Intestinal mitochondrial apoptotic signaling is activated during oxidative stress

Naira Baregamian; Jun Song; John Papaconstantinou; Hal K. Hawkins; B. Mark Evers; Dai H. Chung

doi:10.1007/s00383-011-2880-x

Intestinal mitochondrial apoptotic signaling is activated during oxidative stress

Naira Baregamian, Jun Song, John Papaconstantinou, Hal K. Hawkins, B. Mark Evers, Dai H. Chung

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Purpose: Reactive oxygen species (ROS) are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC). Mitochondria as a major source of intracellular ROS and apoptotic signaling during oxidative stress in NEC have not been investigated. We sought to determine: (1) the effects of oxidative stress on intestinal mitochondrial apoptotic signaling, and (2) the role of growth factors in this process. Methods: We used Swiss-Webster mice pups, and rat intestinal epithelial (RIE)-1, mitochondrial DNA-depleted RIE-1 cell line (RIE-1-ρ°) and human fetal intestinal epithelial cells (FHs74 Int) for our studies. Results: H ₂O ₂ induced apoptosis and ROS production. ROS-mediated activation of apoptotic signaling was significantly attenuated with mitochondrial silencing in RIE-1-ρ° cells. Growth factors, especially IGF-1, attenuated this response to H ₂O ₂ in intestinal epithelial cells. Conclusions: Our findings suggest that mitochondria are a major source of intestinal apoptotic signaling during oxidative stress, and modulating mitochondrial apoptotic responses may help ameliorate the effects of NEC.

Original language	English
Pages (from-to)	871-877
Number of pages	7
Journal	Pediatric Surgery International
Volume	27
Issue number	8
DOIs	https://doi.org/10.1007/s00383-011-2880-x
State	Published - Aug 2011

Bibliographical note

Funding Information:
The authors thank Karen Martin for manuscript preparation. This work was supported by grants R01 DK61470, R01 DK48498, P01 DK35608 and T32 DK07639 from the National Institutes of Health and a grant 8580 from Shriners Hospital for Children.

Funding

The authors thank Karen Martin for manuscript preparation. This work was supported by grants R01 DK61470, R01 DK48498, P01 DK35608 and T32 DK07639 from the National Institutes of Health and a grant 8580 from Shriners Hospital for Children.

Funders	Funder number
National Institutes of Health (NIH)	8580
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK061470, R01DK048498, T32DK007639, P01DK035608
Shriners Hospitals for Children Cincinnati

Keywords

Growth factors
Intestinal epithelial cells
Mitochondrial apoptotic signaling
Necrotizing enterocolitis
Oxidative stress
Reactive oxygen species

ASJC Scopus subject areas

Surgery
Pediatrics, Perinatology, and Child Health

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10.1007/s00383-011-2880-x

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title = "Intestinal mitochondrial apoptotic signaling is activated during oxidative stress",

abstract = "Purpose: Reactive oxygen species (ROS) are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC). Mitochondria as a major source of intracellular ROS and apoptotic signaling during oxidative stress in NEC have not been investigated. We sought to determine: (1) the effects of oxidative stress on intestinal mitochondrial apoptotic signaling, and (2) the role of growth factors in this process. Methods: We used Swiss-Webster mice pups, and rat intestinal epithelial (RIE)-1, mitochondrial DNA-depleted RIE-1 cell line (RIE-1-ρ°) and human fetal intestinal epithelial cells (FHs74 Int) for our studies. Results: H 2O 2 induced apoptosis and ROS production. ROS-mediated activation of apoptotic signaling was significantly attenuated with mitochondrial silencing in RIE-1-ρ° cells. Growth factors, especially IGF-1, attenuated this response to H 2O 2 in intestinal epithelial cells. Conclusions: Our findings suggest that mitochondria are a major source of intestinal apoptotic signaling during oxidative stress, and modulating mitochondrial apoptotic responses may help ameliorate the effects of NEC.",

