1. Introduction
AMP-activated protein kinase
(AMPK) is a protein made up of three subunits α, β and γ,
which controls cellular metabolism. When AMPK is activated, it phosphorylates
the aimed proteins and modifies their functions, thus leading to the process of
energy formation and suppression of energy usage processes 1.
In addition,
AMPK controls tight junction assembly and ion transport 2–4. CFTR channel
function will be inhibited when AMPK phosphorylates CFTR Cl- channel5.
AMPK activators
delay the growth of colorectal cancer (CRC) cell lines and prohibited
colitis-associated carcinogenesis by caspase-3 cleavage6–8. AMPK is
suggested to be used as a drug for CRC chemoprevention since, it’s activation
in intestinal tissues of humans is related to CRC patients9.
Chitosan
oligosaccharide (COS) is the major degradation product of chitin involving
deacetylation process. Because of its characteristics, COS is used as food
supplements10 . However, COS
involves anti-oxidative, anti- inflammatory and anti- bacterial activities10. When COS is
ingested, it will be absorbed by the intestinal epithelium11,12.Till now,
there’s no clear relation of the effect of COS on AMPK 13. In addition,
COS have a major effect on treating secretory diarrheas and chemoprevention of
CRC.
2. Results
2.1. The
average molecular weight (MW) of COS that effects the activity of AMPK is 5000
Da, that increases AMPK activating impacts and examine its potential activity.
2.2.
Western blot analysis is used to describe the impact of COS in T84 cells.
Results show that AMPK phosphorylation and ACC phosphorylation were stimulated
by COS. And the effect of COS on phosphorulation of AMPK was examined on both
HT-29 and Caco-2 cells. These cells need more time than T84 cells to show the
effects.
2.3. COS
don’t require energy to activate AMPK in T84 cells but, it involves CaMKKβ.
2.4. Ca2+
is emitted from intracellular sources so treating with intracellular Ca2+
chelator BAPTA leads to increasing in [Ca2+]i by COS.
2.5. COS
activates AMPK by promoting Ca2+ releasing from mitochondria and
endoplasmic reticlium(ER).
2.6.
Extracellular Ca2+ promotes tight junction assembly that is boosted
by COS through AMPK-dependent mechanism.
2.7. Nuclear
factor kappa B (NF-ĸB) mediated inflammatory is inhibited by COS but it’s distinct
from AMPK in T84.
2.8. In
vivo, COS activates AMPK in intestinal tissues and in the treatment of scretory
diharrheas and chemoprevention of CRC in mice.
3. Discussion
Chitosan oligosaccharides
(COS) that are originated from chitin, are the most abundant carbohydrate
polymers. COS activates AMPK, so this supports tight junction assembly in IEC.
In addition, the absorption of COS activates AMPK in intestinal tissues in vivo
and prevents the secretion of intestinal fluid in secretory diarrheas and
precancerous development of CRC in mice. The average MW that effects AMPK
activation is 5000 Da since, the low MW COS has anti-inflammatory activity with
high effect, and also it has minimized toxicity and a great biocompatibility14. Furthermore, Ca2+ that is released from both
mitochondria and ER, is involve in increasing [Ca2+]i and
activating AMPK. Also, COS may inhibits NF-ĸB-mediated inflammatory
responses by AMPK-independent mechanism. Moreover, AMPK activation is used in
the treatment of hypertension, dyslpidemia, atherosclerosis and Alzheimer’s
disease 5,7,15–18.
In
conclusion, this study shows the helpful usage of COS in the treatment of both
secretory diarrheas and
chemoprevention of CRC and setup a new information’s about the useful
consequences of COS.
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