Unifying Electrostatic Mechanism for Phosphates and Sulfates in Cell Signaling

Kovacic, Peter; Draskovich, Christine D.; Pozos, Robert S.

doi:10.1080/10799890701699702

Cited by 22 publications

(7 citation statements)

References 28 publications

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“…Cell signaling processes involve receptor ligand interactions which are based on electrostatic potentials associated with the ions and dipoles in the receptor ligand complex[66]. These types of interactions take place with all types of ions including the many cations and phosphates in biological systems and shift the energetics associated with electron transfer processes[101]. Redox properties of V complexes can be tuned from favoring one-electron transfer reactions to two-electron transfer reactions, potentially decreasing the toxicity of these complexes[66].…”

Section: 0 Interpretations Of the Observed Effects Of The Vdipic Comentioning

confidence: 99%

Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes

Willsky

Har

Godzala

et al. 2011

Coordination Chemistry Reviews

199

114

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The effects of oral treatment of rats with streptozotocin-induced diabetes with a range of vanadium dipicolinate complexes (Vdipic) and derivatives are reviewed. Structure-reactivity relationships are explored aiming to correlate properties such as stability, to their insulin-enhancing effects. Three types of modifications are investigated; first, substitutions on the aromatic ring, second, coordination of a hydroxylamido group to the vanadium, and third, changes in the oxidation state of the vanadium ion. These studies allowed us to address the importance of coordination chemistry, and redox chemistry, as modes of action. Dipicolinate was originally chosen as a ligand because the dipicolinatooxovanadium(V) complex (V5dipic), is a potent inhibitor of phosphatases. The effect of vanadium oxidation state (3, 4 or 5), on the insulin-enhancing properties was studied in both the Vdipic and VdipicCl series. Effects on blood glucose, body weight, serum lipids, alkaline phosphatase and aspartate transaminase were selectively monitored. Statistically distinct differences in activity were found, however, the trends observed were not the same in the Vdipic and VdipicCl series. Interperitoneal administration of the Vdipic series was used to compare the effect of administration mode. Correlations were observed for blood vanadium and plasma glucose levels after V5dipic treatment, but not after treatment with corresponding V4dipic and V3dipic complexes. Modifications of the aromatic ring structure with chloride, amine or hydroxyl groups had limited effects. Global gene expression was measured using Affymetrix oligonucleotide chips. All diabetic animals treated with hydroxyl substituted V5dipic (V5dipicOH) and some diabetic rats treated with vanadyl sulfate had normalized hyperlipidemia yet uncontrolled hyperglycemia and showed abnormal gene expression patterns. In contrast to the normal gene expression profiles previously reported for some diabetic rats treated with vanadyl sulfate, where both hyperlipidemia and hyperglycemia were normalized. Modification of the metal, changing the coordination chemistry to form a hydroxylamine ternary complex, had the most influence on the anti-diabetic action. Vanadium absorption into serum was determined by atomic absorption spectroscopy for selected vanadium complexes. Only diabetic rats treated with the ternary V5dipicOH hydroxylamine complex showed statistically significant increases in accumulation of vanadium into serum compared to diabetic rats treated with vanadyl sulfate. The chemistry and physical properties of the Vdipic complexes correlated with their anti-diabetic properties. Here, we propose that compound stability and ability to interact with cellular redox reactions are key components for the insulin-enhancing activity of vanadium compounds. Specifically, we found that the most overall effective anti-diabetic Vdipic compounds were obtained when the compound administered had an increased coordination number in the vanadium complex.

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Section: 0 Interpretations Of the Observed Effects Of The Vdipic Comentioning

confidence: 99%

Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes

Willsky

Har

Godzala

et al. 2011

Coordination Chemistry Reviews

199

114

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“…Discussion is present in recent reviews on receptor-ligand activity,108 phosphates and sulfates109 and metal cations 110…”

Section: Cell Signalingmentioning

confidence: 99%

Multifaceted Approach to Resveratrol Bioactivity: Focus on Antioxidant Action, Cell Signaling and Safety

Kovacic

Somanathan

2010

Oxidative Medicine and Cellular Longevity

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Resveratrol (RVT) is a naturally occurring trihydroxy stilbene that displays a wide spectrum of physiological activity. Its ability to behave therapeutically as a component of red wine has attracted wide attention. The phenol acts as a protective agent involving various body constituents. Most attention has been given to beneficial effects in insults involving cancer, aging, cardiovascular system, inflammation and the central nervous system. One of the principal modes of action appears to be as antioxidant. Other mechanistic pathways entail cell signaling, apoptosis and gene expression. There is an intriguing dichotomy in relation to pro-oxidant property. Also discussed are metabolism, receptor binding, rationale for safety and suggestions for future work. This is the first comprehensive review of RVT based on a broad, unifying mechanism.

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“…Significant impact on conformational structures was made by forces as weak as 0.5 pN. Therefore, it is reasonable to conclude that electrostatic energetics can play a role in biological processes, as suggested in our various reviews (2,3).…”

Section: Quantitative Aspectsmentioning

confidence: 86%

“…Prior reviews advanced the proposal of function as a conduit for electrons and radicals (1)(2)(3). A 2006 report on photosynthesis mechanism furnishes strong support for electrostatic action that energetically facilitates electron migration (4).…”

Section: Role Of Electrostatic Forcesmentioning

confidence: 93%

Unifying Electrostatic Mechanism for Metal Cations in Receptors and Cell Signaling

Kovacic

2008

Journal of Receptors and Signal Transduction

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Previously, an electrostatic mechanism was proposed for receptor-ligand action and for cell signaling by phosphate and sulfate. The hypothesis is further elaborated by application to metal ions, mainly calcium, magnesium, zinc, iron, and copper, in receptors and cell signaling. Evidence is provided for involvement of electrostatics in various reaction modes in biosystems. Calcium plays an important role electrochemically in neurotransmission. In some cases, electron transfer and redox processes are also involved. Electrostatics are known to participate in plant biochemistry. Mechanistically, the electrostatic field may act as a conduit for electrons and radicals and in involvement with energetics.

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Unifying Electrostatic Mechanism for Phosphates and Sulfates in Cell Signaling

Cited by 22 publications

References 28 publications

Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes

Anti-diabetic effects of a series of vanadium dipicolinate complexes in rats with streptozotocin-induced diabetes

Multifaceted Approach to Resveratrol Bioactivity: Focus on Antioxidant Action, Cell Signaling and Safety

Unifying Electrostatic Mechanism for Metal Cations in Receptors and Cell Signaling

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