|
http://tinyurl.com/7472a
Posted on Sun, Oct. 09, 2005
More research urged into effects of inorganic mercury
By JUDY L. THOMAS
The Kansas City Star
Researchers and lawmakers worry that not enough is known about ethylmercury, the
kind of mercury in flu vaccines. For years, health officials assumed that
ethylmercury was less toxic to infants than methylmercury, which poses a risk to
pregnant women and is found in some seafood.
A recent study funded by the National Institutes of Health found that while
there was less total mercury in monkeys' brains after injections containing
thimerosal than after exposure to methylmercury in food, there was twice as much
inorganic mercury in the monkeys' brains after the thimerosal injections.
Thimerosal is a compound that is 49.6 percent ethylmercury by weight.
"Having less total mercury in your brain is good news, but having this inorganic
mercury twice as high in your brain is concerning,"said Thomas Burbacher, a
mercury toxicology expert at the University of Washington and the key researcher
on the project. Previous studies had shown that inorganic mercury can inflame
certain kinds of brain cells.
Some scientists and lawmakers say the NIH study shows that more research is
needed. "Clearly, prior assumptions about the way thimerosal is handled by the
human body must be revisited, and follow-up studies must be undertaken," U.S.
Rep. Dave Weldon wrote in April to Michael Leavitt, secretary of health and
human services.
Critics say that some of the studies that were used to show no connection
between thimerosal and autism were done by researchers who were too cozy with
government agencies and drug companies. They also note that some decisions on
vaccine policy were made by advisory boards and that some members of those
boards had ties to drug
companies that would be affected by their decisions.
For example, in a recent congressional hearing, it was revealed that members of
committees that advise the Food and Drug Administration and the Centers for
Disease Control and Prevention owned stock in drug companies that made vaccines.
Committee members also held patents on vaccines affected by the decisions of
their committees.
Some researchers and scientists also complain that when their findings suggested
possible links between thimerosal and autism, government agencies cut off their
funding.
Boyd Haley, a University of Kentucky biochemist, received hundreds of thousands
of dollars in grants from the National Institutes of Health to make compounds
called "photoaffinity probes" that are used to study neurological diseases. "It
was a major scientific accomplishment, and they're used all over the world
today," Haley said. "Our biggest customer is the National Institutes of Health."
But Haley noted that it was "only when I started using these probes to show that
mercury was toxic that I lost my NIH grant, which I had for 27 years."
Weldon said he had heard similar complaints.
"What I've had said to me repeatedly by researchers is that they would start
working on it and they will have their department chairman or their colleagues
"saying, You really shouldn't do this; you're going to ruin your career," Weldon
said. Glen Nowak, the CDC's director of media relations, said he was not aware
of any researchers losing funding as a result of their findings. "At CDC, almost
all the research that we fund is peer reviewed and
it's usually blind peer reviewed," Nowak said. "We don't know who wrote the
proposal. And NIH does this, too. We have objective reviews of the proposals
that come in.To reach Judy L. Thomas, call (816) 234-4334 or send e-mail to
jthomas@kcstar.com . 
Thimerosal Induces Apoptosis in a Neuroblastoma
Model via the cJun N-Terminal Kinase Pathway
http://toxsci.oxfordjournals.org/cgi/content/abstract/92/1/246
Michelle L. Herdman*, Aileen
Marcelo*, Ying Huang ,
Richard M. Niles,
Sanjit Dhar
and Kinsley Kelley Kiningham*,1
Departments of * Pharmacology,
Physiology, and Toxicology and
Biochemistry and
Microbiology, Joan C. Edwards School of Medicine, Marshall
University, Huntington, West Virginia 25704; and
Graduate Center
for Toxicology, University of Kentucky, Lexington, Kentucky 40536
Received January 9, 2006;
accepted April 17, 2006
The cJun N-terminal kinase (JNK)-signaling
pathway is activated in response to a variety of stimuli,
including environmental insults, and has been implicated
in neuronal apoptosis. In this study, we investigated the
role that the JNK pathway plays in neurotoxicity caused
by thimerosal, an ethylmercury-containing preservative.
SK-N-SH cells treated with thimerosal (010΅M) showed an
increase in the phosphorylated (active) form of JNK and
cJun with 5 and 10΅M thimerosal treatment at 2 and 4 h.
To examine activator protein-1 (AP-1) transcription, cells
were transfected with a pGL2 vector containing four AP-1
consensus sequences and then treated with thimerosal
(02.5΅M) for 24 h. Luciferase studies showed an increase
in AP-1 transcriptional activity upon thimerosal
administration. To determine the components of the AP-1
complex, cells were transfected with a dominant negative
to either cFos (A-Fos) or cJun (TAM67). Reporter analysis
showed that TAM67, but not A-Fos, decreased AP-1 transcriptional
activity, indicating a role for cJun in this pathway. To
assess which components are essential to apoptosis, cells
were treated with a cell-permeable JNK inhibitor II
(SP600125)
or transfected with TAM67, and the downstream effectors
of apoptosis were analyzed. Cells pretreated with
SP600125
showed decreases in activation of caspases 9 and 3,
decreases in degradation of poly(ADP-ribose) polymerase (PARP),
and decreased levels of proapoptotic Bim, in comparison
to cells treated with thimerosal alone. However, cells
transfected with TAM67 showed no changes in those same
components. Taken together, these results indicate that
thimerosal-induced neurotoxicity occurs through the JNK-signaling
pathway, independent of cJun activation, leading
ultimately to apoptotic cell death.
Key Words: thimerosal; mercury; neurotoxicity; JNK; cJun;
Bim.
Back to page
|
