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When Heme Attacks: After Trauma, The Molecule That Makes Life Possible Rampages

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    When Heme Attacks: After Trauma, The Molecule That Makes Life Possible Rampages

    When Heme Attacks: After Trauma, The Molecule That Makes Life Possible Rampages
    Philadelphia, PA -- Heme, the iron-bearing, oxygen-carrying core of hemoglobin, makes it possible for blood to carry oxygen, but researchers from the University of Pennsylvania School of Medicine have determined how free-floating heme can also make traumatic events worse by damaging tissue. The Penn researchers present their findings in the October 2nd issue of the journal Nature. Fortunately, the researchers also identified a chemical that can be targeted by drug developers to impede the deleterious effects of free-floating heme.

    Following a traumatic event - such as an accident, a stroke, a heart attack or even surgery - heme floods the spaces between and inside cells and exacerbates the damage. It does so by shutting down an important cell membrane channel, an action that kills neurons and constricts blood vessels. While investigating this process, the researchers also determined that a chemical called NS1619 restores the function of the cell membrane channel. NS1619 and its derivatives could be the source for a new drug - one that prevents the secondary events that worsen trauma damage.

    "Following a heart attack, a stroke, or any really severe physical injury, heme is literally shaken loose from hemoglobin," said Xiang Dong Tang, MD, PhD, Staff Scientist in Penn's Department of Physiology. "Normally, cells can compensate and recycle loose heme. But when larger concentrations are released, heme can gum up the works, specifically the Maxi-K ion channel, a cell membrane protein important for blood vessel relaxation and neuron excitability."

    Maxi-K is a channel that moves potassium ions out of cells. In the Nature paper, Tang and his colleagues prove that the Maxi-K protein possesses sites that bind heme. If these sites were removed or altered, heme could not effect Maxi-K proteins.

    "Maxi-K is found in the lining of blood vessels. When it is turned off, the vessel constricts, increasing blood pressure, which is decidedly not beneficial following a heart attack, " said Toshinori Hoshi, PhD, Associate Professor in Penn's Department of Physiology and co-author of the Nature article. "In neurons, disrupting Maxi-K leads to excessive calcium accumulation. Eventually, this ionic buildup triggers cell suicide and, therefore, the loss of the neuron."

    The chemical heme is essential for most forms of life. It exists in hemoglobin for oxygen transport, in cytochromes for cellular energy production, and in guanylate cyclase for blood pressure regulation. The molecule itself is tiny, a flat snowflake of a carbon framework surrounding a single atom of iron, but it is crucial for the cellular process of respiration and the action of nirtroglycerine.

    "Generally, the heme molecule is attached to larger molecules, such as hemoglobin, but it is easily set loose. Indeed, there is an entire cellular industry behind recycling and reusing 'lost' heme," said Tang. "But that system can get overwhelmed in times of serious trauma and bleeding."

    Studying the heme recycling system might prove useful in developing treatments for preventing the secondary damage set off by heme. Certain cells, such as neurons, do have ways of transporting heme. If the 'heme transport' is identified and the specific blocker is found, it could help prevent symptoms resulting from trauma and bleeding.

    Meanwhile, according to Tang and his colleagues, there is already a known agent that can relieve Maxi-K from heme inhibition. NS1619 is known as the "Maxi-K opener," and, as the researchers have shown, readily reverses the heme-mediated inhibition.

    "I can envision the use of a drug similar to NS1619 as an emergency treatment," said Tang. "In the emergency room, after an accident or heart attack, it could be used to keep the damage from continuing on a cellular level - before it could result in bad effects for the entire body."

    Scientists also contributing to this research include Rong Xu from Penn, Mark F. Reynolds, from St. Joseph's University, Marcia L. Garcia, from Merck Research Laboratories, and Stefan H. Heinemann, from Friedrich Schiller University. Funding for this research came from the National Institutes of Health.


    --------------------------------------------------------------------------------

    This story has been adapted from a news release issued by University Of Pennsylvania Medical Center.


    http://www.sciencedaily.com/releases...1002055731.htm
    http://stores.ebay.com/MAKSYM-Variety-Store

    #2
    bump

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      #3
      So...potential for acutes ...let's see where this goes
      "That's not smog! It's SMUG!! " - randy marsh, southpark

      "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


      2010 SCINet Clinical Trial Support Squad Member
      Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

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        #4
        This was posted 17 years ago.
        "I have great faith in fools; self-confidence my friends call it." - Edgar Allen Poe

        "If you only know your side of an issue, you know nothing." -John Stuart Mill, On Liberty

        Comment


        • crabbyshark
          crabbyshark commented
          Editing a comment
          I know. Just because it's 17 years old though doesn't mean it's not relevant. Bear with me.

        #5
        just because it's 17 years old doesn't mean it's not relevant?

