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| Marion
Schölzke |
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Home
Institution
Ruprecht-Karls-Universität Heidelberg
Host
Institution
The Burnham Institute, La Jolla, CA
Mentors:
Stuart A. Lipton, MD, Ph.D.; Ella Bossy-Wetzel, Ph.D.
E-Mail
mschoelz@ix.urz.uni-heidelberg.de
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Research
Topic
see Abstract |
Personal
Reactions to the U.S. Experience
My time here enriched my research experience as well as my personal life.
The lab was a melting pot of all types of cultures and personalities from
many different countries, which made working on a common goal so much more
interesting. Also, outside of the lab I met many Americans from various
backgrounds, which painted a colorful picture of the diversity in American
culture. I was able to get insight into different ways of looking at life
and dealing with problems. This is an experience I am glad not to have missed,
which will be a valuable tool for the rest of my life. |
Greatest
Difficulties Encountered
I had two major difficulties during my stay in San Diego; finding a car
and keeping it running. The latter continues to challenge me. In order to
get around and to have an interesting life in San Diego, you must own a
car. The quality of public transportation is very poor in this city. |
Most
humorous incident
There is not just one most humorous incident; there are so many different
funny stories to tell. But there is one thing I hadn't quite grasped until
now: The ocean moves in unpredictable ways, and, if you don't pay attention
to the water, you will wet your shoes and clothes while walking on the beach.
If you are intelligent enough to take your shoes off when you approach the
water, make sure that the tide is not coming in and that your shoes are
on a rock far enough from the water, or you may see them swimming past you.
My friends and I had a lot to laugh about until we had to fish our shoes
out of the ocean. Now, near the end of my stay in San Diego, I can say that
I do not have a single pair of shoes that have not taken a bath in the Pacific
Ocean. Most of my shoes have enjoyed it several times. |
Helpful
Hints for Future Students
Be open-minded towards everything and everybody. You will come across lots
of things that may seem strange at first sight, but especially these things
can turn out to be very interesting and a lot of fun. I believe that way
you can truly experience the United States. Try not to spend the entire
time in the lab. Make sure to learn something about the people and the country.
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Abstract
on Research Topic:
Molecular Mechanism of NO-Induced Neurotoxicity |
Institution
at which research was done:
The Burnham Institute, La Jolla, CA |
Purpose:
NO is an important mediator in a wide variety of neurodegenerative disease,
for example stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis,
epilepsy and AIDS dementia. Therefore, it is of high interest to determine
the mechanisms by which NO contributes to these degenerative processes.
We were especially interested in the role of intracellular free Zn2+ concentrations,
mitochondrial dysfunction, and p38 activation. All three can be observed
after treatment of cells with S-nitroso-cysteine (SNOC, an external NO donor).
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Materials
and Methods:
As a model I used primary cerebrocortical cultures that we obtained from
the cortex of rat embryos at day 16 of gestation. A cell free model was
obtained by using isolated liver mitochondria from mice. Cell cultures were
treated with SNOC while isolated mitochondria were treated with different
concentrations of Zn2+. I used the cell cultures for live cell imaging as
well as for immunostaining. Both were imaged using a fluorescent deconvolution
microscope. Furthermore, I used the cerebrocortical cells for immunoblotting
using anti phospho-p38 protein antibodies, as well as transient transfection
experiments with p38 expression vector and GFP expression vector.
The isolated mitochondria I used for measurement of mitochondrial membrane
potential (??m) by FACS analysis and measurement of reactive oxygen species
(ROS) by adding Amplex Red plus Horseradish Peroxidase. |
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Results:
After SNOC-treatment of primary neuronal cultures with the use of selective
dyes, we observed:
1. release of Zn2+ from intracellular stores
2. loss in mitochondria membran potential
3. production of ROS due to the Zn2+ release
The results of the phospho-p38 immunoblots suggest that p38 MAP kinase
phosphorylation was rapidly induced in cerebrocortical neurons upon SNOC
exposure. Our results from the FACS analysis indicate a loss of mitochondria
membran potential in response to Zn2+ treatment. The fluorometer experiments
showed that Zn2+ induces an increase of H2O2 from isolated mitochondria.
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Conclusion:
The results obtained by my colleagues and I show that NO triggers the release
of free Zn2+ from intracellular stores of primary cerebrocortical neurons.
At the same time, it leads to p38 MAP Kinase activation.
Free Zn2+, on the other hand, leads to ROS production and a decrease of
mitochondria membran potential, and so leads to mitochondrial dysfunction.
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Papers:
1) Okamoto, S.-I., LI, Z., Ju, C., Schölzke, M. N., Mathews E., Cui, J.,
Salvesen, G. S., Bossy-Wetzel, E., and Lipton, S. A. (2002) Dominant-Interfering
Forms of MEF2 Generated by Caspase Cleavage Contribute to NMDA-Induced Neuronal
Apoptosis. Proc. Natl. Acad. Sci (in press)
2) Talantova, M. V., Lee, D. W., Schölzke, M. N., Götz, T., Mathews, E.,
Harrop, A., Bossy-Wetzel, E., and Lipton, S. A. (2002) Apoptotic Cell Shrinkage:
An Early Event in NO/(ONOO-)-Induced Neuronal Cell Death Mediated by Zn2+,
Mitochondrial Dysfunction, p38 MAP Kinase and Voltage-Gated Potassium Channels
(in preparation) |
