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Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity.

Kim HS, Jung YY, Do SI - Braz. J. Med. Biol. Res. (2014)

Bottom Line: At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules.The majority of positively stained cells showed a strong intensity of iNOS expression.These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

ABSTRACT
Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

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Effect of hypergravity exposure on inducible nitric oxide synthase (iNOS)protein expression in the livers of mice. A, The control groupshowed no cytoplasmic iNOS immunoreactivity in the hepatocytes, except for ademarcation of sinusoidal endothelial cells by iNOS. B, The 0h group showed weak iNOS immunoreactivity in the cytoplasm of some hepatocytes(arrowheads) surrounding the terminal hepatic venules. C, Inthe 1 h group, the intensity and proportion of iNOS expression in thehepatocytes (arrowheads) were nearly identical to those of the 0 h group.D, The 3 h group revealed a significantly increasedstaining intensity of iNOS expression in the perivenular hepatocytes (arrows),compared with that of the 0 or 1 h groups. E, The 6 h groupdisplayed an increased number of iNOS-positive hepatocytes, with a moderate tostrong intensity of expression (double arrowheads). F, In the12 h group, maximal expression of iNOS protein was observed and the number ofiNOS-positive hepatocytes was increased. The majority of those cells exhibiteda strong intensity (double arrowheads). G, The 18 h groupshowed no iNOS immunoreactivity in the hepatocytes. Polymer method. Originalmagnification, 150×.
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f02: Effect of hypergravity exposure on inducible nitric oxide synthase (iNOS)protein expression in the livers of mice. A, The control groupshowed no cytoplasmic iNOS immunoreactivity in the hepatocytes, except for ademarcation of sinusoidal endothelial cells by iNOS. B, The 0h group showed weak iNOS immunoreactivity in the cytoplasm of some hepatocytes(arrowheads) surrounding the terminal hepatic venules. C, Inthe 1 h group, the intensity and proportion of iNOS expression in thehepatocytes (arrowheads) were nearly identical to those of the 0 h group.D, The 3 h group revealed a significantly increasedstaining intensity of iNOS expression in the perivenular hepatocytes (arrows),compared with that of the 0 or 1 h groups. E, The 6 h groupdisplayed an increased number of iNOS-positive hepatocytes, with a moderate tostrong intensity of expression (double arrowheads). F, In the12 h group, maximal expression of iNOS protein was observed and the number ofiNOS-positive hepatocytes was increased. The majority of those cells exhibiteda strong intensity (double arrowheads). G, The 18 h groupshowed no iNOS immunoreactivity in the hepatocytes. Polymer method. Originalmagnification, 150×.

Mentions: Immunohistochemical staining for iNOS was performed to determine the qualitativedistribution of iNOS protein expression in the liver tissue of the mice exposed tohypergravity. The pattern of iNOS protein expression paralleled that of iNOS mRNAexpression. Even though there was a sharp demarcation of the hepatic sinusoidalendothelial cells by iNOS (Figure 2A), thecontrol group showed no cytoplasmic iNOS expression in the hepatocytes. The mice thathad been exposed to +3 Gz showed iNOS immunoreactivity in the hepatocyte cytoplasm,although the intensity and proportion of the reactions were uneven. Weak cytoplasmiciNOS immunoreactivity was observed in some hepatocytes surrounding terminal hepaticvenules in the 0 (Figure 2B) and 1 h (Figure 2C) groups. In the 3 h group, the number ofiNOS-positive perivenular hepatocytes was greater and the intensity of expression wasstronger than in the 0 h group (Figure 2D). The6 h group revealed a higher proportion and stronger intensity of iNOS expression thanthe 3 h group (Figure 2E). In the 12 h group,the number of iNOS-positive hepatocytes increased, and the majority of those cellsexhibited a strong intensity of expression (Figure2F). In a few foci, strong cytoplasmic iNOS immunoreactivity was observedin the midzonal hepatocytes. In contrast, at 18 (Figure 2G) and 24 h, no iNOS protein expression was observed inhepatocytes. No disorder was observed in the trabecular arrangement of hepatocytes orsinusoidal structure of the livers of either the control or the centrifugedgroup.


Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity.

