Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During recombinant Chinese hamster ovary (rCHO) cell culture, various events, such as feeding with concentrated nutrient solutions or the addition of base to maintain an optimal pH, increase the osmolality of the medium. To determine the effect of hyperosmotic stress on two types of programmed cell death (PCD), apoptosis and autophagy, of rCHO cells, two rCHO cell lines, producing antibody and erythropoietin, were subjected to hyperosmotic stress resulting from NaCl addition (310-610 mOsm/kg). For both rCHO cell lines, hyperosmolality up to 610 mOsm/kg increased cleaved forms of PARP, caspase-3, caspase-7, and fragmentation of chromosomal DNA, confirming the previous observation that apoptosis was induced by hyperosmotic stress. Concurrently, hyperosmolality increased the level of accumulation of LC3-II, a widely used autophagic marker, which was determined by Western blot analysis and confocal microscopy. When glucose and glutamine concentrations were measured during the cultures, glucose and glutamine concentrations in the culture medium at various osmolalities (310-610 mOsm/kg) showed no significant differences. This result suggests that induction of PCD by hyperosmotic stress occurred independently of nutrient depletion. Taken together, autophagy as well as apoptosis was observed in rCHO cells subjected to hyperosmolality.
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PMID:Hyperosmotic stress induces autophagy and apoptosis in recombinant Chinese hamster ovary cell culture. 2001 38

Hyperosmolality in recombinant Chinese hamster ovary (rCHO) cell cultures induces autophagy and apoptosis. To investigate the effect of Bcl-x(L) overexpression on autophagy and apoptosis in hyperosmotic rCHO cell cultures, an erythropoietin (EPO)-producing rCHO cell line with regulated Bcl-x(L) overexpression was subjected to hyperosmolality resulting from NaCl addition in a batch culture and nutrient supplementation in a fed-batch culture. In the batch culture, Bcl-x(L) overexpression suppressed apoptosis, as evidenced by a decreased amount of cleaved caspase-7 and PARP. Concurrently, Bcl-x(L) overexpression also delayed autophagy, as indicated by reduced LC3 conversion, from LC3-I to LC3-II. As a result, the cell viability and EPO production were improved by Bcl-x(L) overexpression. In the fed-batch culture, the simultaneous application of Bcl-x(L) overexpression and nutrient feeding increased the culture longevity and maximum EPO concentration. Taken together, Bcl-x(L) overexpression delayed autophagy and apoptosis in hyperosmotic rCHO cell cultures, resulting in increased EPO production.
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PMID:Bcl-x(L) overexpression delays the onset of autophagy and apoptosis in hyperosmotic recombinant Chinese hamster ovary cell cultures. 2187 25

Hepatocellular carcinoma (HCC) is one of the most difficult cancer disease for diagnosis and treatment, with a low survival rate and high recurrence rate and mortality. Nuclear factor of activated T-cells 5 (NFAT5) is mediated by osmolality and proved to be a carcinogenic gene in some tumor. However in our study we considered NFAT5 as tumor suppressor of HCC. RT-qPCR was performed for NFAT5 expression in tumor tissues. NaCl was applied to make hyperosmotic treatment. We knockdowned and overexpressed NFAT5 to investigate its role in HCC. FCM was used for apoptosis assay. Transwell and scratch assay is proceeded for invasion.NFAT5 is downregulated in HCC tissue and cell lines, besides, upregulated by hyperosmolality. NFAT5 promotes apoptosis by regulating PARP-1,BAX/BCL2 while inhibits invasion through EMT-related protein claudin-1 and fibronectin. Hyperosmolality is also a protective factor for HCC. We considered hyperosmolality exhibited his protective effect by inducing NFAT5.In a word, NFAT5 inhibits invasion and promotes apoptosis in HCC, associated with osmolality.
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PMID:NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality. 2848 55