The interactomes of these proteins were extracted from the STRING database of protein-protein interactions (https://string-db.org). Giotakos O, Nisianakis P, Tsouvelas G, Giakalou V-V. Lithium in the public water supply and suicide mortality in Greece. doi: 10.1093/nar/gkw937, 42. doi: 10.1083/jcb.200504035, 22. This explains why the effects of lithium are widespread and varied; lithium has a modulating effect on many gene networks. Sleire L, Frde-Tislevoll HE, Netland IA, Leiss L, Skeie BS, Enger P. . For a detailed discussion of empirical p-value determination see Ge et al. In addition to this, the way a lithium-ion battery produces power also generates heat as a by-product. December 15, 2020 Myth: Exposure to the electromagnetic fields of the battery in an electric vehicle could cause cancer. Yumiko M, Shimada K, Ishiguro K, Hattori N. Lithium and autophagy. It appears that the interactomes of five out of the 17 lithium-sensitive genes (ADCY2, ADCY5, ADCY7, BPNT1, and HIPK3) do not show significant mutual enrichment with the cancer pathways explored in this study. Dall'Era MA, Albertsen PC, Bangma C, Carroll PR, Carter HB, Cooperberg MR, et al. (1992) 34:299319. Bipolar Disorder Treatments and Ovarian Cancer: A Systematic Review. doi: 10.1038/ki.2014.2, 18. It is the presence of these lithium ions that yield superior battery performance, allowing the battery to store a large amount of energy in a relatively small area, which is why these batteries are so useful and common. Aims: To investigate the association between lithium and cancer risk in patients with bipolar disorder. doi: 10.1016/j.jpsychires.2012.12.002, 69. Int J Neuropsychopharmacol. The original article by Markham Heid was published on the blogging platform Medium. Both elements are needed to make lightweight rechargeable batteries for electric cars and . Risks for these cancers were 1.47, 1.72 and 2.6 times higher, respectively. Oncogene. Before Front. This size is large enough for statistically reliable enrichment analysis. With the addition of GSK3A (38), we have a list of 17 phosphate-transfer enzymes directly inhibited by lithium. Inhibition of glycogen synthase kinase-3 represses androgen receptor activity and prostate cancer cell growth. Table 1. 2013;8(4):e61457. For the remainder of the genes and the remainder of the cancers, the relationship between the lithium-sensitive interactome and the cancer phenotype is strong. Martinsson L, Westman J, Hllgren J, sby U, Backlund L. Lithium treatment and cancer incidence in bipolar disorder. Acta Neuropathol Commun. It is not clear from our reading of the two ovarian cancer papers why the results are significantly different from each other. and transmitted securely. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, Mclauchlan H, et al. Lithium-ion batteries are used in a wide range of hardware, from electric vehicles and electric scooters to mobile phones and laptops. Autophagy is a key cellular process in the inhibition of cancer (20). Wasserstein RL, Nicole A, Lazar NA. However, lithium-ion batteries are more useful and therefore much more popular as they combine fast charging, long charge holding and high power density, for more battery life in a smaller package. For a patient with a reliable diagnosis of bipolar disorder a common target for optimality would be blood concentration of 0.81 mM. (2014) 2014:241864. doi: 10.1155/2014/241864, 15. Growing evidence identifies effects of Li on cancer proliferation through inhibition of glycogen synthase kinase-3 (GSK-3), modulations of redox status, inflammatory changes, pro-/anti-apoptotic mechanisms, and mitochondrial function changes. This document is subject to copyright. (2016) 166:28898. Because mutations in G protein linked receptors have emerged as of interest in cancer research (28), it is significant that lithium appears to inhibit -adrenergic and muscarinic receptor coupling to G proteins by competing with magnesium, which facilitates such coupling (2933). Oncol. Towards a unified understanding of lithium action in basic biology and its significance for applied biology. Source: University of California - San Diego. Lithium has many widely varying biochemical and phenomenological effects, suggesting that a systems biology approach is required to understand its action. Contact, Courses doi: 10.1038/bjc.2016.10, 8. ^https://clinicaltrials.gov/ct2/show/NCT02198859, 1. Behav Brain Res. Serum lithium as a compliance marker for food and supplement intake. