Mechanisms of Action of Vanadium

Nechay, Bohdan R.

doi:10.1146/annurev.pharmtox.24.1.501

Cited by 217 publications

(71 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Humans consume appreciable amounts of V 5+ in food and water (Evangelou 2002). The estimated daily intake of V 5+ is 10 to 60 µg (Nechay 1984). In addition, the highest level of V 5+ supplements in multivitamin products reaches 25 µg/tablet or capsule.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and posttranscriptional regulation of CYP1A1 by vanadium in human hepatoma HepG2 cells

et al. 2010

View full text Add to dashboard Cite

We recently demonstrated that V(5+) downregulates 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 mRNA, protein, and catalytic activity levels in Hepa 1c1c7 cells through transcriptional mechanism. Therefore, it is important to investigate whether similar changes occur in humans. For this purpose, we examined the effect of V(5+) (as ammonium metavanadate, NH(4)VO(3)) on the expression of aryl hydrocarbon receptor (AhR)-regulated gene; cytochrome P450 1A1 (CYP1A1) at each step of the AhR signal transduction pathway in human hepatoma HepG2 cells. Our results show a significant reduction in TCDD-mediated induction of CYP1A1 mRNA, protein, and activity levels after V(5+) treatment in a dose-dependent manner. Investigating the effect of co-exposure to V(5+) and TCDD at transcriptional levels revealed that V(5+) significantly inhibited TCDD-mediated induction of AhR-dependent luciferase reporter gene expression. Looking at the posttranscriptional level, V(5+) did not affect CYP1A1 mRNA stability, thus eliminating the possible role of V(5+) in modifying CYP1A1 gene expression through this mechanism. On the other hand, at the posttranslational level, V(5+) was able to significantly decrease CYP1A1 protein half-life contributing to the inconsistency between catalytic activity and transcriptional level. Importantly, we showed that V(5+) did not significantly alter the heme oxygenase-1 mRNA level, thus eliminating any possibility that V(5+) might have decreased CYP1A1 activity through affecting its heme content. This study demonstrates for the first time that V(5+) downregulates the expression of CYP1A1 at the transcriptional, posttranscriptional and posttranslational mechanisms in the human hepatoma HepG2 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional and posttranscriptional regulation of CYP1A1 by vanadium in human hepatoma HepG2 cells

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Oxovanadium compounds can inhibit ion channel ATPases [23]. To assess if this underlies BMOV cytotoxicity, cells were treated with the Na + /K + channel blocker ouabain and Ca ++ channel blocker Table 1 Neuroblastoma cell lines used.…”

Section: Bmov Induces Cytotoxicity In Neuroblastoma Cellsmentioning

confidence: 99%

“…They can also suppress tumour growth and have chemopreventive properties [14,[19][20][21][22]. Inside cells, oxovanadium complexes exist largely in an equilibrium between vanadyl V(IV) and vanadate V(V) states, with V(V) being associated with PTP inhibition [23]. This V(IV)/V(V) equilibrium can also catalyse ROS generation through Fenton-like reactions and interactions with NADPH [14,19,24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Clark¹,

Park²,

Florio³

et al. 2015

Cancer Letters

View full text Add to dashboard Cite

In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic. This is not explained by oxidative stress or inhibition of ion channels. Genotoxicity is unlikely given that a p53 response is absent and p53-mutant lines are also sensitive. Cytotoxicity is inhibited by N-acetyl cysteine and glutathione ester, indicating that BMOV action is sensitive to cytoplasmic redox and thiol status. Significantly, combining BMOV with glutathione synthesis inhibition greatly enhances BMOV-induced cell death. This combination treatment triggers high AKT pathway activation, highlighting the potential functional importance of PTP inhibition by BMOV. AKT activation itself, however, is not required for cytotoxicity. Oxovanadium compounds may thus represent novel leads as p53-independent therapeutics for neuroblastoma.

show abstract

“…Several researches documented that vanadate inhibits Na + ,K + -ATPase of endoplasmic reticulum of the heart and smooth muscle cells of different tissues. Vanadate seems to block this enzyme by binding to its extra-and intra-cellular sites, respectively [34]. It has been found that acute leptin administration decreased Na + ,K + -ATPase activity in renal medulla of alloxan diabetic rats [40].…”

Section: Discussionmentioning

confidence: 99%

Effect of vanadium on renal Na+,K+-ATPase activity in diabetic rats: a possible role of leptin

2010

View full text Add to dashboard Cite

Several researches attempt to protect diabetic patients from the development of nephropathy. Involvement of leptin and renal Na+,K+-ATPase enzyme in diabetic nephropathy (DN) development is a recent field for researches. Vanadium, as a trace element with insulin mimetic effect, may act synergistically with insulin to protect against the development of DN. Sixty male Sprague Dawley rats were divided into six groups: control group (C), vanadium control group (CV), streptozotocin-induced diabetic group (D), insulin-treated diabetic group (DI), vanadium-treated diabetic group (DV), and combined insulin and vanadium-treated diabetic group. Six weeks later, systolic blood pressure (SBP) was measured and retro-orbital blood samples were collected to estimate glycosylated hemoglobin (HbA(₁c)), serum sodium (Na+) and creatinine, blood urea nitrogen (BUN) and plasma leptin levels. Preparation of microsomal fraction of renal tissue homogenate for estimation of Na+,K+-ATPase activity was done. The D group showed a significant increase in SBP, HbA(₁c), serum Na+, creatinine, and BUN levels and Na+,K+-ATPase activity in microsomal fraction of renal tissue homogenate while plasma leptin level decreased significantly compared with C and CV groups. Both DI and DV groups showed a significant improvement in all the above measured parameters compared with D group while there were no significant changes between the DI and DV groups. Concomitant treatment with insulin and vanadium resulted in a significant improvement in all the measured parameters compared to each alone. Vanadium in combination with insulin ameliorates DN markers and reduces renal Na+,K+-ATPase overactivity in diabetic rats. An effect that may be partially mediated through correction of hypoleptinemia observed in these animals.

show abstract

Mechanisms of Action of Vanadium

Cited by 217 publications

References 0 publications

Transcriptional and posttranscriptional regulation of CYP1A1 by vanadium in human hepatoma HepG2 cells

Transcriptional and posttranscriptional regulation of CYP1A1 by vanadium in human hepatoma HepG2 cells

Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine

Effect of vanadium on renal Na+,K+-ATPase activity in diabetic rats: a possible role of leptin

Contact Info

Product

Resources

About