{"540511":{"#nid":"540511","#data":{"type":"news","title":"Heme, a Poisonous Nutrient, Tracked by \u2018Green Lantern\u2019 Sensor","body":[{"value":"\u003Cp\u003EA pinch of poison can be good for a body, at least if it\u2019s heme.\u003C\/p\u003E\u003Cp\u003EIn minuscule amounts, it works in cells as an essential catalyst called a cofactor and as a signaling molecule to trigger other processes. Now, for the first known time, researchers have tracked those activities inside of cells.\u003C\/p\u003E\u003Cp\u003EBut too high of a concentration is toxic.\u003C\/p\u003E\u003Cp\u003E\u201cPoor heme management can cause things like Alzheimer\u2019s, heart disease, and some types of cancers, so cells have to do a good job of managing how much heme is available,\u201d said Amit Reddi, a biochemist and assistant professor at the Georgia Institute of Technology. \u201cBy having biosensors that can monitor heme in cells, we have this new window into how cells make this essential toxin available in carefully sparse concentrations,\u201d he said.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003E\u2018Heme\u2019 as in \u2018hemoglobin\u2019\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EPeople may recognize heme from its role at the core of hemoglobin, the component of red blood cells responsible for transporting oxygen. The ionic iron in the heme molecule is what attracts the oxygen\u0026nbsp;molecule.\u003C\/p\u003E\u003Cp\u003EIn hemoglobin, the heme is embedded tightly in protein, rendering it non-toxic. Many scientists have long assumed that heme, even in other cells, is basically always static, held tight by the proteins it works with.\u003C\/p\u003E\u003Cp\u003EBut the researchers\u2019 results shatter that assumption.\u003C\/p\u003E\u003Cp\u003EThey published their findings in the journal\u0026nbsp;\u003Ca href=\u0022http:\/\/www.pnas.org\/lookup\/doi\/10.1073\/pnas.1523802113\u0022 target=\u0022_blank\u0022\u003EProceedings of the National Academy of Sciences, on May, 30, 2016\u003C\/a\u003E. \u0026nbsp;Their research is funded by the National Science Foundation and the National Institutes of Health.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMisconception dispelled?\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EWorking with baker\u2019s yeast cells, which, like human cells, are eukaryotes, the researchers observed heme being freed up to float around and participate in life processes.\u003C\/p\u003E\u003Cp\u003E\u201cI think that we have possibly put a misconception to rest,\u201d said lead researcher David Hanna, a graduate student at at the School of Chemistry and Biochemistry and Parker Petit Institute for Bioengineering and Biosciences, where Reddi also researches.\u003C\/p\u003E\u003Cp\u003EHe was expecting to observe a pool of free, or \u201clabile,\u201d heme in the cells, and he did. \u201cA lot of scientists believe in these fixed bonds, that all heme is tied up and buried inside proteins, but there are processes going on that defy that notion that they haven\u2019t been able to explain.\u201d\u003C\/p\u003E\u003Cp\u003ENow the research team lead by Hanna and Reddi can explain some of them via the labile heme pool. \u201cNo one\u2019s shown this before. We have demonstrated that there is a pool of heme that increases and decreases. We\u2019ve shown that there is an exchangeable pool of heme.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EPotentially hazardous nutrient \u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe labile heme serves as a nutrient instead of a poison. But to make sure things stay that way, heme needs to be carefully trafficked through the cell, Reddi said.\u003C\/p\u003E\u003Cp\u003EThe research team designed a fluorescent sensor molecule to keep tabs on that. With heme at very low baseline levels, the sensor lit up bright green, then as heme concentration increased, it caused the light to fade out.\u003C\/p\u003E\u003Cp\u003EUsing the heme sensors, Georgia Tech graduate student Osiris Martinez-Guzman found an enzyme, GAPDH, known for its involvement in breaking down sugar, that the team observed helping buffer cellular labile heme (iron protoporphyrin IX), which got\u0026nbsp;tied up in proteins, leaving only a limited amount free for biochemical reactions.\u003C\/p\u003E\u003Cp\u003EWhen more labile heme is needed, nitric oxide, a signaling molecule, rapidly released heme from entangling proteins, so it could do jobs such as regulating gene expression.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003E\u2018Green Lantern\u2019 glow \u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u201cIf you increase nitric oxide, you see the green glowing sensor dim as the heme becomes labile then the glow brightens back up over time as heme gets bound up again,\u201d Reddi said.\u003C\/p\u003E\u003Cp\u003ENot having a sensor was one reason labile heme has not been previously observed, so the Georgia Tech researchers used a ratiometric fluorescence approach to design one that could be described a little like the comic book superhero \u201cGreen Lantern.\u201d\u003C\/p\u003E\u003Cp\u003EAs hemes are attracted to him like, say, fans, they become clutter, said Reddi, the paper\u2019s principal investigator. \u201cHe holds them in front of his green light, and they block it, making it appear dimmer.\u201d\u003C\/p\u003E\u003Cp\u003E\u201cRatiometric fluorescent techniques have been around for a while, but our technique is new, because it specifically senses heme,\u201d Reddi said. \u201cWe took a heme binding protein from bacteria and clipped it onto to green fluorescent protein.\u201d\u003C\/p\u003E\u003Cp\u003EThe researchers used a blue laser to charge up the lamp part of the sensor protein pair like a glow-in-the-dark sticker, then it re-emitted the green light. \u201cYou see this green image disappearing and reappearing depending on how much heme is available,\u201d Reddi said. \u201cYou can see what\u2019s happening in real time.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003ERaven M. Harvey, Osiris Martinez-Guzman, Bindu Chandrasekharan and Gheevarghese Raju from Georgia Tech; Xiaojing Yuan, Iqbal Hamza from the University of Maryland, and F. Wayne Outten from the University of South Carolina coauthored the paper. The National Science Foundation funded the research under CAREER Award MCB 1552791, and the National Institutes of Health\u2019s National Institute of Environmental Health Sciences funded it under grant number ES025661.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EAny opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003E177 North Avenue\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EAtlanta, Georgia \u0026nbsp;30332-0181 \u0026nbsp;USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts:\u0026nbsp;\u003C\/strong\u003EBen Brumfield (\u003Ca href=\u0022mailto:ben.brumfield@comm.gatech.edu\u0022\u003Eben.brumfield@comm.gatech.edu\u003C\/a\u003E) (404-660-1408) or John Toon (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) (404-894-6986)\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter:\u003C\/strong\u003E\u0026nbsp;Ben Brumfield\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Labile heme\u0027s movements illuminated for the first known time thanks to ratiometric sensor"}],"field_summary":[{"value":"\u003Cp\u003EThe toxin heme is essential to life, but cells must make use of it sparingly and carefully, as poor heme management can lead to Alzheimer\u0027s, heart disease and cancer. Researchers at the Georgia Institute of Technology\u0026nbsp;tailored ratiometric sensors to tracks heme\u0027s movements in yeast cells for the first known time.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Tracking heme has dispelled a widely held assumption that it does not float freely in cellular pools."}],"uid":"31759","created_gmt":"2016-05-26 13:57:51","changed_gmt":"2016-10-08 03:21:49","author":"Ben Brumfield","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-05-30T00:00:00-04:00","iso_date":"2016-05-30T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"540631":{"id":"540631","type":"image","title":"Baker\u0027s yeast cell lights up green","body":null,"created":"1464710400","gmt_created":"2016-05-31 16:00:00","changed":"1475895329","gmt_changed":"2016-10-08 02:55:29","alt":"Baker\u0027s yeast cell lights up 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