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

Kimie Nakagawa, Kiyomi Fujiwara, Akihiro Nishimura, Chinami Murakami, Kanaha Kawamoto, Chihiro Ichinose, Yumi Kunitou, Yoshitomo Suhara, Toshio Okano, Hiroshi Hasegawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number8
DOIs
Publication statusPublished - 2019 Apr 22

Fingerprint

Dimethylallyltranstransferase
knockout mice
proteins
Proteins
cells
Tamoxifen
pancreas
death
mice
enzymes
Enzymes
lethality
Vitamin K 2
vitamins
Oxidative stress
biological effects
Vitamins
abnormalities
Cell death

Keywords

  • acinar cells
  • knockout mice
  • MK-4
  • pancreas
  • tamoxifen
  • UBIAD1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Nakagawa, K., Fujiwara, K., Nishimura, A., Murakami, C., Kawamoto, K., Ichinose, C., ... Hasegawa, H. (2019). UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells. International journal of molecular sciences, 20(8). https://doi.org/10.3390/ijms20081971

UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells. / Nakagawa, Kimie; Fujiwara, Kiyomi; Nishimura, Akihiro; Murakami, Chinami; Kawamoto, Kanaha; Ichinose, Chihiro; Kunitou, Yumi; Suhara, Yoshitomo; Okano, Toshio; Hasegawa, Hiroshi.

In: International journal of molecular sciences, Vol. 20, No. 8, 22.04.2019.

Research output: Contribution to journalArticle

Nakagawa, K, Fujiwara, K, Nishimura, A, Murakami, C, Kawamoto, K, Ichinose, C, Kunitou, Y, Suhara, Y, Okano, T & Hasegawa, H 2019, 'UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells', International journal of molecular sciences, vol. 20, no. 8. https://doi.org/10.3390/ijms20081971
Nakagawa K, Fujiwara K, Nishimura A, Murakami C, Kawamoto K, Ichinose C et al. UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells. International journal of molecular sciences. 2019 Apr 22;20(8). https://doi.org/10.3390/ijms20081971
Nakagawa, Kimie ; Fujiwara, Kiyomi ; Nishimura, Akihiro ; Murakami, Chinami ; Kawamoto, Kanaha ; Ichinose, Chihiro ; Kunitou, Yumi ; Suhara, Yoshitomo ; Okano, Toshio ; Hasegawa, Hiroshi. / UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 8.
@article{0353cda455b949889d12fba5745e5273,
title = "UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells",
abstract = "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.",
keywords = "acinar cells, knockout mice, MK-4, pancreas, tamoxifen, UBIAD1",
author = "Kimie Nakagawa and Kiyomi Fujiwara and Akihiro Nishimura and Chinami Murakami and Kanaha Kawamoto and Chihiro Ichinose and Yumi Kunitou and Yoshitomo Suhara and Toshio Okano and Hiroshi Hasegawa",
year = "2019",
month = "4",
day = "22",
doi = "10.3390/ijms20081971",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",

}

TY - JOUR

T1 - UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells

AU - Nakagawa, Kimie

AU - Fujiwara, Kiyomi

AU - Nishimura, Akihiro

AU - Murakami, Chinami

AU - Kawamoto, Kanaha

AU - Ichinose, Chihiro

AU - Kunitou, Yumi

AU - Suhara, Yoshitomo

AU - Okano, Toshio

AU - Hasegawa, Hiroshi

PY - 2019/4/22

Y1 - 2019/4/22

N2 - 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.

AB - 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.

KW - acinar cells

KW - knockout mice

KW - MK-4

KW - pancreas

KW - tamoxifen

KW - UBIAD1

UR - http://www.scopus.com/inward/record.url?scp=85065310192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065310192&partnerID=8YFLogxK

U2 - 10.3390/ijms20081971

DO - 10.3390/ijms20081971

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 8

ER -