Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes

Mako Toyoda, Akira Kitaoka, Kazuyuki Machida, Takuya Nishinakagawa, Ryoko Yada, Motoyuki Kohjima, Masaki Kato, Kazuhiro Kotoh, Naoya Sakamoto, Goshi Shiota, Makoto Nakamuta, Manabu Nakashima, Munechika Enjoji

研究成果: ジャーナルへの寄稿記事

11 引用 (Scopus)

抄録

Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endo-cannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.

元の言語英語
ページ(範囲)619-624
ページ数6
ジャーナルInternational journal of molecular medicine
27
発行部数5
DOI
出版物ステータス出版済み - 5 1 2011

Fingerprint

Cannabinoids
Hepatitis C
Viruses
Lipids
Genes
Viral Core Proteins
Cannabinoid Receptor CB1
Triglycerides
Virus Diseases
Viral Structural Proteins
Cannabinoid Receptors
Chronic Hepatitis C
Hepatocytes
Cultured Cells
Cell Line

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes. / Toyoda, Mako; Kitaoka, Akira; Machida, Kazuyuki; Nishinakagawa, Takuya; Yada, Ryoko; Kohjima, Motoyuki; Kato, Masaki; Kotoh, Kazuhiro; Sakamoto, Naoya; Shiota, Goshi; Nakamuta, Makoto; Nakashima, Manabu; Enjoji, Munechika.

:: International journal of molecular medicine, 巻 27, 番号 5, 01.05.2011, p. 619-624.

研究成果: ジャーナルへの寄稿記事

Toyoda, M, Kitaoka, A, Machida, K, Nishinakagawa, T, Yada, R, Kohjima, M, Kato, M, Kotoh, K, Sakamoto, N, Shiota, G, Nakamuta, M, Nakashima, M & Enjoji, M 2011, 'Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes', International journal of molecular medicine, 巻. 27, 番号 5, pp. 619-624. https://doi.org/10.3892/ijmm.2011.622
Toyoda, Mako ; Kitaoka, Akira ; Machida, Kazuyuki ; Nishinakagawa, Takuya ; Yada, Ryoko ; Kohjima, Motoyuki ; Kato, Masaki ; Kotoh, Kazuhiro ; Sakamoto, Naoya ; Shiota, Goshi ; Nakamuta, Makoto ; Nakashima, Manabu ; Enjoji, Munechika. / Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes. :: International journal of molecular medicine. 2011 ; 巻 27, 番号 5. pp. 619-624.
@article{fe6b013ea4e34dc9bbd13e99b1f099b2,
title = "Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes",
abstract = "Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endo-cannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.",
author = "Mako Toyoda and Akira Kitaoka and Kazuyuki Machida and Takuya Nishinakagawa and Ryoko Yada and Motoyuki Kohjima and Masaki Kato and Kazuhiro Kotoh and Naoya Sakamoto and Goshi Shiota and Makoto Nakamuta and Manabu Nakashima and Munechika Enjoji",
year = "2011",
month = "5",
day = "1",
doi = "10.3892/ijmm.2011.622",
language = "English",
volume = "27",
pages = "619--624",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes

AU - Toyoda, Mako

AU - Kitaoka, Akira

AU - Machida, Kazuyuki

AU - Nishinakagawa, Takuya

AU - Yada, Ryoko

AU - Kohjima, Motoyuki

AU - Kato, Masaki

AU - Kotoh, Kazuhiro

AU - Sakamoto, Naoya

AU - Shiota, Goshi

AU - Nakamuta, Makoto

AU - Nakashima, Manabu

AU - Enjoji, Munechika

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endo-cannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.

AB - Evidence from clinical and laboratory studies has accumulated indicating that the activation of the cannabinoid system is crucial for steatosis, especially in non-alcoholic fatty liver disease. However, the association between hepatitis C C virus (HCV) infection and the cannabinoid system has not been well investigated and it is unclear whether steatosis in chronic hepatitis C develops via activation of the endo-cannabinoid/cannabinoid receptor signaling pathway. In this study, we examined the expression of a cannabinoid receptor (CB1) and the lipid accumulation in the hepatic Huh7 cell line, expressing HCV genes. We utilized Huh7/Rep-Feo-1b cells stably expressing HCV non-structural proteins (NS) 3, NS4, NS5A, and NS5B, as well as Tet-On Core-2 cells, in which the HCV core protein expression is inducible. Significantly higher levels of stored triglycerides were found in Huh7/Rep-Feo-1b cells compared to Huh7 cells. Also, triglyceride accumulation and CB1 receptor expression were down-regulated in Huh7/Rep-Feo-1b cells after HCV reduction by IFNα. Moreover, lipid accumulation appeared to increase after CB1 agonist treatment, while it decreased after CB1 antagonist treatment, although significant differences were not found compared to untreated cells. In Tet-On Core-2 cells, induction of HCV core protein expression did not affect CB1 expression or triglyceride accumulation. The results of this study in cultured cells suggest that HCV infection may activate the cannabinoid system and precede steatosis, but the core protein by itself may not have any effect on the cannabinoid system.

UR - http://www.scopus.com/inward/record.url?scp=79952976755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952976755&partnerID=8YFLogxK

U2 - 10.3892/ijmm.2011.622

DO - 10.3892/ijmm.2011.622

M3 - Article

VL - 27

SP - 619

EP - 624

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 5

ER -