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation. Lithium enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells. Am J Physiol. Biophys J. Additional education and training, especially for tradespeople, can also help to increase knowledge and understanding regarding the dangers of lithium-ion batteries and help to minimize risks and eliminate danger as much as possible. On closer look, the Denmark study does not contradict the Swedish study. (2013) 13:412. doi: 10.1038/nrc3521, 29. doi: 10.1002/pros.21300, 11. Figure 1. The work was subsequently extended to an animal model (10). WG did the computations and prepared the figures and tables. Even the highest values of EMF exposure in the EVs, which would occur when starting the car and being located closest to the battery, do not yield any health concerns. Another important marker is provided by a study showing that over a 4-year period a lithium level of 0.250.4 mM of lithium (1/4 to 1/2 of the bipolar therapeutic dose) did not incur any renal damage (70). Batteries should not be exposed to high external temperatures, for example from being left in direct sunlight for long periods of time. Hopefully, with more research, we can expand our understanding of lithium and its potential use in cancer treatment. Each of the remaining 11 interactomes show strong mutual enrichment with most of the cancer-relevant pathways. Your email address is used only to let the recipient know who sent the email. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc. (2016) 114:5715. Of nine different adenylyl cyclases tested, two (ADCY5 and ADCY7) are strongly inhibited by lithium and one (ADCY2) is less strongly but significantly inhibited (37). Ge W, Jakobsson E. Systems biology understanding of the effects of lithium on cancer. For treatment, most of the research focuses on lithium as an adjunctive therapy in combination with other cancer therapies to increase cancer cell death and improve overall survival. Because lithium therapy is systemic rather than topical or local, it follows that lithium might inhibit metastasis. Extreme lithium deprivation results in failure to thrive, while too much lithium is toxic. A promising strategy is to combine lithium with other therapies. 2019;33(10):2429-2441. doi:10.1038/s41375-019-0454-4, Kotliarova S, Pastorino S, Kovell LC, et al. Lithium reacts intensely with water, forming lithium hydroxide and highly flammable . Biochem J. Novetsky AP, Thompson DM, Zighelboim I, Thaker PH, Powell MA, Mutch DG, et al. 1980;255(22):10896-10901. p. 3343. Symptoms of lithium . Find Sustainable Sources of Lithium 4. Sci Rep. (2016) 6:20739. doi: 10.1038/srep20739, 20. Names and synonyms for the known human lithium-sensitive enzymes and the genes that code for them, derived from entries in the UniProt database. This study confirms the safety and efficacy of the main . Glioblastomas are aggressive brain tumors with an average life expectancy of less than two years. The site is secure. doi: 10.1007/BF02787342, 5. "We want and need this energy storage technology to be safe because they are vital in the uptake of renewable energy and it's important that the public and industry do not perceive it to be dangerous. Schrauzer GN. This gives us a measure of the false discovery rate, since any overlap between the null sets and the KEGG pathways is purely accidental. Residential solar battery systems also utilize the technology, all the way up to grid-scale energy storage systems. If you drop your phone too hard (or too many times), there's a chance you'll damage the separator and cause the electrodes to touch. PLoS One. Federal government websites often end in .gov or .mil. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. The Swedish study also found that for the entire population lithium was not correlated with cancer incidence, but in addition found that bipolar individuals not treated with lithium had a higher incidence of cancer than the general population. (2014) 86:18490. Prostate. The batteries are found everywhere in laptop computers, cameras, cell phones, and electric cars. For all its complexity, there are only a few confirmed targets of lithium that show enzyme inhibition and biological consequences at achievable lithium concentrations: inositol monophosphatase and the related magnesium-dependent phosphomonoesterases and glycogen synthase kinase-3 (GSK-3) (Hallcher 1980, Phiel 2001). (2017) 2017:218248. doi: 10.1101/218248, 49. The BMS tracks data including temperature, cell voltage, cell current, and cell charge to help ensure that each part of the battery is working correctly and safely. Integrative Psychiatry Fellowship, Articles Post RM. (2012) 62:97683. Early work with glioblastoma has shown potential benefits. Pottegrd A, Ennis ZN, Hallas J, Jensen BL, Madsen K, Friis S. Long-term use of lithium and risk of colorectal adenocarcinoma: a nationwide case-control study. Klein, Peter [corrected to Klein, Peter S]]. In addition to the labeled specific cancer pathways we extended the analysis to signaling pathways in which dysfunction is implicated in cancer, as indicated in the literature (4956). Other external factor can cause a lithium-ion battery to fail, too. Zhukova et al. J Cell Biol. While MYC is considered an oncogene, it has both pro and anticarcinogenic activity. The hedgehog signalling pathway is involved in fetal development, cellular growth and cellular reproduction. Flow diagram of the steps to compute empirical p-values for the mutual enrichment between the interactomes of lithium-sensitive enzymes and cancer-relevant pathways. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. Cell. You also have the option to opt-out of these cookies. Int J Med Sci. Eur Urol. A drug cocktail, including lithium, was trialled in seven glioblastoma patients and demonstrated increased survival (Furuta 2017). Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. J Psychiatr Res. Sun A, Shanmugam I, Song J, Terranova PF, Thrasher JB, Li B. Lithium suppresses cell proliferation by interrupting E2F-DNA interaction and subsequently reducing S-phase gene expression in prostate cancer. Pickett EE, O'Dell BL. Br J Psychiatry. doi: 10.1007/s00232-017-9998-2, PubMed Abstract | CrossRef Full Text | Google Scholar, 3. This should, in theory, lead to a far greater Drive Electric Colorado presents an EVs in Colorado report. Awareness Isnt Enough: Suicide Rates and the Failure of Mainstream Mental Health Care. Curr Med Res Opin. doi: 10.1192/bjp.bp.108.055798, 66. These enzymes all have a magnesium binding site, and lithium, with an ionic radius similar to magnesium, appears to block magnesium binding, inhibiting the enzymes. Lithium, by decreasing GSK-3 activity, promotes glycogen production. Special lithium-ion gel extinguishers do exist but are not yet widely available for all lithium-ion battery applications. All Rights Reserved. Lithium and Not Acetoacetate Influences the Growth of Cells Treated with Lithium Acetoacetate. Mobile phones, laptops and smart wearables are all powered with lithium-ion batteries, as are newer e-mobility products such as e-bikes and e-scooters. 2018;13(12):e0208094. (1990) 25:10513. Forn J, Valdecasas FG. doi: 10.1007/s12011-013-9815-4, 68. Cell. The major issue with lithium-ion batteries overheating is a phenomenon known as thermal runaway. They found a 27% reduction in risk of cancer with lithium, noting that the higher the dose, the greater the reduction in cancer risk (Huang 2016). (2007) 26:3279. doi: 10.1038/sj.onc.1210421, 57. de Roos NM, de Vries JHM, Katan MB. (1991) 41:1715. December 13, 2018 White pills The European Medicine Agency has reported that there may be an association between long-term lithium use and reports of both renal tumors and thyroid cancer. 1997;273(3 Pt 1):E514-E520. For general inquiries, please use our contact form. Figure 2 shows mutual lithium interactome enrichment with specific cancer pathways, represented by heatmaps. A common underlying biophysical basis for competition between lithium and magnesium for modulating phosphate-transfer enzymes, is suggested by noting that the primary energy source for cells and the substrate for phosphorylating enzymes is not bare ATP, but rather magnesium-associated ATP (MgATP) (26). Mann L, Heldman E, Shaltiel G, Belmaker RH, Agam G. Lithium preferentially inhibits adenylyl cyclase V and VII isoforms. Am J Clin Nutr. This article has been reviewed according to ScienceX's Because of this policy, approximately 1.15 x 10 5 . The Results: Patients who used lithium had a statistically significant reduction in over all cancer rates in comparison to patients who used only anticonvulsants. Make Lithium Ion Batteries Long-Lasting 3. Zaidan M, Stucker F, Stengel B, Vasiliu V, Hummel A, Landais P, et al. Epub 2016 Oct 24. doi: 10.1093/nar/gks1094, 46. (2017) 116:1302. doi: 10.1038/bjc.2017.89, 24. J Biol Chem. Published 2013 Apr 23. doi:10.1371/journal.pone.0061457, Zhang Q, Zhang Q, Li H, Zhao X, Zhang H. LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells. Battery . Despite the presence of contradictory data, a substantial body of evidence mainly from molecular studies points to Li's anti-carcinogenic effects. The role of Lithium (Li) in cancer proliferation/inhibition is still a controversial issue in the literature. 2019 Nov 22;:. Kapusta ND, Mossaheb N, Etzersdorfer E, Hlavin G, Thau K, Willeit M, et al. Neither your address nor the recipient's address will be used for any other purpose. The difference with lithium-ion batteries available on the market today is that they typically contain a liquid electrolyte solution with lithium salts dissolved into a solvent, like ethylene carbonate, to create lithium ions. Drug repurposing in cancer. Unable to load your collection due to an error, Unable to load your delegates due to an error. March 21, 2019 By Casey Halter Tweet Advertisement An article that went viral suggests that Apple AirPods and other wireless headphones could be increasing people's risk for cancer. Maeng Y-S, Lee R, Lee B, Choi S-I, Kim FA. Unfortunately, lithium-ion battery fires are also not easily contained and are self-sustaining which is why they are considered more volatile than other battery types. Thinning of hair or hair loss. The thermal runaway phenomenon means lithium-ion battery fires are extremely hard to put out. Lithium and inhibition of GSK3 as a potential therapy for serous ovarian cancer. Duffy DJ, Krstic A, Schwarzl D, Higgins DG, Kolch W. GSK3 inhibitors regulate MYCN mRNA levels and reduce neuroblastoma cell viability through multiple mechanisms, including p53 and Wnt signaling. Received: 04 January 2019; Accepted: 01 April 2019; Published: 30 April 2019. But when they looked at what's been happening in the . Blml V, Regier MD, Hlavin G, Rockett IRH, Knig F, Vyssoki B, et al. Method: Therefore, lithium concentration in both extracellular