[tceblog] Neil Fischbein: Peroxisome proliferator-activated receptor agonism and cell signaling

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Posted by Neil Fischbein:
Peroxisome proliferator-activated receptor agonism and cell signaling
http://www.tceblog.com/posts/1147315806.shtml


   [1]This article was made available online yesterday by Environmental
   Health Perspectives. From the abstract [[2]PDF]:

     Trichloroethylene Monograph
     Key Issues in the Role of Peroxisome Proliferator-Activated
     Receptor Agonism and Cell Signaling in Trichloroethylene Toxicity
     Nagalakshmi Keshava and Jane C. Caldwell
     Peroxisome proliferator-activated receptor alpha (PPARa) is thought
     to be involved in several different diseases, toxic responses, and
     receptor pathways. The U.S. Environmental Protection Agencyâs 2001
     draft trichloroethylene (TCE) risk assessment concluded that
     although PPAR may play a role in liver tumor induction, the role of
     its activation and the sequence of subsequent events important to
     tumorogenesis were not well defined, particularly due to
     uncertainties with respect to extraperoxisomal effects. As part of
     a mini-monograph on key issues in the health risk assessment of
     TCE, this article summarizes scientific literature published since
     that time on the effects and actions of PPARa agonism in the
     context of several key scientific questions relevant to TCE risk
     assessment. Recent analyses of the role of PPARa in gene expression
     changes caused by TCE and its metabolites provide only limited data
     for comparison with other PPARa agonists, particularly given the
     difficulties in interpreting results involving PPARa knockout mice.
     Moreover, the increase in data over the last 5 years from the
     broader literature on PPARa agonists presents a more complex array
     of extraperoxisomal effects and actions, suggesting the possibility
     that PPARa may be involved in modes of action (MOAs) not only for
     liver tumors, but also for other effects of TCE and its
     metabolites. In sum, recent studies support the conclusion that the
     human relevance and susceptibility to PPARa-related MOA(s) of
     TCE-induced effects cannot rely on inferences regarding peroxisome
     proliferation per se, and require a better understanding of the
     interplay of extraperoxisomal events following PPARa agonism.

   Download the full version here [[3]PDF]

References

   1. http://www.ehponline.org/docs/2006/8693/abstract.html
   2. http://www.ehponline.org/docs/2006/8693/abstract.pdf
   3. http://www.ehponline.org/members/2006/8693/8693.pdf