Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenerative changes within keratinocytes. Despite the well-documented association between zinc deficiency and skin pathology, it is not clear which cellular processes are most sensitive to zinc deficiency and could account for the typical pathological features. We used the cultured HaCaT keratinocyte line to obtain insight into the cellular effects of zinc deficiency, as these cells show many characteristics of normal skin keratinocytes. Zinc deficiency was induced by growing cells in the presence of the zinc chelator, TPEN, or by growth in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a 44% reduction of intracellular zinc levels and a 75% reduction in the activity of the zinc-dependent enzyme, 5'-nucleotidase, relative to the control cells. Over a period of 7 days of exposure to zinc-deficient conditions, no changes in cell viability and growth, or in the cytoskeletal and cell adhesion systems, were found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by the presence of DNA fragmentation and expression of active caspase-3 in cells. These results demonstrate that apoptosis is the earliest detectable cellular change induced by zinc deficiency in HaCaT keratinocytes. Our observations account for many of the features of zinc deficiency, including the presence of degenerate nuclei, chromatin aggregates and abnormal organization of keratin, that may represent the later stages of apoptosis. In summary, a major causal role for apoptosis in the pathology of zinc deficiency in the skin is proposed. This role is consistent with the previously unexplained diverse range of degenerative cellular changes seen at the ultrastructural level in zinc-deficient keratinocytes.
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PMID:Apoptosis may underlie the pathology of zinc-deficient skin. 1640 50

Chikungunya infection is characterized by fever, rash and arthritis. The disease pathogenesis is still poorly understood. Hence, unveiling the molecular mechanisms that govern the survival and death of neuronal cells infected by Chikungunya virus (CHIKV) was the particular interest of this study. Human neuroblastoma SH-SY5Y cells infected with CHIKV showed characteristic features of apoptosis with activation of caspase-3, cleavage of PARP and translocation of Cyt-c. Cells also showed a loss in the intracellular level of GSH and an increase in the lipid peroxidation of the infected cells with the increasing time of infection, which indicated the involvement of oxidative stress in Chikungunya infection. There was observed a gradual decrease in the fold change of antioxidant enzymes and an increase in the fold change of pro-inflammatory cytokines. This study suggested the implication of virus induced apoptosis in disease pathogenesis which may give a fresh insight for CHIKV induced neuronal cell damage and antiviral therapeutics.
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PMID:Characterization of Chikungunya virus infection in human neuroblastoma SH-SY5Y cells: role of apoptosis in neuronal cell death. 2221 4