X-Message-Number: 28736
Date: Sun, 10 Dec 2006 14:57:47 EST
Subject: Re: Cell death after oxygen restoration

It would be interesting to know if restoring the oxygen very slowly, upping  
the saturation from 0 to 100%, might fail to set this off.
In a message dated 12/9/2006 3:02:47 AM Mountain Standard Time,  

Subject:  Cell Death Following Blood 'Reflow' Injury Tracked To Natura...
Date: Fri,  8 Dec 2006 18:07:22 -0500

Cell Death Following Blood 'Reflow' Injury  Tracked To Natural Toxin
Researchers at Johns Hopkins have discovered what  they believe is the 
"smoking gun" responsible for most tissue and organ  damage after a period of 
blood oxygen loss followed by a sudden  restoration of blood oxygen flow.

Working with mice, the Hopkins team  found that the sudden oxygen bath 
triggered by restored blood flow causes  cells to make a chemical so toxic it 
kills the cells. The work was  published in two papers in the Proceedings of 
the National Academy of  Sciences last week.

Although not sure why it happens, the Hopkins  scientists believe the toxic 
chemical, PAR-polymer, acts like a molecular  sledgehammer, or a death 
switch. "We've found evidence of it in cells  following all types of injury," 
says Ted Dawson, M.D., Ph.D., the Leonard  and Madlyn Abramson Professor of 
Neurodegenerative Diseases, professor of  neurology and co-director of 
Hopkins' Neuroregeneration and Repair Program  in the Institute of Cell 
Engineering (ICE).

The research team has  named the cell death process caused by PAR-polymer 
"parthanatos," after  Thanatos, the personification of death from Greek 

To  establish that PAR-polymer is indeed the culprit in the kind of  
reperfusion injuries long linked to heart attacks, strokes and a variety  of 
blood vessel injuries, the researchers pumped mouse nerve cells full of  
PAR-polymer. The cells died, but to be sure PAR-polymer (and not something  
else) killed them, they examined the brains of mice engineered to lack an  
enzyme that chews up and gets rid of PAR. These mouse brains contained  twice 
as much PAR-polymer as those of normal mice.

After the  researchers induced a blood clot injury like a stroke, the same 
mice  showed a 62 percent increase in the area of brain damage compared to  
normal littermates. Mice that contain more of the PAR-chewing enzyme  
suffered less brain damage than their normal littermates.

To figure  out what triggers the death switch, the researchers tracked 
PAR-polymer's  journey after cells made it. After 15 minutes, PAR-polymer 
hadn't gone  anywhere. But after 30 to 60 minutes, the researchers discovered 
that much  of it traveled right to areas where the switch normally resides.

The  fate of the cell is irreversible once PAR-polymer sets off the trigger,  
says Valina Dawson, Ph.D., professor of neurology, co-director of the  
Neuroregeneration and Repair Program and author of the papers. "If we  could 
figure out how to block PAR-polymer, we could design drugs that  protect the 
switch and prevent cells from dying after heart attacks,  stroke or other 
injuries," she says.

Researchers were supported by  grants from the National Institutes of Health 
and the American Heart  Association.

Authors of the two papers are Shaida Andrabi, No Soo Kim,  Seong Woon Yu, 
Hongmin Wang, David Koh, Masayuki Sasaki, Judith Klaus,  Takatshi Otsuka, 
Zhizheng Zhang, Raymond Koehler, Patricia Hurn, Valina  Dawson and Ted 
Dawson, all of Hopkins, and Guy Poirier of Laval University  Medical Research 
Center at Centre Hospitalier Universitaire de Quebec in  Canada.

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