        Really...doesn't it though?
        "That's not smog! It's SMUG!! " - randy marsh, southpark

        "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


        2010 SCINet Clinical Trial Support Squad Member
        Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

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          #6
          Originally posted by lunasicc42 View Post
          just because it's 17 years old doesn't mean it's not relevant?

          Really...doesn't it though?
          If heme was found to be a problem 17 years ago, and today still nothing is being done about heme, is heme still a problem or not?

          Comment


          • Oddity
            Oddity commented
            Editing a comment
            See, this makes sense. But a seemingly random "bump" of a 17 year old topic, void of any context, is kinda hard for anyone to interpret or respond to.

          #7
          I was suggesting that this research and therefore; the bumping of this post was irrelevant ...just in a round-about way
          "That's not smog! It's SMUG!! " - randy marsh, southpark

          "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


          2010 SCINet Clinical Trial Support Squad Member
          Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

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            #8
            After spinal cord injury, men's semen appears rust brown.

            Alzheimer's brains also appear "rusty."

            https://www.futurity.org/alzheimers-...ust-1497682-2/

            Hmm

            Comment


              #9
              1. J Neurosci. 2004 Sep 29;24(39):8562-76. doi: 10.1523/JNEUROSCI.3316-04.2004.

              Patterns of gene expression reveal a temporally orchestrated wound healing
              response in the injured spinal cord.


              Velardo MJ(1), Burger C, Williams PR, Baker HV, López MC, Mareci TH, White TE,
              Muzyczka N, Reier PJ.

              Author information:
              (1)Department of Neuroscience, McKnight Brain Institute of the University of
              Florida, Gainesville, Florida 32610-0244, USA. velardo@mbi.ufl.edu

              Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell
              survival and neurological integrity via complex and evolving molecular cascades
              whose interrelationships are not fully understood. The present experiments were
              designed to: (1) determine potential functional interactions within
              transcriptional expression profiles obtained after a clinically relevant SCI and
              (2) test the consistency of transcript expression after SCI in two genetically
              and immunologically diverse rat strains characterized by differences in T cell
              competence and associated inflammatory responses. By interrogating Affymetrix
              U34A rat genome GeneChip microarrays, we defined the transcriptional expression
              patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of
              athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical
              analyses detected significant changes in 3638 probe sets, with 80 genes
              differing between the AN and SD groups. Subsequent detailed functional
              categorization of these transcripts unveiled an overall tissue remodeling
              response that was common to both strains. The functionally organized gene
              profiles were temporally distinct and correlated with repair indices observed
              microscopically and by magnetic resonance microimaging. Our molecular and
              anatomical observations have identified a novel, longitudinal perspective of the
              post-SCI response, namely, that of a highly orchestrated tissue repair and
              remodeling repertoire with a prominent cutaneous wound healing signature that is
              conserved between two widely differing rat strains. These results have
              significant bearing on the continuing development of cellular and
              pharmacological therapeutics directed at tissue rescue and neuronal regeneration
              in the injured spinal cord.

              DOI: 10.1523/JNEUROSCI.3316-04.2004
              PMCID: PMC6729887
              PMID: 15456830 [Indexed for MEDLINE]
              https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729887/

              In the study above, researchers looked at all the genes that were expressed after spinal cord injury in two groups of different kinds of rats. They examined thousands of genes.

              What did they find?

              "Our analysis revealed an intricate postinjury transcriptional response with significant changes in the expression levels of 3638 probe sets that possessed an overall pattern remarkably resembling the molecular events underlying the stages of dermal WH."

              They found that spinal cord tissue and skin tissue heal in nearly the exact same way.

              They called this "remarkable."

              Did you guys know spinal cord tissue and skin tissue heal the same way?

              Do you also find this remarkable?

              Better questions:

              If spinal cord tissue and skin tissue heal almost identically, why does skin tissue almost always get better while spinal cord tissue frequently does not?

              Why is there still an injury site?

              Comment


                #10
                Most spinal cord injuries are spinal cord contusions.

                Contusion is just another name for bruise.

                If we look at how bruises heal, could this show anything about how a bruised spinal cord heals?

                Why bruises change color:

                https://www.youtube.com/watch?v=EOZN4lyWhsI

                A bruise starts off blue then turns green then turns yellow.

                According to the video, the blue is deoxygenated hemoglobin. Hemoglobin is where heme comes from.

                So how is this related to spinal cord injury?

                Go to the Velardo study in the post above this one and zoom all the way in on the spinal cord images in Figure One. You see the black specks on the spinal cords?

                Those specks are NOT supposed to be there.

                The specks are present in both acute and chronic spinal cord injury.

                According the key, the specks represent free heme, clotted blood, and hemorrhage.

                Free heme, like the title of this thread indicates, is highly inflammatory.

                To keep things less confusing, we will just focus on heme for now and address the other stuff later.

                If heme is a problem, how does the body get rid of it? How does a bruise go from blue to green?

                Comment


                  #11
                  On 5 Oct 2003, 1:00 PM I was still an able bodied person

                  Comment

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