Intestinal and hepatic expression of BNIP3 in necrotizing enterocolitis: Regulation by nitric oxide and peroxynitrite

Ruben Zamora, Yoram Vodovotz, Binnie Betten, Catalina Wong, Brian Zuckerbraun, Kevin F. Gibson, Henri Ford

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Necrotizing enterocolitis (NEC) is characterized by the upregulation of proinflammatory proteins, nitrosative stress, and increased enterocyte apoptosis. We examined the expression and regulation of the Bcl-2/adenovirus EIB 19-kDa-interacting protein 3 (BNIP3), a pro-apoptotic gene regulated by nitric oxide (NO) in hepatocytes, in NEC. Newborn rats subjected to hypoxia and fed a conventional formula by gavage (FFH) developed NEC and demonstrated elevated expression of BNIP3 mRNA and protein in mucosal scrapings of the ileal samples and in the liver. In contrast, control rats [breast-fed (BF) without hypoxia] did not develop NEC or elevated BNIP3 expression in these tissues. BNIP3 expression paralleled the histological manifestation of NEC. Supplementation of the formula with L-Nω-(1-minoethyl)lysine, an inducible NO synthase inhibitor, reduced BNIP3 expression in FFH animals to the levels found in BF animals. Both hypoxia and peroxynitrite upregulated BNIP3 protein expression in human intestinal cells. Finally, ileal samples obtained from infants undergoing surgical resection for acute NEC demonstrated higher levels of BNIP3 protein. Because hypoxia and formation of reactive nitrogen species may promote gut barrier failure, we propose that upregulation of the cell death-related protein BNIP3 is one possible mechanism associated with enterocyte cell death observed in the intestine with NEC.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume289
Issue number5 52-5
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Fingerprint

Necrotizing Enterocolitis
Peroxynitrous Acid
Nitric Oxide
Liver
Enterocytes
Proteins
Breast
Cell Death
Up-Regulation
Reactive Nitrogen Species
Nitric Oxide Synthase Type II
Heat-Shock Proteins
Adenoviridae
Lysine
Intestines
Hepatocytes
Apoptosis
Messenger RNA
Hypoxia
Genes

Keywords

  • Apoptosis
  • Bcl-2/adenovirus EIB 19-kDa-interacting protein 3
  • Gene regulation
  • Inflammation
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Intestinal and hepatic expression of BNIP3 in necrotizing enterocolitis : Regulation by nitric oxide and peroxynitrite. / Zamora, Ruben; Vodovotz, Yoram; Betten, Binnie; Wong, Catalina; Zuckerbraun, Brian; Gibson, Kevin F.; Ford, Henri.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 289, No. 5 52-5, 01.11.2005.

Research output: Contribution to journalArticle

Zamora, Ruben ; Vodovotz, Yoram ; Betten, Binnie ; Wong, Catalina ; Zuckerbraun, Brian ; Gibson, Kevin F. ; Ford, Henri. / Intestinal and hepatic expression of BNIP3 in necrotizing enterocolitis : Regulation by nitric oxide and peroxynitrite. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 289, No. 5 52-5.
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