Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic carcinoma is one of the most devastating neoplasms with regard to its resistance to conventional therapy. In a previous report, we found that endogenous tumor necrosis factor (enTNF) exerts an intracellular protective effect against exogenous TNF- and Adriamycin (ADM)-induced cytotoxicity by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD). We also know that glutathione S-transferase pi (GST-pi) and glutathione (GSH) also scavenge OFR. It remains unclear to what extent enTNF and MnSOD induced by enTNF regulate the sensitivity to ADM and exogenous TNF among different carcinoma cells. In this study, we examined the relationship between ADM and exogenous TNF sensitivity and en-TNF expression and MnSOD activity in four pancreatic carcinoma lines. We determined whether ADM and exogenous TNF sensitivity could be predicted by measuring enTNF expression and MnSOD activity in the carcinoma cells. The sensitivity to TNF and ADM varied with the cell lines, and TNF sensitivity correlated well with Adriamycin sensitivity. Moreover, enTNF expression and Mn-SOD activity correlated positively with resistance to ADM and exogenous TNF. When MIAPaCa-2 cells, which had the lowest enTNF expression and the highest sensitivity to exogenous TNF and ADM, were transfected with the nonsecretory-type human TNF gene (pTNF delta pro) to increase enTNF synthesis, their intracellular MnSOD activity and exogenous TNF and ADM resistance were increased. These findings suggest that MnSOD plays a critical role in scavenging OFR induced by ADM and exogenous TNF. enTNF is the most important factor that regulates the production of MnSOD. Therefore, it is plausible that inhibition of enTNF expression or MnSOD activity in pancreatic carcinoma would improve the efficacy of therapies for pancreatic carcinoma.
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PMID:Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells. 889

There are numerous studies describing the neuroprotective effects of Ginkgo biloba extract EGb 761 on patients with disturbances of vigilance, memory and cognitive functions associated with aging and senility. Describing the pattern of gene expression in EGb 761-treated human hNT neurons may elucidate the molecular pathways leading to the neuroprotection. We used cDNA macroarrays including genes implicated in the antioxidant and stress responses to define the transcriptional effects of EGb 761 (250 microg/ml, 24 hr) on human hNT neurons. Seven genes were identified whose expression was strongly modified by the EGb 761 treatment. Three groups are distinguished: genes encoding transcription factors (increase of NF-kappaB p65 subunit and zinc finger protein 91 mRNAs, and decrease of c-myc transcripts), genes involved in antioxidant defenses (increase of the CuZn SOD mRNAs, and decrease of glutathione reductase and glutathione S-transferase pi mRNAs) and genes involved in stress responses (up-regulation of HSP70 transcripts). Consistent with the modulation of mRNAs by EGb 761, the enzymatic activities of glutathione reductase and glutathione S-transferase were decreased. Surprisingly, CuZn SOD activity was decreased despite increased abundance of the mRNAs; furthermore MnSOD activity was unmodified, and thus the effect of EGb 761 was specific to CuZn SOD. These results support the idea that modulation of target genes and transcription factors may be involved in the neuroprotective action of EGb 761.
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PMID:The Ginkgo biloba extract EGb 761 increases viability of hnt human neurons in culture and affectsthe expression of genes implicated in the stress response. 1239 74