Kim HS, Jung YY, Do SI - Braz. J. Med. Biol. Res. (2014)

Effect of hypergravity exposure on inducible nitric oxide synthase (iNOS)protein expression in the livers of mice. A, The control groupshowed no cytoplasmic iNOS immunoreactivity in the hepatocytes, except for ademarcation of sinusoidal endothelial cells by iNOS. B, The 0h group showed weak iNOS immunoreactivity in the cytoplasm of some hepatocytes(arrowheads) surrounding the terminal hepatic venules. C, Inthe 1 h group, the intensity and proportion of iNOS expression in thehepatocytes (arrowheads) were nearly identical to those of the 0 h group.D, The 3 h group revealed a significantly increasedstaining intensity of iNOS expression in the perivenular hepatocytes (arrows),compared with that of the 0 or 1 h groups. E, The 6 h groupdisplayed an increased number of iNOS-positive hepatocytes, with a moderate tostrong intensity of expression (double arrowheads). F, In the12 h group, maximal expression of iNOS protein was observed and the number ofiNOS-positive hepatocytes was increased. The majority of those cells exhibiteda strong intensity (double arrowheads). G, The 18 h groupshowed no iNOS immunoreactivity in the hepatocytes. Polymer method. Originalmagnification, 150×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230283&req=5

f02: Effect of hypergravity exposure on inducible nitric oxide synthase (iNOS)protein expression in the livers of mice. A, The control groupshowed no cytoplasmic iNOS immunoreactivity in the hepatocytes, except for ademarcation of sinusoidal endothelial cells by iNOS. B, The 0h group showed weak iNOS immunoreactivity in the cytoplasm of some hepatocytes(arrowheads) surrounding the terminal hepatic venules. C, Inthe 1 h group, the intensity and proportion of iNOS expression in thehepatocytes (arrowheads) were nearly identical to those of the 0 h group.D, The 3 h group revealed a significantly increasedstaining intensity of iNOS expression in the perivenular hepatocytes (arrows),compared with that of the 0 or 1 h groups. E, The 6 h groupdisplayed an increased number of iNOS-positive hepatocytes, with a moderate tostrong intensity of expression (double arrowheads). F, In the12 h group, maximal expression of iNOS protein was observed and the number ofiNOS-positive hepatocytes was increased. The majority of those cells exhibiteda strong intensity (double arrowheads). G, The 18 h groupshowed no iNOS immunoreactivity in the hepatocytes. Polymer method. Originalmagnification, 150×.
Mentions: Immunohistochemical staining for iNOS was performed to determine the qualitativedistribution of iNOS protein expression in the liver tissue of the mice exposed tohypergravity. The pattern of iNOS protein expression paralleled that of iNOS mRNAexpression. Even though there was a sharp demarcation of the hepatic sinusoidalendothelial cells by iNOS (Figure 2A), thecontrol group showed no cytoplasmic iNOS expression in the hepatocytes. The mice thathad been exposed to +3 Gz showed iNOS immunoreactivity in the hepatocyte cytoplasm,although the intensity and proportion of the reactions were uneven. Weak cytoplasmiciNOS immunoreactivity was observed in some hepatocytes surrounding terminal hepaticvenules in the 0 (Figure 2B) and 1 h (Figure 2C) groups. In the 3 h group, the number ofiNOS-positive perivenular hepatocytes was greater and the intensity of expression wasstronger than in the 0 h group (Figure 2D). The6 h group revealed a higher proportion and stronger intensity of iNOS expression thanthe 3 h group (Figure 2E). In the 12 h group,the number of iNOS-positive hepatocytes increased, and the majority of those cellsexhibited a strong intensity of expression (Figure2F). In a few foci, strong cytoplasmic iNOS immunoreactivity was observedin the midzonal hepatocytes. In contrast, at 18 (Figure 2G) and 24 h, no iNOS protein expression was observed inhepatocytes. No disorder was observed in the trabecular arrangement of hepatocytes orsinusoidal structure of the livers of either the control or the centrifugedgroup.

Bottom Line: At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules.The majority of positively stained cells showed a strong intensity of iNOS expression.These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

ABSTRACT
Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Show MeSH
Related in: MedlinePlus