Involvement of the JAK-STAT Pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage raw 264 cells

Sumio Akifusa, Noriaki Kamio, Yoshihiro Shimazaki, Noboru Yamaguchi, Kazuaki Nonaka, Yoshihisa Yamashita

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.

Original languageEnglish
Pages (from-to)597-606
Number of pages10
JournalJournal of Cellular Biochemistry
Volume111
Issue number3
DOIs
Publication statusPublished - Oct 15 2010

Fingerprint

Janus Kinases
Macrophages
Adiponectin
Transcription
Transducers
Reactive Oxygen Species
Phosphotransferases
Cytokines
Nitric Oxide
Cell death
Phosphorylation
Cell Death
Caspases
STAT3 Transcription Factor
Immunosuppressive Agents
Adipocytes
Small Interfering RNA
Proteins
Western Blotting
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Involvement of the JAK-STAT Pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage raw 264 cells. / Akifusa, Sumio; Kamio, Noriaki; Shimazaki, Yoshihiro; Yamaguchi, Noboru; Nonaka, Kazuaki; Yamashita, Yoshihisa.

In: Journal of Cellular Biochemistry, Vol. 111, No. 3, 15.10.2010, p. 597-606.

Research output: Contribution to journalArticle

Akifusa, Sumio ; Kamio, Noriaki ; Shimazaki, Yoshihiro ; Yamaguchi, Noboru ; Nonaka, Kazuaki ; Yamashita, Yoshihisa. / Involvement of the JAK-STAT Pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage raw 264 cells. In: Journal of Cellular Biochemistry. 2010 ; Vol. 111, No. 3. pp. 597-606.
@article{287237c870604b7cbda8c05d8ae5699c,
title = "Involvement of the JAK-STAT Pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage raw 264 cells",
abstract = "Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.",
author = "Sumio Akifusa and Noriaki Kamio and Yoshihiro Shimazaki and Noboru Yamaguchi and Kazuaki Nonaka and Yoshihisa Yamashita",
year = "2010",
month = "10",
day = "15",
doi = "10.1002/jcb.22745",
language = "English",
volume = "111",
pages = "597--606",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Involvement of the JAK-STAT Pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage raw 264 cells

AU - Akifusa, Sumio

AU - Kamio, Noriaki

AU - Shimazaki, Yoshihiro

AU - Yamaguchi, Noboru

AU - Nonaka, Kazuaki

AU - Yamashita, Yoshihisa

PY - 2010/10/15

Y1 - 2010/10/15

N2 - Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.

AB - Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death.

UR - http://www.scopus.com/inward/record.url?scp=78651283555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651283555&partnerID=8YFLogxK

U2 - 10.1002/jcb.22745

DO - 10.1002/jcb.22745

M3 - Article

C2 - 20564237

AN - SCOPUS:78651283555

VL - 111

SP - 597

EP - 606

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 3

ER -