Heiko Bugger

Home Institution
Albert-Ludwigs-Universität Freiburg i. Br.

Host Institution
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven
Research Mentor: Raymond R. Russell III, M.D., Ph.D.

E-mail: heiko.bugger@gmx.net

Research Topic
see Abstract
Personal Reactions to the U.S. Experience
Many people readily say that Americans have no culture, maybe because of the country's short history compared to all the European countries. But I think there is definitely an own culture that developed in this country. That not only includes different food and the way Americans enjoy their meals, it is also the way people talk to each other, how Americans think about things like world policy and domestic issues and how they manage their everyday lives. It is quite different from what I know from my home country. And that is an experience I never want to miss, because I learned to see things from another point of view, and I will change my mind about some things in Germany when I return home.
Greatest Difficulties Encountered
Getting to Stop and Shop was always a problem because this food store was outside the city, as are all the big shops and markets. I was not able to afford my own car, so I had to arrange rides with friends who could afford a car, and that required a lot of flexibility.
Most humorous incident
It is difficult to emphasize one thing that was most humorous because there were so many small things every day that happened that were just different and therefore just funny. Riding a bicycle in the US was a real adventure because nobody took care of you, no pedestrian, no car and also no police officer. That made it a life-defending job to ride my bike safely and caused quite a few unexpected and funny situations.
Helpful Hints for Future Students
- Save some money before your trip. You will need it.
- Make sure you have a working credit card.
- Attend the BMEP FORUM in Maine.
- Never try Budweiser!

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Abstract on Research Topic
Downregulation of uncoupling proteins 2 and 3 in the failing heart: Effects on energy metabolism and reactive oxygen species generation
Authors
Heiko Bugger, Cinthia Guzman, Christoph Zechner, Monica Palmeri, Kerry S. Russell, Raymond R. Russell III
Institution
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT
Purpose
Uncoupling protein (UCP)-2 and UCP-3 are mitochondrial proteins responsible for dissipating the proton gradient across the inner mitochondrial membrane and therefore ultimately regulate coupling between citric acid cycle flux and ATP synthesis. UCP-2 and UCP-3 are also thought to regulate fatty acid metabolism and detoxify mitochondrial reactive oxygen species (ROS). Recent studies have demonstrated that heart failure decreases UCP-2 and UCP-3 mRNA expression. However, the expression of UCP-2 and UCP-3 protein in the failing heart and the resultant changes in mitochondrial function have not been determined.
Methods and Results
Heart failure was induced in rats with doxorubicin (18mg/kg total). There was an associated 60% decrease in UCP-2 and UCP-3 expression in hearts from doxorubicin-treated rats compared to nonfailing hearts. In order to determine the effects of decreased UCP expression, respiration and ATP synthesis were determined for isolated mitochondria. While the rates of state 3 and state 4 respiration and ATP synthesis were lower in mitochondria from failing hearts, the respiratory control ratio (RCR) was 15% higher and the ratio of ATP production to oxygen consumption (P/O ratio) was 25% higher in mitochondria from failing hearts, indicating greater coupling between citric acid cycle flux and mitochondrial ATP synthesis. In contrast to the beneficial effects on ATP synthesis, downregulation of UCP-2 and UCP-3 in the failing heart resulted in greater ROS generation.

Conclusion
In the failing heart, the downregulation of UCP-2 and UCP-3 improves the efficiency of ATP synthesis, partially compensating for abnormal energy metabolism. However, the beneficial effect is counterbalanced by a decreased ability to detoxify ROS.

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