Bisphenol blocks cell function


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From University of Boon, BPA blocks calcium channels in cell membranes. Dangerous.

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Bisphenol blocks cell function

  1. 1. Bisphenol A: BPA Additive Blocks Cell Function University of Bonn, Germany. experimentalement Dec. 6, 2012 — Bisphenol A, a substance found in many synthetic products, is considered to be harmful, particularly, for fetuses and babies. Researchers from the University of Bonn have now shown in experiments on cells from human and mouse tissue that this environmental chemical blocks calcium channels in cell membranes. Similar effects are elicited by drugs used to treat high blood pressure and cardiac arrhythmia. The results are now presented in the journal Molecular Pharmacology. The industrial chemical bisphenol A (BPA) is worldwide extensively utilized for manufacturing polycarbonates and synthetic resins. "This substance has been shown to affect the hormonal system and may have negative effects on the function of enzymes and carrier proteins," reports Prof. Dr. Dieter Swandulla from the Institute of Physiology II at the University of Bonn. BPA is associated with heart disease, diabetes, obesity, cancer, and neurological dysfunction. "It seems that fetuses and newborns are particularly sensitive to BPA," adds the physiologist. Due to its unpredictable effects, the EU Commission banned the use of BPA in baby bottles in 2011 as a precaution. Bisphenol A blocks multiple essential calcium channels The team of researchers around Prof. Swandulla now reports that BPA reversibly blocks calcium channels essential for cell function in mouse and human cells. Calcium ions flowing through these pore-like so-called channel proteins into living cells, control e.g. the contraction of heart muscle cells, the activity of enzymes, and the communication of nerve cells with each other. "Drugs such as those used to treat high blood pressure and cardiac arrhythmia on the one hand, and neurotoxins, such as heavy metals, on the other hand act on exactly the same calcium channels," explains the physiologist from the University of Bonn. "This indicates that BPA can indeed have adverse effects on human health." Since BPA binds to the calcium channels reversibly, there is at least the possibility of the chemical being eliminated from the body. Bisphenol A and its derivatives are ubiquitous Nowadays BPA and its related substances can be detected almost everywhere in the environment. Effective doses are found in CD's, paper money, thermal paper, food cans, dental fillings and flame retardants, even in the breathing air and in house dust. Humans are meanwhile chronically exposed to these compounds. "This is why it would be desirable to completely stop the production of BPA," says Prof. Swandulla. "Due to the high-volume production and its widespread occurrence, it would, however, take a very long time to remove this chemical from the environment and the human organism." Consequently, alternatives to BPA should be utilized which are harmless to humans and other organisms.
  2. 2. Bisphenol A Inhibits Voltage-Activated Ca2+ Channels in Vitro: Mechanisms and Structural Requirements. University of Bonn, Germany. experimentalement 1. André Deutschmann, 2. Michael Hans, 3. Rainer Meyer, 4. Hanns Häberlein, and 5. Dieter Swandulla + Author Affiliations 1. Institute of Physiology II (A.D., M.H., R.M., D.S.), Institute for Biochemistry and Molecular Biology (H.H.), University of Bonn, Bonn, Germany 1. Address correspondence to: Dr. D. Swandulla, Institute of Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, Germany. E-mail: Abstract Bisphenol A (BPA), a high volume production chemical compound attracts growing attention as a health-relevant xenobiotic in humans. It can directly bind to hormone receptors, enzymes, and ion channels to become biologically active. In this study we show that BPA acts as a potent blocker of voltage-activated Ca2+ channels. We determined the mechanisms of block and the structural elements of BPA essential for its action. Macroscopic Ba2+ / Ca2+ currents through native L-, N-, P/Q-, T-type Ca2+ channels in rat endocrine GH3 cells, mouse dorsal root ganglion neurons or cardiac myocytes, and recombinant human R-type Ca2+ channels expressed in human embryonic kidney (HEK) 293 cells were rapidly and reversibly inhibited by BPA with similar potency (EC50 values: 26–35 μM). Pharmacological and biophysical analysis of R-type Ca2+ channels revealed that BPA interacts with the extracellular part of the channel protein. Its action does not require intracellular signaling pathways, is neither voltage- nor use-dependent, and does not affect channel gating. This indicates that BPA interacts with the channel in its resting state by directly binding to an external site outside the pore-forming region. Structure-effect analyses of various phenolic and bisphenolic compounds revealed that 1) a double-alkylated (R-C(CH3)2-R, R- C(CH3)(CH2CH3)-R), or double-trifluoromethylated sp3 -hybridized carbon atom between the two aromatic rings and 2) the two aromatic moieties in angulated orientation are optimal for BPA’s effectiveness. Since BPA highly pollutes the environment and is incorporated into the human organism, our data may provide a basis for future studies relevant for human health and development. Footnotes • • Received July 26, 2012. • Accepted November 29, 2012. • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics