scholarly journals UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells

2019 ◽  
Vol 20 (8) ◽  
pp. 1971 ◽  
Author(s):  
Kimie Nakagawa ◽  
Kiyomi Fujiwara ◽  
Akihiro Nishimura ◽  
Chinami Murakami ◽  
Kanaha Kawamoto ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Apoptotic Cell ◽  
Biological Effects ◽  
Acinar Cells ◽  
Vitamin K2 ◽  
Pancreatic Acinar Cells ◽  
Biosynthetic Enzyme ◽  
Knockout Mouse Model ◽  
Adult Mice

UbiA prenyltransferase domain-containing protein 1 (UBIAD1) is a vitamin K2 biosynthetic enzyme. We previously showed the lethality of this enzyme in UBIAD1 knockout mice during the embryonic stage. However, the biological effects of UBIAD1 deficiency after birth remain unclear. In the present study, we used a tamoxifen-inducible systemic UBIAD1 knockout mouse model to determine the role of UBIAD1 in adult mice. UBIAD1 knockout resulted in the death of the mice within about 60 days of administration of tamoxifen. The pancreas presented with the most prominent abnormality in the tamoxifen-induced UBIAD1 knockout mice. The pancreas was reduced remarkably in size; furthermore, the pancreatic acinar cells disappeared and were replaced by vacuoles. Further analysis revealed that the vacuoles were adipocytes. UBIAD1 deficiency in the pancreatic acinar cells caused an increase in oxidative stress and autophagy, leading to apoptotic cell death in the tamoxifen-induced UBIAD 1 knockout mice. These results indicate that UBIAD1 is essential for maintaining the survival of pancreatic acinar cells in the pancreas.

scholarly journals Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells

2008 ◽  
Vol 181 (7) ◽  
pp. 1065-1072 ◽  
Author(s):  
Daisuke Hashimoto ◽  
Masaki Ohmuraya ◽  
Masahiko Hirota ◽  
Akitsugu Yamamoto ◽  
Koichi Suyama ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Knockout Mice ◽  
Early Stage ◽  
Acinar Cells ◽  
Conditional Knockout ◽  
Pancreatic Acinar Cells ◽  
Trypsinogen Activation ◽  
Conditional Knockout Mice ◽  
Cellular Environment

Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70–77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome.

Phosphoinositide synthesis in desensitized rat pancreatic acinar cells

1995 ◽  
Vol 268 (6) ◽  
pp. G1043-G1050
Author(s):  
J. S. Lods ◽  
B. Rossignol ◽  
C. Dreux ◽  
J. Morisset
Keyword(s):  
Phorbol Ester ◽  
Inositol Trisphosphate ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Basal Rate ◽  
Phosphoinositide Turnover ◽  
Dose Dependent

To help understand the possible role of phosphoinositide turnover in the desensitization process, the availability of phosphatidylinositol 4,5-bisphosphate was investigated in normal and desensitized pancreatic acinar cells treated with carbamylcholine (Cch), caerulein (Cae), and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In control acini, incorporation of [myo-3H]inositol into total phosphoinositides was maximal at 120 min, was Cch and Cae dose dependent, and was insensitive to TPA. Cch stimulation increased the proportion of [myo-3H]inositol incorporated into phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], whereas Cae specifically channeled [myo-3H]inositol incorporation into phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. In the desensitized cells, preexposure to Cch and Cae, but not to TPA, increased the subsequent basal rate of [myo-3H]inositol incorporation into total phosphoinositol (PI) by 66 and 50% above control values. There were no subsequent responses to increasing concentrations of Cch, Cae, and TPA during a second incubation. Desensitization of the pancreatic secretory responses to Cch, Cae, and TPA does not seem to result from a decrease either in total PI or in specific PtdIns(4,5)P2 synthesis, which is needed for inositol trisphosphate and diacylglycerol production.

scholarly journals SEC23B is required for pancreatic acinar cell function in adult mice

2017 ◽  
Vol 28 (15) ◽  
pp. 2146-2154 ◽  
Author(s):  
Rami Khoriaty ◽  
Nancy Vogel ◽  
Mark J. Hoenerhoff ◽  
M. Dolors Sans ◽  
Guojing Zhu ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Function ◽  
Acinar Cells ◽  
Cell Loss ◽  
Normal Function ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Total Protein Content ◽  
Pancreatic Cell ◽  
Adult Mice

Mice with germline absence of SEC23B die perinatally, exhibiting massive pancreatic degeneration. We generated mice with tamoxifen-inducible, pancreatic acinar cell–specific Sec23b deletion. Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in decreased overall pancreatic weights from pancreatic cell loss (decreased pancreatic DNA, RNA, and total protein content), as well as degeneration of exocrine cells, decreased zymogen granules, and alterations in the endoplasmic reticulum (ER), ranging from vesicular ER to markedly expanded cisternae with accumulation of moderate-density content or intracisternal granules. Acinar Sec23b deletion results in induction of ER stress and increased apoptosis in the pancreas, potentially explaining the loss of pancreatic cells and decreased pancreatic weight. These findings demonstrate that SEC23B is required for normal function of pancreatic acinar cells in adult mice.

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