Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that manganese superoxide dismutase (MnSOD), an antioxidant enzyme, regulates the proliferative potential of confluent human fibroblasts. Normal human skin (AG01522) and lung (WI38, CCL-75) fibroblasts kept in confluence (>95% G(0)/G(1)) showed a significant decrease in their capacity to re-enter the proliferation cycle after 40-60 days. The inhibition of re-entry was accompanied with the age-dependent increase of p16 protein levels in the confluent culture. Adenoviral mediated overexpression of MnSOD during confluent growth suppressed p16, enhanced p21 protein accumulation, and protected fibroblasts against the loss of proliferation potential. Increases in p21 protein levels in MnSOD overexpressing confluent fibroblasts were independent of p53 protein levels. p53 protein levels did not change in control, replication-defective adenovirus containing an insertless vector (AdBgl II), or AdMnSOD-infected confluent cells cultured for 20 and 60 days. In addition, MnSOD-induced protection of the proliferation capacity of confluent fibroblasts was independent of their telomerase activity. However, telomerase-transformed fibroblasts showed increased MnSOD expression in confluent growth, maintaining their capacity to re-enter the proliferation cycle. Although inactivation of the retinoblastoma protein in cells subcultured from the 60-day confluent control, AdBgl II-, and AdMnSOD-infected fibroblasts was identical, only MnSOD-overexpressing cells showed a higher percentage of S-phase. These results support the hypothesis that a redox-sensitive checkpoint regulated the progression of fibroblasts from G(0)/G(1) to S-phase.
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PMID:Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts. 1574 56

To identify potential biomarkers for the monitoring and risk assessment of benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53 modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene exposure induced a decrease in the cell viability, but increased the antioxidant enzyme activity as well as the DNA and lipid damage. The p53 protein activation appeared to have been a downstream response to the benzo[a]pyrene-induced DNA damage, suggesting p53 plays important roles in the defense against benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA damage, the activation of p53 acts as a transcriptional regulator of several target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after the treatment of cells with benzo[a]pyrene, as well as following the induction of p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also be transcriptionally induced. The overall results suggest that benzo[a]pyrene leads to serious DNA damage, which leads to the transcription of the p53 gene; that the subsequent p53 protein accumulation up-regulates the cellular p21 protein. Oxidative DNA damage and p53 accumulation seem to be related to benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental monitoring and risk assessment needs to be validated in the context of their specificity and sensitivity.
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PMID:Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2 cells for the identification of potential biomarkers for PAH monitoring and risk assessment. 1702 27