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Volume 134, Issue 7, Pages (June 2008)

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Presentation on theme: "Volume 134, Issue 7, Pages (June 2008)"— Presentation transcript:

1 Volume 134, Issue 7, Pages 2122-2131 (June 2008)
The Hepatic Vagus Nerve Attenuates Fas-Induced Apoptosis in the Mouse Liver via α7 Nicotinic Acetylcholine Receptor  Tetsuya Hiramoto, Yoichi Chida, Junko Sonoda, Kazufumi Yoshihara, Nobuyuki Sudo, Chiharu Kubo  Gastroenterology  Volume 134, Issue 7, Pages (June 2008) DOI: /j.gastro Copyright © 2008 AGA Institute Terms and Conditions

2 Figure 1 Effect of hepatic vagotomy on urine densities during fasting. (A) Urine densities were measured at 0, 12, 18, and 24 hours after the beginning of fasting in the sham-operated (Sham) or vagotomized (Vago) animals (n = 6 per group). (B) Stomach mass index (stomach weight/body weight) was measured 12 hours after the beginning of fasting in the Sham or Vago animals (n = 8 per group). *P < .05 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

3 Figure 2 Survival curves of the sham-operated and vagotomized mice after Jo-2 injection. (A) Sham-operated (Sham, n =10) and vagotomized (Vago, n =10) mice were monitored following a high dose (0.35 mg/kg weight) of Jo-2. The groups that were not treated with Jo-2 indicate the groups exposed to the control conditions (Jo-2 (−), n = 6 per group). (B) Survival course of mice (n = 10 per group) following a low dose (0.25 mg/kg weight) of Jo-2. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

4 Figure 3 H&E staining, TUNEL assay, and caspase-3 activities of the sham-operated and vagotomized livers after Jo-2 injection. (A) H&E staining of the sham-operated (Sham) or vagotomized (Vago) livers at 3 hours after Jo-2 (0.25-mg/kg weight) injection. Original magnification, 100×. (B) Photomicrographs of TUNEL-positive brown nuclei within hepatocytes. Original magnification, 100×; insets, 400×. (C) Number of TUNEL-positive nuclei per high-power field in the Sham or Vago livers. All values are the mean of 7 fields/group. (D) Caspase-3 activities in the Sham or Vago livers. Sham or Vago livers were collected 1.5 hours and 3 hours after the injection of Jo-2 (n = 8 per group). *P < .05 and **P < .01 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

5 Figure 4 Effect of nicotine supplementation on mortality and liver caspase-3 activities after Jo-2 treatment. (A and D) Survival course of the sham-operated or vagotomized mice pretreated with or without a high dose of nicotine (4-pg/kg weight) or PNU (40-μg/kg weight) 30 minutes before Jo-2-injection (0.25-mg/kg weight, n = 10 per group). The groups that were not treated with Jo-2 indicate the groups exposed to the control conditions (Jo-2 (−), n = 6 per group). (B and E) Survival course of the sham-operated or vagotomized mice pretreated with low dose of nicotine (0.4-pg/kg weight) or PNU (4-μg/kg weight) 30 minutes before Jo-2-injection (0.25-mg/kg weight, n = 10 per group). (C and F) Effect of a high dose of nicotine (4-pg/kg weight) or PNU (40-μg/kg weight) on caspase-3 activities. Sham or Vago livers were collected 3 hours after the injection of Jo-2 (n = 8 per group). *P < .05, **P < .01, and ***P < .001 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

6 Figure 5 Effect of nicotine on the Fas-induced increase in caspase-3 activities in primary hepatocytes culture. (A) Caspase-3 activities after 6-hour incubation with various doses of Jo-2. (B) Caspase-3 activities after 6-hour incubation with various doses of nicotine and μg/mL Jo-2. (C) Caspase-3 activities after 6-hour incubation with various doses of PNU and μg/mL Jo-2. All values are expressed as the mean of 5 samples per group. The results shown are representative of 3 independent experiments. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

7 Figure 6 Kupffer cell elimination suppressed a vagotomy-triggered exacerbation of mortality and caspase-3 activities after Jo-2 treatment. (A) Immunohistochemical staining of liver sections with the anti-mouse F4/80 antibody at 2 days after intravenous treatment with vehicle or lipo-Cl2MDP. Original magnification, 100×. (B) Survival course of the sham-operated (Sham) or vagotomized (Vago) mice pretreated with or without a 50 μL/mouse dose of lipo-Cl2MDP 2 days before Jo-2 injection (0.25-mg/kg weight, n = 10 per group). The groups that were not treated with Jo-2 indicate the groups exposed to the control condition (Jo-2 (−), n = 6 per group). (C) Sham or Vago livers were collected 3 hours after the injection of Jo-2 (n = 8 per group). *P < .05 and **P < .01 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

8 Figure 7 MDA levels in the sham-operated and vagotomized livers and the effect of MnTBAP treatment on mortality and liver caspase-3 activities after Jo-2 treatment. (A) Liver MDA levels were measured in the sham-operated (Sham) or vagotomized (Vago) livers at 1.5 and 3 hours after the injection of Jo-2 (0.25-mg/kg weight). All values are the mean of 8 mice per group. (B) Survival course of the Sham or Vago mice pretreated with or without a 5-mg/kg weight dose of MnTBAP 1 hour before the Jo-2 injection (0.25-mg/kg weight, n = 10 per group). The groups that were not treated with Jo-2 indicate the groups exposed to the control conditions (Jo-2 (−), n = 6 per group). (C) Sham or Vago livers were collected 3 hours after the injection of Jo-2 (n = 8 per group). *P < .05 and **P < .01 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions

9 Figure 8 Hepatic vagotomy accelerated a Fas-induced increase in caspase-8 and caspase-9 activities in the liver. (A and B) Caspase-8 and caspase-9 activities were measured in the sham-operated (Sham) or vagotomized (Vago) livers 1.5 and 3 hours after the injection of Jo-2 (n = 8 per group). *P < .05 and **P < .01 in comparison with the corresponding value. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2008 AGA Institute Terms and Conditions


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