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Abstract:
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The adult mammalian liver is predominantly in a quiescent state with respect to cell
division. This quiescent state changes dramatically, however, if the liver is injured by
toxic, infectious or mechanic agents (Ponder, 1996). Partial hepatectomy (PH) which
consists of surgical removal of two-thirds of the liver, has been used to stimulate
hepatocyte proliferation (Higgins & Anderson 1931). This experimental model of liver
regeneration has been the target of many studies to probe the mechanisms responsible for
liver cell growth control (Michalopoulos, 1990; Taub, 1996). After PH most of the
remaining cells in the renmant liver respond with co-ordinated waves of DNA synthesis
and divide in a process called compensatory hyperplasia. Hence, liver regeneration is a
model of relatively synchronous cell cycle progression in vivo. In contrast to hepatomas,
cell division is terminated under some intrinsic control when the original cellular mass has
been regained. This has made liver regeneration a useful model to dissect the biochemical
and molecular mechanisms of cell division regulation. The liver is thus, one of the few
adult organs that demonstrates a physiological growth rewonse (Fausto & Mead, 1989;
Fausto & Webber, 1994). The regulation of liver cell proliferation involves circulating or
intrahepatic factors that are involved in either the priming of hepatocytes to enter the cell
cycle (Go to G1) or progression through the cell cycle. In order to understand the basis of
liver regeneration it is mandatory to define the mechanisms which (a) trigger division, (b)
allow the liver to concurrently grow and maintain dilferentiated fimction and (c) terminate
cell proliferation once the liver has reached the appropriate mass. Studies on these aspects
of liver regeneration will provide basic insight of cell growth and dilferentiation, liver
diseases like viral hepatitis, toxic damage and liver transplant where regeneration of the
liver is essential. In the present study, Go/G1/S transition of hepatocytes re-entering the
cell cycle after PH was studied with special emphasis on the involvement of
neurotransmitters, their receptors and second messenger function in the control of cell
division during liver regeneration |