AIM： Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increa...AIM： Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide （NO） and carbon monoxide （CO） through the expression of nitric oxide synthase （NOS） and heme oxygenase （HO）. METHOD： Cirrhotic （n = 20） and non-cirrhotic （n = 20） livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry. RESULTS： There was no significant change in either inducible NOS （iNOS） or neuronal NOS （nNOS） expressions while endothelial NOS （eNOS） was up- regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was upregulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different Iocalizations. CONCLUSION： The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.展开更多
Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but d...Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a non-heme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.展开更多
AIM： To determine if the fraction of Nardostachysjata- mansi （N J） has the potential to ameliorate the severity of acute pancreatitis （AP）. METHODS： Mice were administered the biologically active fraction of N J...AIM： To determine if the fraction of Nardostachysjata- mansi （N J） has the potential to ameliorate the severity of acute pancreatitis （AP）. METHODS： Mice were administered the biologically active fraction of N J, i.e., the 4th fraction （N J4）, intra- peritoneally, and then injected with the stable chole- cystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination,measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS： N J4 administration attenuated the sever- ity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heine oxy- genase-1 （HO-1）. Furthermore, NJ4 and its biologically active fraction, N J4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pan- creatic acinar cells. CONCLUSION： These results suggest that N J4 may be a candidate fraction offering protection in AP and N J4 might ameliorate the severity of pancreatitis by induc- ing HO-1 expression.展开更多
The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to establish a cell model of Alzheimer＇s disease. Graded concentration and time course experiments demonstrate that curcumin significantly u...The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to establish a cell model of Alzheimer＇s disease. Graded concentration and time course experiments demonstrate that curcumin significantly upregulates phosphatidylinositol 3-kinase （PI3K）, Akt, nuclear factor E2-related factor-2 （Nrf2）, heme oxygenase 1 and ferritin expression, and that it significantly downregulates heme oxygenase 2, reactive oxygen species and amyloid-beta 40/42 expression. These effects of curcumin on PI3K, Akt and Nrf2 were blocked by LY294002 （PI3k inhibitor） and NF-E2-related factor-2 siRNA. The results indicate that the cytoprotection conferred by curcumin on APPswe transfected SH-SY5Y cells is mediated by its ability to regulate the balance between heme oxygenase 1 and 2 via the PI3K/Akt/Nrf2 intracellular signaling pathway.展开更多
基金Supported by Research Biolabs Pte Ltd.Beatrice J Goh is a recipient of the Research Scholarship awarded by the National University of Singapore
文摘AIM： Portal hypertension is a common complication of liver cirrhosis. Intrahepatic pressure can be elevated in several ways. Abnormal architecture affecting the vasculature, an increase in vasoconstrictors and increased circulation from the splanchnic viscera into the portal system may all contribute. It follows that endogenous vasodilators may be able to alleviate the hypertension. We therefore aimed to investigate the levels of endogenous vasodilators, nitric oxide （NO） and carbon monoxide （CO） through the expression of nitric oxide synthase （NOS） and heme oxygenase （HO）. METHOD： Cirrhotic （n = 20） and non-cirrhotic （n = 20） livers were obtained from patients who had undergone surgery. The mRNA and protein expressions of the various isoforms of NOS and HO were examined using competitive PCR, Western Blot and immunohistochemistry. RESULTS： There was no significant change in either inducible NOS （iNOS） or neuronal NOS （nNOS） expressions while endothelial NOS （eNOS） was up- regulated in cirrhotic livers. Concomitantly, caveolin-1, an established down-regulator of eNOS, was upregulated. Inducible HO-1 and constitutive HO-2 were found to show increased expression in cirrhotic livers albeit in different Iocalizations. CONCLUSION： The differences of NOS expression might be due to their differing roles in maintaining liver homeostasis and/or involvement in the pathology of cirrhosis. Sheer stress within the hypertensive liver may induce increased expression of eNOS. In turn, caveolin-1 is also increased. Whether this serves as a defense mechanism against further cirrhosis or is a consequence of cirrhosis, is yet unknown. The elevated expression of HO-1 and HO-2 suggest that CO may compensate in its role as a vasodilator albeit weakly. It is possible that CO and NO have parallel or coordinated functions within the liver and may work antagonistically in the pathophysiology of portal hypertension.
文摘Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a non-heme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.
基金Supported by The Ministry of Education,Science and Technology at Wonkwang University,No. MEST 2010-0017094
文摘AIM： To determine if the fraction of Nardostachysjata- mansi （N J） has the potential to ameliorate the severity of acute pancreatitis （AP）. METHODS： Mice were administered the biologically active fraction of N J, i.e., the 4th fraction （N J4）, intra- peritoneally, and then injected with the stable chole- cystokinin analogue cerulein hourly for 6 h. Six hours after the last cerulein injection, the pancreas, lung, and blood were harvested for morphological examination,measurement of cytokine expression, and examination of neutrophil infiltration. RESULTS： N J4 administration attenuated the sever- ity of AP and lung injury associated with AP. It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heine oxy- genase-1 （HO-1）. Furthermore, NJ4 and its biologically active fraction, N J4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pan- creatic acinar cells. CONCLUSION： These results suggest that N J4 may be a candidate fraction offering protection in AP and N J4 might ameliorate the severity of pancreatitis by induc- ing HO-1 expression.
基金supported by the National Science Foundation of China,No.30973154the Science Foundation of Chongqing,No.2009BB5270the Chongqing Municipal Education Commission Foundation,No.KJ090301
文摘The APPswe plasmid was transfected into the neuroblastoma cell line SH-SY5Y to establish a cell model of Alzheimer＇s disease. Graded concentration and time course experiments demonstrate that curcumin significantly upregulates phosphatidylinositol 3-kinase （PI3K）, Akt, nuclear factor E2-related factor-2 （Nrf2）, heme oxygenase 1 and ferritin expression, and that it significantly downregulates heme oxygenase 2, reactive oxygen species and amyloid-beta 40/42 expression. These effects of curcumin on PI3K, Akt and Nrf2 were blocked by LY294002 （PI3k inhibitor） and NF-E2-related factor-2 siRNA. The results indicate that the cytoprotection conferred by curcumin on APPswe transfected SH-SY5Y cells is mediated by its ability to regulate the balance between heme oxygenase 1 and 2 via the PI3K/Akt/Nrf2 intracellular signaling pathway.
