1996 Fiscal Year Final Research Report Summary
Pathophisiological study of acinar cell proliferation and apoptosis
| Project/Area Number |
08670609
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
KASHIMA Kei Kyoto Prefectural University of Medicine, Department of Internal Medicine, Professor, 医学部, 教授 (30079818)
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| Co-Investigator(Kenkyū-buntansha) |
KATAOKA Keisho Kyoto Prefectural University of Medicine, Department of Internal Medicine, Assis, 医学部, 助手 (70185792)
SAKAGAMI Junichi Kyoto Prefectural University of Medicine, Department of Internal Medicine, Resea
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| Project Period (FY) |
1996 – 1997
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| Keywords | Proliferation / Apoptosis / CCK / PCNA / BrdU / Cell cycle / Western blot / Cyclin D_1 |
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| Research Abstract |
We investigated acinar cell proliferation and apoptosis during the pancreatic reconstruction after acinar hyperplasia or acute pancreatitis. We applied two different experimental models as camostat-induced pancreatic hyperplasia and as arginine-induced acute pancreatitis in rats. Plasma cholecystokinin (CCK) reached the highest peak at 30 min after single oral administration of camostat (50mg/kg BW) and gradually declined to control level by 9 hrs. Pancreatic DNA content significantly increased at 1 day affer camostat administration. Pancreatic wet weight, protein content, and RNA content significantly increased at day 2, all of which described above decreased to control level by day 5. In this model, we can estimate both pancreatic trophism and involution. BrdU labeling indices (LI) of acinar cells markedly increased at day 1, thereafter rapidly decreased. On the other hand, TUNEL-positive acinar cells significantly increased during day 1 to day 5. Observed number of acini possessing
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both BrdU-positive cell and apoptotic cell were significantly low compared to expected number of acini calculated by using binominal distribution (p<0.001) or Poisson's distribution (p<0.001). We administered BrdU (4mg/hr) to conscious rats intravenously during 12 to 36 hrs after camostat administration when the DNA synthesis of acinar cell is prominent. These animals were killed at day 5. Approximately 12% of acinar cells were labeled with BrdU and were seemed to exist focally. We also observed BrdU-positive mitosis which indicates acinar cell is able to replicate at least twice. Acute pancreatitis was made by single administration of L-arginine monohydrochloride (4.5g/kg BW) intraperitoneally. At 12 hrs after induction of acute pancreatitis, PCNA-positive acinar cells markedly increased, Whereas the BrdU LI remained low level. PCNA is known as a nuclear protein that shows striking increase during late G_1 through S phase of cell cycle. Therefor, we suspect that acinar cell death during the progressing phase of pancreatitis occurs subsequent to entering G_1 phase. The results of western blotting indicated that augmented PCNA of acinar cell during the progressing phase of pancreatitis exists as polymeric structure or as complex consistent with G_1 cyclins (e.g.cyclin D_1). During the regenerative period of acute pancreatitis. acinar cell apoptosis as well as proliferation significantly increased. Similar to the resu of our first experiment, Observed number of acini possessing both BrdU-positive cell and apoptotic cell were significantly low compared to expected number of acini calculated by using binominal distribution (p<0.0001) or Poisson's distribution (p<0.0001). Although a cinar cell proliferation and apoptosis occurs at random when searched for separately, these might be spatially controlled as acinar unit Less
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