Carbon Monoxide Releasing Molecule-2 Inhibits Pancreatic Stellate Cell Proliferation by Activating p38 Mitogen-Activated Protein Kinase/Heme Oxygenase-1 Signaling

2010 ◽  
Vol 77 (4) ◽  
pp. 660-669 ◽  
Author(s):  
Christian I. Schwer ◽  
Manuel Mutschler ◽  
Patrick Stoll ◽  
Ulrich Goebel ◽  
Matjaz Humar ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Carbon Monoxide ◽  
Protein Kinase ◽  
Heme Oxygenase ◽  
Stellate Cell ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Pancreatic Stellate Cell ◽  
Mitogen Activated Protein

Amelioration of estrogen-induced endometrial hyperplasia in female rats by hemin via heme-oxygenase-1 expression, suppression of iNOS, p38 MAPK, and Ki67

2019 ◽  
Vol 97 (12) ◽  
pp. 1159-1168
Author(s):  
Fatma F. Ali ◽  
Walaa Yehia Abdelzaher ◽  
Randa Ahmed Ibrahim ◽  
Doaa Mohamed Elroby Ali
Keyword(s):  
Protein Kinase ◽  
Heme Oxygenase ◽  
Endometrial Hyperplasia ◽  
Mitogen Activated Protein Kinase ◽  
Female Rats ◽  
Interleukin 1Β ◽  
Estradiol Valerate ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Mitogen Activated Protein

Although heme oxygenase-1 (HO-1) is part of an endogenous defense system implicated in the homeostatic response, its role in cell proliferation and tumor progression is still controversial. Endometrial hyperplasia (EH) is associated with high risk of endometrial cancer (EC). Therefore, we aimed to evaluate the effect of hemin, a HO-1 inducer, against EH. Thirty-two female rats (60–70 days old) were divided into 4 groups treated for 1 week: vehicle control group, hemin group (25 mg/kg; i.p. 3 times/week), estradiol valerate (EV) group (2 mg/kg per day, p.o.), and hemin plus EV group. Sera were obtained for reduced glutathione level. Uterine malondialdehyde, superoxide dismutase, total nitrite/nitrate, and interleukin-1β levels were estimated. HO-1 and p38 mitogen-activated protein kinase expressions were obtained in uterine tissue. Uterine histological and immunohistochemical assessment of iNOS and Ki67 were also done. Results demonstrated that upregulation of HO-1 expression in hemin plus EV rats led to amelioration of EH which was confirmed with histological examination. This was associated with significant decrease in oxidative stress parameters, p38 mitogen-activated protein kinase expression, and interleukin-1β level. Also, uterine iNOS and Ki67 expressions were markedly suppressed. In conclusion, upregulation of HO-1 expression via hemin has ameliorative effect against EH through its antioxidant, anti-inflammatory, and antiproliferative actions.

scholarly journals Amitriptyline Suppresses Neuroinflammation-dependent Interleukin-10-p38 Mitogen-activated Protein Kinase-Heme Oxygenase-1 Signaling Pathway in Chronic Morphine-infused Rats

2009 ◽  
Vol 110 (6) ◽  
pp. 1379-1389 ◽  
Author(s):  
Yueh-Hua Tai ◽  
Ru-Yin Tsai ◽  
Shinn-Long Lin ◽  
Chun-Chang Yeh ◽  
Jhi-Joung Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Heme Oxygenase ◽  
Antinociceptive Effect ◽  
Interleukin 10 ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Antiinflammatory Effect ◽  
Chronic Morphine ◽  
Mitogen Activated Protein

Background This study explores the underlying mechanism of the antiinflammatory effect of amitriptyline in chronic morphine-infused rats. Methods Male Wistar rats were implanted with two intrathecal catheters. One catheter was for the continuous infusion of saline, amitriptyline (15 microg/h), morphine (15 microg/h), p38 mitogen-activated protein kinase inhibitor SB203580 (0.5 microg/h), morphine plus amitriptyline, or morphine plus amitriptyline plus SB203580 for 5 days. The other catheter was used for daily intrathecal injection of anti-interleukin-10 (IL-10) antibody or heme oxygenase-1 inhibitor zinc protoporphyrin for 5 days. Results Amitriptyline/morphine coinfusion upregulated IL-10 protein expression in microglia; this was not observed in morphine-infused rats. Anti-IL-10 antibody effectively neutralized the amitriptyline-induced IL-10 expression in chronic morphine-infused rats. In addition, coinfusion of amitriptyline restored the antinociceptive effect of morphine (a 4.8-fold right-shift of the morphine dose-response curve compared to a 77.8-fold right-shift in its absence), and the injection of anti-IL-10 antibody or coinfusion of SB203580 partially reversed the effect of amitriptyline on the antinociceptive effect of morphine in morphine-infused rats (a 17.9-fold and 15.1-fold right-shift in morphine dose-response curves). Anti-IL-10 antibody and SB203580 significantly inhibited the amitriptyline-induced p38 mitogen-activated protein kinase and heme oxygenase-1 expression and the associated antiinflammatory effect of amitriptyline. Daily injection of zinc protoporphyrin also demonstrated that it reverses the effect of amitriptyline in morphine's antinociception and antiinflammation in chronic morphine-infused rats. Conclusions These results suggest that the antiinflammatory effect of amitriptyline on morphine tolerance, probably acting by increasing IL-10 expression, is mediated by p38 mitogen-activated protein kinase heme oxygenase-1 signal transduction cascade.

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