keywords = "Growth factors, Intestinal epithelial cells, Mitochondrial apoptotic signaling, Necrotizing enterocolitis, Oxidative stress, Reactive oxygen species",

author = "Naira Baregamian and Jun Song and John Papaconstantinou and Hawkins, \{Hal K.\} and Evers, \{B. Mark\} and Chung, \{Dai H.\}",

note = "Funding Information: The authors thank Karen Martin for manuscript preparation. This work was supported by grants R01 DK61470, R01 DK48498, P01 DK35608 and T32 DK07639 from the National Institutes of Health and a grant 8580 from Shriners Hospital for Children.",

year = "2011",

month = aug,

doi = "10.1007/s00383-011-2880-x",

language = "English",

volume = "27",

pages = "871--877",

number = "8",

}

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T1 - Intestinal mitochondrial apoptotic signaling is activated during oxidative stress

AU - Baregamian, Naira

AU - Song, Jun

AU - Papaconstantinou, John

AU - Hawkins, Hal K.

AU - Evers, B. Mark

AU - Chung, Dai H.

N1 - Funding Information: The authors thank Karen Martin for manuscript preparation. This work was supported by grants R01 DK61470, R01 DK48498, P01 DK35608 and T32 DK07639 from the National Institutes of Health and a grant 8580 from Shriners Hospital for Children.

PY - 2011/8

Y1 - 2011/8

N2 - Purpose: Reactive oxygen species (ROS) are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC). Mitochondria as a major source of intracellular ROS and apoptotic signaling during oxidative stress in NEC have not been investigated. We sought to determine: (1) the effects of oxidative stress on intestinal mitochondrial apoptotic signaling, and (2) the role of growth factors in this process. Methods: We used Swiss-Webster mice pups, and rat intestinal epithelial (RIE)-1, mitochondrial DNA-depleted RIE-1 cell line (RIE-1-ρ°) and human fetal intestinal epithelial cells (FHs74 Int) for our studies. Results: H 2O 2 induced apoptosis and ROS production. ROS-mediated activation of apoptotic signaling was significantly attenuated with mitochondrial silencing in RIE-1-ρ° cells. Growth factors, especially IGF-1, attenuated this response to H 2O 2 in intestinal epithelial cells. Conclusions: Our findings suggest that mitochondria are a major source of intestinal apoptotic signaling during oxidative stress, and modulating mitochondrial apoptotic responses may help ameliorate the effects of NEC.

AB - Purpose: Reactive oxygen species (ROS) are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC). Mitochondria as a major source of intracellular ROS and apoptotic signaling during oxidative stress in NEC have not been investigated. We sought to determine: (1) the effects of oxidative stress on intestinal mitochondrial apoptotic signaling, and (2) the role of growth factors in this process. Methods: We used Swiss-Webster mice pups, and rat intestinal epithelial (RIE)-1, mitochondrial DNA-depleted RIE-1 cell line (RIE-1-ρ°) and human fetal intestinal epithelial cells (FHs74 Int) for our studies. Results: H 2O 2 induced apoptosis and ROS production. ROS-mediated activation of apoptotic signaling was significantly attenuated with mitochondrial silencing in RIE-1-ρ° cells. Growth factors, especially IGF-1, attenuated this response to H 2O 2 in intestinal epithelial cells. Conclusions: Our findings suggest that mitochondria are a major source of intestinal apoptotic signaling during oxidative stress, and modulating mitochondrial apoptotic responses may help ameliorate the effects of NEC.

KW - Growth factors

KW - Intestinal epithelial cells

KW - Mitochondrial apoptotic signaling

KW - Necrotizing enterocolitis

KW - Oxidative stress

KW - Reactive oxygen species

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JO - Pediatric Surgery International

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Intestinal mitochondrial apoptotic signaling is activated during oxidative stress

Abstract

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Keywords

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