Waliaula Mola,P; Sudha, B; Paulose,C S(Department of Biotechnolgy, November , 1996)
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Abstract:
The effect of insulin on cell proliferation in vivo has been studied in hepatectomised
streptozotocin- diabetic rats. The extent of cell proliferation in sham and hepatectomized- control,
diabetic and insulin treated rats were monitored by determining DNA content and [3H]thymidine
incorporation into DNA. The kinetic parameters of thymidine kinase a regulatory enzyme for
DNA synthesis was also studied in these groups. The rate of DNA synthesis in liver of
streptozotocin -diabetic rats was significantly higher 24 hrs post-hepatectomy compared to
control and insulin treated diabetic groups. Kinetic studies of thymidine kinase revealed that there
was no change in the Michaelis -Menten constant (Km) whereas maximum velocity (Vmax) was
elevated in the diabetic hepatectomized groups compared to control and insulin treated
hepatectomized groups. Thus our study elucidates the role of insulin in thymidine kinase activity
and DNA synthesis.
Biju,M P; Pyroja,Sulaiman; Rajeshkumar,Neelimmathara V; Paulose,C S(Department of Biotechnology, February 15, 2001)
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Abstract:
Gamma aminohutyric acid (GAB A.) receptor tunctionaI status was artaIV se(l in pa It ial hcpatcctoIn ised.II'II). lead
nitrate (LN) induced hyperplastic and N-nifrosodiethylantinc INDEAI treated nctplastic rat Iivers during peak DNA
synthesis. The high-affinity I'HJGALA binding significantly decreased in PII and NDEi\ rats and the receptor affinity
decreased in NDEA and increased in LN rats compared with control . in NDEA. displacement analysis of I'I IIGABA
with muscimol showed loss of low-allinity site and a shill of high-allinity cite towards low-allinity . ' 1 he affinity sites
shifted towards high-affinity in LN rats. 'file number of low-allinity 1'I Ilhicuc)lline receptors decreased cignilic:uttly
in NDEA and I'll whereas it increased in LN rats. (ir\Bi\t receptor :gunist. unrscinrul. disc dependcnllyinhihilcd
epidermal growth factor IEGI--) induced DNA synthesis :uul enhanced the tr:utsfnrnting grmvth )actor (Il I I'(il (tlI
mediated DNA synthesis suppression in prim:uy hepalucvte cultures . Our results suggest that GABA,t reccjhtor act
as an inhibitory signal fur hepatic cell prolifctatiun.
Sulaiman,Pyroja; Binoy,Joseph; Paulose,C S(Department of Biotechnology, December 5, 2006)
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Abstract:
In the present study, serotonin 2C (5-HT2c) receptor binding parameters in the brainstem and cerebral cortex were investigated during
liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The
serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem
serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of
the 5-HT2c receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in
NDEA induced hepatic neoplasia. The number and affinity of 5-HT2c receptors increased significantly (p<0.001) in NDEA induced hepatic
neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma
norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that
during active hepatocyte proliferation 5-HT2c receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte
proliferation mediated through sympathetic stimulation.
Tessy,Maliekal T; Sudha, B; Paulose,C S(Department of Biotechnology, February 14, 1997)
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Abstract:
The role of thyroid hormones in DNA synthesis and in the activity of Thymidille
kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating
hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a
model for controlled cell division in rats having different thyroid status - euthyroid,
hypothyroid and 3,3',5'-triiodo-L-thyronine (T))-heated hypothyroid. Partial
hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three
groups compared to their sham-operated counterparts. Hypothyroid liepatectomised
animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid
hepatectomised animals. A single subcutaneous close of 1'3 to hypothyroid shamoperated
animals resulted in a significant increase (p<0.01) of DNA synthesis in the
intact liver. 17tis was comparable to the level of DNA synthesis occurring in
regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, "1'3
showed an additive effect on l)NA synthesis and this group exhibited maximum level
of DNA synthesis (p<0.0I ). Studies of the kinetic parameters of TK show that the
Michelis-Menten constant, (K111) of TK for thymidine was altered by the thyroid
status. K11 increased significantly (p<0.01) in untreated hypothyroid animals when
compared to the euthyroid rats. '13 treatment of hypothyroid animals reversed this
effect and this group showed the lowest value for K111 (p<0.01). Thus our results
indicate that thyroid hormones can influence DNA synthesis during liver regeneration
and they may regulate the activity of enzymes such as 17rymidine kinase which are
important for DNA synthesis and hence cell division.