October 2009

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

As described previously,  anti-oxidants from unusual sources (hydrogen sulfide, rotten egg gas) may be helpful in reducing the damage caused by heart attacks and strokes.  The use of hydrogen sulfide produced by the human body as an anti-oxidant illustrates the great lengths we will go to protect ourselves against injury.   A recent study (https://www.sciencemag.org/cgi/content/full/325/5946/1380) published in Science magazine shows that some bacteria are also smart enough to use self produced anti-oxidants to protect them against injury caused by antibiotic drugs.

Nitric Oxide molecule

Nitric Oxide molecule

Nitric oxide (NO) is produced by an enzyme called nitric oxide synthase (NOS).  NOS uses the amino acid L-arginine as the precursor for NO production.  NO is used as a signaling molecule in the nervous system, in blood vessels and by immune cells that use NO to kill invading organisms.  It seems that some bacteria also have their own version of NOS called bacterial NOS (bNOS) that  produces NO from L-arginine.  In addition to its’ role as a signaling molecule in the nervous, cardiovascular and immune systems, NO can act as an anti-oxidant.  NO combines with oxygen radicals reducing the injury that these radicals can cause to cells and tissues.

Nitric Oxide structure (Nitric Oxide at the Chemical Database)

Nitric Oxide structure (Nitric Oxide at the Chemical Database)

What is interesting about bNOS is that many antibiotic drugs kill bacteria by producing oxygen radicals.  Different kinds of bacteria also live in competition with one another.  Bacteria compete for nutrients, and eliminating the competition helps one kind of bacteria survive – at the expense of other bacteria.  Bacteria can generate oxygen radicals to kill off their competitors.  However, the targets of these oxygen radicals have evolved their own anti-oxidant protective mechanism in the form of bNOS and NO production.  NO interacts with oxygen radicals produced by antibiotics and by other bacteria.  This interaction inactivates the oxygen radicals protecting the bacteria against these toxic chemicals.

This is a very interesting study of the biology of bacteria and their interaction with their environment.  The study also provides new insights into how we might best attack bacteria that infect humans, animals and plants.  Perhaps in addition to conventional antibiotic drugs, we could add on an inhibitor of bNOS removing their protection against oxygen radicals.  Treatments for human disease can come from the most unexpected places.  Basic research comes to the rescue again.

Dr. Mark Roth

Dr. Mark Roth

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

You may have seen a recent news article about near death experiences on CNN.  Associated with this report was a story about the potential life saving effects of the supposedly toxic gas, hydrogen sulfide (H2S).  This is the gas that gives rotten eggs their characteristic smell and it was long thought that H2S was not only foul smelling but a deadly gas.  However, the CNN story goes on to discuss the work of Dr. Mark Roth who is studying the potentially protective and life saving effects of H2S.

Dr. Roth has shown in laboratory animals that H2S may protect cells and tissues against the toxic effects of ischemia (low oxygen supply to tissues and cells).  Ischemica occurs during a heart attack or stroke which block blood flow to the heart or brain respectively.  H2S may protect cells against the dangerous chemical reactions that occur in cells when their oxygen supply is reduced.

Hydrogen Sulfide 3d

Hydrogen Sulfide 3d

This is an interesting story as it highlights a potential function of one of the so-called gasotransmitters that are synthesized in cells of animals and humans.  These gasotransmitters include nitric oxide (NO) (not to be confused with nitrous oxide, “Laughing gas”), carbon monoxide (CO) (yes, the carbon monoxide that is the toxic component of automobile exhaust and the carbon monoxide detected by your in home carbon monoxide detector) and H2S.

NO is produced by the enzyme nitric oxide synthase and NO is produced in the nervous system, in blood vessels and by immune cells.  NO functions as a neurotransmitter in the brain and in the gastrointestinal tract.  NO also relaxes blood vessels to increase blood flow to tissues and it is released by immune cells as part of their defense mechanism against invading bacteria and viruses.

CO is produced by the enzyme heme oxygenase (HO) and CO is also a signaling molecule in the brain, the gastrointestinal tract and in blood vessels.  H2S is produced by three different enzymes: cystathionine-b-synthase (CBS), cystathionine-g-lyase (CGL), and 3-mercaptopyruvate sulfurtransferase (3MST).  H2S is also a signaling molecule in the brain, gut and blood vessels.  H2S is an antioxidant that reduces levels of the dangerous oxygen radicals that are paradoxically produced during ischemia and particularly during reperfusion of tissues when the blood supply is restored.  The oxygen radicals activate apoptosis (the programmed cell death mechanism) that is responsible for the permanent tissue injury that occurs during ischemia and subsequent reperfusion.  H2S may act as an endogenous anti-oxidant but, as Dr. Roth’s work has shown, exogenous H2S may also be a good anti-oxidant.

This story also points out the importance of basic research.  No one would have predicted that the foul smelling and toxic rotten egg gas would have the potential to be a life saving treatment.  However, basic laboratory science revealed the complexity of the H2S system and how its activation could protect tissues against ischemic injury.  The emerging H2S story is another example of how new drugs or other treatments for human disease can come from the most unlikely sources.

Dept of Pharm/Tox logo

posted by Nathan Tykocki, current Graduate Student

Pharmacology and Toxicology are unique disciplines, in that they integrate the methods and techniques of nearly all the Biological Sciences to reach a common goal: to explain how substances interact with a living system to cause a response.  Our training may be in molecular biology, genetics, physiology or microbiology, but we Pharmacologists and Toxicologists integrate all of these strategies to understand ‘how we tick’.  We are a truly unique group of scientists;  and graduates from Michigan State University’s Pharmacology and Toxicology department are no exception.

The diverse academic and research applications of Pharmacology and Toxicology mean that our graduates have taken flight far from MSU’s ivy-covered halls.  We have moved to be clinician/scientists, biomedical researchers, teachers, academics, and national thought-leaders.  However, while our branches have spread thousands of miles, our roots will always be at Michigan State University.  For us all, our careers began right here – where we learned the value of good, careful research and the confidence to investigate the unknown.

During the week of Michigan State University’s Homecoming, I am reminded that there truly is “no place like home”. While many years may have passed since our graduates opened the door to the Life Sciences Building, our department wants to open its doors to you once again.  On Saturday, October 17th from 9 am to Noon, MSU’s department of Pharmacology and Toxicology is hosting an Alumni Reception and Tailgate outside of the Life Sciences Building.  We ask all of you to join us as we thank you for all the hard work that you gave to make us what we are, and let us show you where we are going in the future!

More information on the event can be found at http://phmtox.msu.edu, or please contact Diane Hummel (517/353-9616) to RSVP.

We hope to see you all homecoming weekend; to show you how your home has grown, and enjoy the company of our friends, new and old.

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