Biology Reference
In-Depth Information
Chapter 20
The Knowledge Uncertainty Principle
in Biomedical Sciences
According to the Knowledge Uncertainty Principle described in Sect.
5.2.7
,
all knowledge is uncertain (including physical, chemical, biological, mathematical,
pharmacological, toxicological, medical, and philosophical knowledge), which
agrees with the views expressed by many thinkers throughout the ages (Sect.
A knowledge with S
K
¼
0 is 100% certain,
which is thought to be beyond human capacity as indicated by Inequality
5.26
.
A knowledge has been defined as
the ability to answer a question or solve a
problem
(Sect.
5.2.7
). These ideas will be illustrated using the Nrf2 signaling
pathway in toxicology as an example.
1 is least certain and that with S
K
¼
20.1 The Toxicological Uncertainty Principle (TUP)
Many drugs (e.g., acetaminophen or Tylenol
®
), dietary components (e.g., 6-
(methylsulfinyl)-hexyl isothiocyanate or 6-HITC from Japanese horseradish
wasabi
), and environmental chemicals and radiations (e.g., ozone, UV light) can
generate reactive oxygen and nitrogen species inside the cell. When cells are
exposed to such pro-oxidants, they respond to counteract the effects of the resulting
oxidative stress by activating
self-defense mechanisms
, including the Nrf2 signaling
pathway shown n Fig.
20.1
. The mechanism of the Nrf2-mediated self-defense has
been well worked out in recent years (Surh 2003; Nguyen et al. 2009; Kundu and
Suhr 2010).
The Nrf2 (nuclear factor erythroid-2-related factor-2) (see nodes 8 and 10 in
Fig.
20.1
) is a transcription factor that plays a major role in regulating the expression
of the genes encoding many cytoprotective enzymes (see nodes 20-24) in response
to oxidative stress. It is normally bound to the Kelch-like-ECH-associated protein 1
(Keap1) (see nodes 7 and 9) which confines Nrf2 to the cytosol and prevents it from
being translocated to the nucleus. Keap1 contains many cysteine residues (see SH on
