrochloride,Cystamine Hydrobromide,Cystamine Hydrochloride,Cystamine Sulfate,Cystamine Sulfate (1:1),Cysteinamine Disulfide,Cystinamin,2,2' Dithiobisethanamine,Calcium Salt, Cystamine,Diacetate, Cystamine,Dihydrobromide, Cystamine,Dihydrochloride, Cystamine,Disulfide, Cysteinamine,Hydrobromide, Cystamine,Hydrochloride, Cystamine,Sulfate, Cystamine
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females
D000097782 NF-kappaB-Inducing Kinase A protein serine-threonine kinase that catalyzes the activation of canonical and non-canonical NF-kappaB pathways. MAP3K14 Kinase,Mitogen-Activated Protein Kinase Kinase Kinase 14,NF-kappa B Kinase,NF-kappa-B-Inducing Kinase (NIK),NFkB Kinase,NIK Protein,Nuclear Factor kappa B Kinase,B Kinase, NF-kappa,Kinase, MAP3K14,Kinase, NF-kappa B,Kinase, NF-kappaB-Inducing,Kinase, NFkB,Mitogen Activated Protein Kinase Kinase Kinase 14,NF kappa B Kinase,NF kappaB Inducing Kinase,Protein, NIK
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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