and intracellular compartments, rather than being nearly constant as is the case with other ions, is roughly proportional to lithium ingestion (57). We would like to show you a description here but the site won't allow us. GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3. "But at the moment, most people do not have an adequate understanding about the risks associated with these batteries, or enough respect for them. (2005) 170:110111. Myth BUSTED: The magnetic fields in electric vehicles pose no danger because their electromagnetic field levels are below the recommended standards. Cookies are used on this website provide the most relevant viewing experience. (2016) 209:3939. doi: 10.1192/bjp.bp.110.091041, 70. Other rechargeable battery types do exist and are widely usedsuch as nickel-cadmium and even lead-acid which date back to the 19th century. Nucleic Acids Res. A detailed study of molecular mechanisms by which lithium inhibition of GSK3-beta inhibits proliferation of prostate tumor cells in culture was presented by Sun et al. This site uses cookies to assist with navigation, analyse your use of our services, collect data for ads personalisation and provide content from third parties. J Am Soc Nephrol. Biochem Pharmacol. We present evidence of a female patient with bipolar disorder I, who had been on Li for several years, either as monotherapy or in combination with Valproate (VPA). Analysis was performed on the interactomes of the above-mentioned lithium-sensitive proteins. A very useful tool for obtaining data about known pathways is the KEGG database (40). doi: 10.3892/ijo.2015.2911, 16. Disclaimer. Scientists have uncovered a root cause of the growth of needle-like structures -- known as dendrites and whiskers -- that plague lithium batteries, sometimes causing a short circuit, failure, or . GSK-3 inhibitors enhance TRAIL-mediated apoptosis in human gastric adenocarcinoma cells. We note that screening for lithium sensitivity has so far not included systematic examination of multiple variants of particular gene products, either mutational variants or alternative splices from the same gene. 2020;21(17):6410. doi: 10.1007/s00428-005-1264-9, 55. Clin Cancer Res. Evidence that this is the case for colon cancer comes from observation of inhibition of metastasis-inducing factors by lithium and by observation on reduced metastasis in model animals given lithium therapy (19). Protein Sci. Epub 2016 Mar 19. We used the R-package KEGGgraph (42, 43) to identify the proteins and genes associated with the cancer-relevant pathways. (2018) 173:32137. Han S, Meng L, Jiang Y, Cheng W, Tie Xia XJ, et al. Based on a clinical case with lithium intake and development of a renal tumor, we aimed to explore the relationship between Li use and tumor proliferation, with regard to the mechanism of action of Li. A literature search was performed using keywords bipolar disorder, medical comorbidity, cancer, renal tumor, lithium, mood stabilizers, valproate and mechanism of action. Nucleic Acids Res. When this need arises it typically comes after only a few years. WG wrote the first draft of the Methods and Results sections. Lithium batteries can cause landfill fires that can smolder for many years. (2016) 45:D35361. doi: 10.1158/1535-7163.MCT-13-0560-T, 12. What Does Maintenance Actually Mean for an EV Owner? All types of batteries can be hazardous and can pose a safety risk. Electric vehicles, such as Teslas, use lithium-ion batteriesas does that same company's Powerwall system which stores energy collected from roof-top solar panels or the grid. Copyright 2019 Ge and Jakobsson. Lithium Chloride Promotes Apoptosis in Human Leukemia NB4 Cells by Inhibiting Glycogen Synthase Kinase-3 Beta. Visual representation of mutual enrichment patterns between specific cancer pathways and the interactomes of lithium-sensitive gene products. A molecular model for lithium's bioactive form. 2011;16(4):452-457. doi:10.1634/theoncologist.2010-0323, Home Virchows Arch. (1998) 15:326. J Membr Biol. (2013) 23:361. doi: 10.1097/IGC.0b013e31827cfecb, 14. Avissar S, Murphy DL, Schreiber G. Magnesium reversal of lithium inhibition of -adrenergic and muscarinic receptor coupling to G proteins. (2001) 41:789813. At the other end of the dosage scale, epidemiological evidence is compelling that geographical variations in concentration of lithium in the drinking water are correlated with a variety of health and wellness markers, most notably and reliably with incidence of suicide (6469). There is currently no definitive answer to whether or not lithium batteries can cause cancer. A recent story in Harper's Bazaar looks into the claims. "What we are worried about at the moment is the fact there is very little regulation regarding lithium-ion batteries and the safety aspect associated with that," Dr. Priestley says. And even when a lithium-ion battery fire appears to have been extinguished, it can reignite hoursor sometimes even dayslater. (2014) 5:43442. The archaeal enzyme has high homology (30% identical, 50% similar) to its human counterpart and functions in the same magnesium-dependent manner.