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Characterization of the expression of inducible nitric oxide synthase in rat and human liver during hemorrhagic shock
- Source :
- Shock (Augusta, Ga.). 19(2)
- Publication Year :
- 2003
-
Abstract
- It has been previously shown that the inducible nitric oxide (NO) synthase (iNOS; NOS-2) is elevated after hemorrhage, and that iNOS-derived NO participates in the upregulation of inflammation as well as lung and liver injury postresuscitation from shock. The purpose of this study was to elucidate the time course of iNOS mRNA expression, as well as the cellular and subcellular localization of iNOS protein in the liver posthemorrhage in rats subjected to varying durations of hemorrhagic shock (HS; mean arterial blood pressure [MAP] = 40 mmHg) with or without resuscitation. Expression of iNOS mRNA in rat liver by real-time reverse transcriptase (RT)-PCR demonstrated iNOS upregulation in shocked animals as compared with their sham counterparts as early as 60 min after the initiation of hemorrhage. By 1 h of HS, iNOS protein was detectable in rat liver by immunofluorescence, and this expression increased with time. Immunofluorescence localized iNOS primarily to the hepatocytes, and in particular to hepatocytes in the centrilobular regions. This analysis, confirmed by immunoelectron microscopy, revealed that iNOS colocalizes with catalase, a peroxisomal marker. Furthermore, we determined that iNOS mRNA is detectable by RT-PCR in liver biopsies from human subjects with HS (MAP90 mmHg) associated with trauma (n = 18). In contrast, none of the seven nontrauma surgical patients studied had detectable iNOS mRNA in their livers. Collectively, these results suggest that hepatic iNOS expression, associated with peroxisomal localization, is an early molecular response to HS in experimental animals and possibly in human patients with trauma with HS.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Time Factors
Biopsy
Nitric Oxide Synthase Type II
Inflammation
Biology
Shock, Hemorrhagic
Critical Care and Intensive Care Medicine
Nitric oxide
Rats, Sprague-Dawley
chemistry.chemical_compound
Cytosol
Downregulation and upregulation
Gene expression
medicine
Peroxisomes
Animals
Humans
RNA, Messenger
Microscopy, Immunoelectron
Liver injury
Microscopy, Confocal
ATP synthase
Reverse Transcriptase Polymerase Chain Reaction
medicine.disease
Catalase
Molecular biology
Rats
Up-Regulation
Nitric oxide synthase
chemistry
Liver
Shock (circulatory)
Emergency Medicine
biology.protein
Hepatocytes
medicine.symptom
Nitric Oxide Synthase
Subjects
Details
- ISSN :
- 10732322
- Volume :
- 19
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Shock (Augusta, Ga.)
- Accession number :
- edsair.doi.dedup.....6a9cbbfaeb7acba821051c909b724112