Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylseleninic acid (MSA) has been shown to have potent anticancer activity and is an excellent compound for studying the anticancer effects of selenium in vitro. To gain insights into the effects of MSA in prostate cancer, we characterized the global transcriptional response of LNCaP, an androgen-sensitive human prostate cancer cell line, to MSA by using high-density cDNA microarrays. We identified 951 genes whose expression shows striking dose- and time-dependent changes in response to 3-30 microM MSA over the time course of 48 h. Transcript levels of many cell cycle-regulated genes change in response to MSA, suggesting that MSA inhibits proliferation. Consistent with these gene expression changes, cell proliferation, monitored by carboxyfluoroscein succinimidyl ester staining, was decreased after MSA treatment, and an accumulation of cells at G0/G1 phase was detected by flow cytometry. Surprisingly, MSA also modulated expression of many androgen-regulated genes, suppressed androgen receptor (AR) expression at both mRNA and protein level, and decreased levels of prostate specific antigen secreted into the medium. Low concentrations of MSA also induced significant increases in transcript levels of phase 2 detoxification enzymes and induced NADPH dehydrogenase, quinone 1 enzymatic activity, a surrogate marker of global phase 2 enzyme activity. Our results suggest that MSA may protect against prostate cancer by inhibiting cell proliferation, by modulating the expression of AR and AR-regulated genes and by inducing carcinogen defenses.
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PMID:Diverse effects of methylseleninic acid on the transcriptional program of human prostate cancer cells. 1461 3

Tribulus terrestris L. (Zygophyllaceae) have been used as an aphrodisiac both in the Indian and Chinese traditional systems of medicine. Administration of Tribulus terrestris extract (TT) increased sexual behaviour and intracavernous pressure both in normal and castrated rats and these effects were probably due to the androgen increasing property of TT. The objective of the present study is to evaluate the effect of TT on nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and androgen receptor (AR) immunoreactivity in rat brain. Twenty-four adult male Sprague-Dawley rats were divided into two groups of twelve each. Group I was treated with distilled water and Group II was treated with TT at the dose of 5mg/kg body weight orally, once daily for 8 weeks. Following treatment transcardiac perfusion was done with Ringer lactate, 4% paraformaldehyde and 30% sucrose. The brain tissue was removed and sections of the paraventricular (PVN) area of hypothalamus were taken for NADPH-d and AR immunostaining. There was an increase in both NADPH-d (67%) and AR immunoreactivity (58%) in TT treated group and these results were statistically significant compared to the control. Chronic treatment of TT in rats increases the NADPH-d positive neurons and AR immunoreactivity in the PVN region. Androgens are known to increase both AR and NADPH-d positive neurons either directly or by its conversion to oestrogen. The mechanism for the observed increase in AR and NADPH-d positive neurons in the present study is probably due to the androgen increasing property of TT. The findings from the present study add further support to the aphrodisiac claims of TT.
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PMID:Effect of Tribulus terrestris on nicotinamide adenine dinucleotide phosphate-diaphorase activity and androgen receptors in rat brain. 1558 60

The reduction in muscle mass and strength with age, sarcopenia, is a prevalent condition among the elderly, linked to skeletal muscle dysfunction and cell apoptosis. We demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Here, we analyzed the effect of testosterone on mitochondrial gene expression in C2C12 skeletal muscle cells. We found that testosterone increases mRNA expression of genes encoded by mitochondrial DNA, such as NADPH dehydrogenase subunit 1 (ND1), subunit 4 (ND4), cytochrome b (CytB), cytochrome c oxidase subunit 1 (Cox1) and subunit 2 (Cox2) in C2C12. Additionally, the hormone induced the expression of the nuclear respiratory factors 1 and 2 (Nrf-1 and Nrf-2), the mitochondrial transcription factors A (Tfam) and B2 (TFB2M), and the optic atrophy 1 (OPA1). The simultaneous treatment with testosterone and the androgen receptor antagonist, Flutamide, reduced these effects. H2O2-oxidative stress induced treatment, significantly decreased mitochondrial gene expression. Computational analysis revealed that mitochondrial DNA contains specific sequences, which the androgen receptor could recognize and bind, probably taking place a direct regulation of mitochondrial transcription by the receptor. These findings indicate that androgen plays an important role in the regulation of mitochondrial transcription and biogenesis in skeletal muscle.
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PMID:Testosterone induces up-regulation of mitochondrial gene expression in murine C2C12 skeletal muscle cells accompanied by an increase of nuclear respiratory factor-1 and its downstream effectors. 3167 90