Expression and function of heme oxygenase-1 in human gastric cancer

2012 ◽  
Vol 237 (4) ◽  
pp. 362-371 ◽  
Author(s):  
Yujing Yin ◽  
Qingjun Liu ◽  
Bo Wang ◽  
Gan Chen ◽  
Li Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Heme Oxygenase ◽  
Close Association ◽  
Protoporphyrin Ix ◽  
Clinicopathological Characteristics ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Human Gastric Cancer ◽  
Cobalt Protoporphyrin ◽  
And Function

Heme oxygenase-1 (HO-1) potently influences tumor growth and metastasis. To date, no study has been performed on HO-1 expression pattern and its clinicopathological significance in human gastric cancer (GC) cases. In this study, the expression of HO-1 in human GC tissues ( n = 74) and matched non-tumoral adjacent parenchyma ( n = 46) was investigated by immunohistochemistry. The correlation of HO-1 with the clinicopathological characteristics was analyzed. Results showed that HO-1 was expressed in 62 GC tissues from 74 cases (83.8%), which is significantly higher than non-tumoral adjacent parenchyma (20/46, 43.8%, P < 0.05). A high HO-1 expression rate showed a close association with well/moderate histological differentiation and negative lymph node metastasis ( P < 0.05). The expression of matrix metallopeptidase 9 (MMP9) and vascular endothelial growth factor A (VEGF-A) as well as chemosensitivity to cisplatin of MKN-45 cell lines with genetically altered HO-1 status were then determined by realtime polymerase chain reaction and 3-(4,5 dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. Whether the induction or inhibition of HO-1 by cobalt-protoporphyrin-IX (CoPP) or zinc-protoporphyrin-IX (ZnPP) could affect the sensitivity of MKN-45 cells to cisplatin was also studied. Results showed that the expression of MMP9 and VEGF-A were up-regulated in MKN-45 cells overexpressing HO-1, and down-regulated in HO-1 interfered cells. HO-1 overexpression could lead to an increased resistance to cisplatin, whereas down-regulation of HO-1 expression by siRNA or chemical inhibition of HO-1 could lead to increased chemosensitivity to cisplatin in MKN-45 cells. HO-1 may have multiple effects on protection against carcinogenesis and progression in GC.

scholarly journals Protection from pneumonic plague by the induction of heme oxygenase-1

2018 ◽  
Author(s):  
◽  
Joshua Willix
Keyword(s):  
Heme Oxygenase ◽  
Protoporphyrin Ix ◽  
Lung Damage ◽  
Mammalian Host ◽  
Heme Oxygenase 1 ◽  
Cobalt Protoporphyrin ◽  
Type 3 Secretion System ◽  
Immune Sensing ◽  
Type 3 ◽  
Innate Immune Sensing

Yersinia pestis is the etiological agent of the disease known as plague. The pathology of this disease is characterized by organ failure due to necrosis and hyperinflammation towards the end of the disease. However, Y. pestis has a type 3 secretion system (T3SS) with effector Yops that stifle inflammation, a pgm locus that enables better survival within the mammalian host, and a tetraacylated LPS that renders innate immune sensing by TLR4 anti-stimulatory. Based on the evidence of these virulence factors, added with the lack of inflammation that is present at the beginning of the infection we made the hypothesis that the inflammation may not be related to the pathogen, but to the damage the pathogen creates. This led our laboratory to investigate the damage to the host as the potential source of this hyperinflammation response. We found that the production of yersiniabactin was necessary to induce damage and establish Y. pestis colonies in the lung. This lung damage induced the cytoprotective enzyme heme oxygenase-1, which is an enzyme that catalyzes heme degradation into CO, biliverdin, and Fe2+. We show that by upregulating HO-1 activity by administering a compound, cobalt protoporphyrin IX, we were able to ameliorate the hyperinflammation, lessen tissue damage, and increase survival in animals infected with Y. pestis.

Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in aortic tissues from hypertensive rats

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3893-3900 ◽  
Author(s):  
Joseph Fomusi Ndisang ◽  
Lingyun Wu ◽  
Weimin Zhao ◽  
Rui Wang
Keyword(s):  
Heme Oxygenase ◽  
Macrophage Infiltration ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Vascular Tissues ◽  
Wistar Kyoto ◽  
And Function ◽  
Cardiovascular Functions

Abstract Heme oxygenase (HO) and carbon monoxide (CO) have been implicated in the modulation of various cardiovascular functions including blood pressure (BP) regulation. Up-regulating the HO/CO system lowers BP in young (8-week-old) but not in adult (20-week-old) spontaneously hypertensive rats (SHRs). The mechanisms for this selective effect are largely unknown. We investigated the effects of HO-1 inducer, hemin, on the HO/CO-soluble gyanylyl cyclase (sGC)/cGMP system in the aorta of prehypertensive (4-week-old) young and adult SHRs as well as age-matched Wistar-Kyoto rats (WKYs). Reduced expressions of HO-1, HO-2, and sGC proteins associated with depressed HO activity and cGMP levels were detected in young SHRs. These deficiencies were significantly reversed by hemin treatment. Macrophage infiltration of vascular tissues was more significant in adult SHRs than adult WKYs, but invisible in young SHRs and WKYs. Hemin treatment did not alter macrophage infiltration of vascular tissues in young SHRs. The same hemin administration resulted in a significant decrease in BP (from 148.6 ± 3.2 to 125.8 ± 2.6 mmHg, P < .01) in young SHRs, but not in prehypertensive or adult SHRs or WKYs of all ages. The HO inhibitor zinc protoporphyrin abrogated the hemin effect in young SHRs. Aortic tissues became desensitized to YC-1, an activator sGC, in adult SHRs. Thus, in young SHRs the expression and function of the HO/CO-sGC/cGMP system were suppressed, constituting a pathogenic mechanism for the development of hypertension. In adult SHRs, the HO/CO-sGC/cGMP system appeared normal, but desensitization of the sGC/cGMP pathway caused hypertension to prevail.

scholarly journals Targeting heme oxygenase-1 in early diabetic nephropathy in streptozotocin-induced diabetic rats

2016 ◽  
Vol 103 (4) ◽  
pp. 413-427 ◽  
Author(s):  
R Abo El Gheit ◽  
MN Emam
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Protoporphyrin Ix ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Stress Markers ◽  
Cobalt Protoporphyrin ◽  
Underlying Mechanisms

Diabetic nephropathy (DN) is one of the most common microvascular diabetic complications. This study was designed to evaluate the possible protective effect and underlying mechanisms of HO-1 induction in streptozotocin (STZ)-induced early DN in rats. The diabetic rats were divided into three groups: STZ-diabetic, cobalt protoporphyrin (CoPP)-treated diabetic, and zinc protoporphyrin IX (ZnPP)-treated diabetic groups. Compared to the STZ-diabetic group, CoPP-induced HO-1 upregulation improved the diabetic state and renal functional parameters, suppressed the renal proinflammatory marker, NF-κB, abrogated the elevated renal hydroxyprolin, and decreased the enhanced renal nicotinamide adenine dinucleotide phosphate oxidase activity with parallel reduction of urinary oxidative stress markers. On the contrary, treatment with ZnPP abrogated HO-1 levels, aggravated the diabetic condition with further increases in renal oxidative stress, fibrotic and inflammatory markers, and exacerbated renal dysfunction in diabetic animals. These findings suggest that the reduced diabetic renal injury upon HO-1 induction implicates the role of HO-1 induction as a potential treatment for DN.

Heme oxygenase-1 expression enhances vascular endothelial resistance to complement-mediated injury through induction of decay-accelerating factor: a role for increased bilirubin and ferritin

Blood ◽  
2009 ◽  
Vol 113 (7) ◽  
pp. 1598-1607 ◽  
Author(s):  
Anne R. Kinderlerer ◽  
Isabel Pombo Gregoire ◽  
Shahir S. Hamdulay ◽  
Faisal Ali ◽  
Rivka Steinberg ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Complement Activation ◽  
Ischemia Reperfusion ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Decay Accelerating Factor ◽  
Enhanced Sensitivity ◽  
Free Heme ◽  
Cobalt Protoporphyrin

Abstract Catabolism of free heme by heme oxygenase-1 (HO-1) generates carbon monoxide, biliverdin, and free iron (Fe). These end-products are responsible for much of the biologic activity of HO-1, including anti-inflammatory, antiapo-ptotic, antiproliferative, and antioxidant effects. We have identified an additional cytoprotective action, the regulation of complement activation, mediated via induction of decay-accelerating factor (DAF). Pharmacologic inhibition or short-interfering RNA (siRNA) depletion of HO-1 prevented induction of DAF expression in human endothelial cells. In contrast, HO-1 agonists hemin and cobalt protoporphyrin IX significantly increased DAF protein expression, reflecting an increase in transcription and steady-state mRNA. Adenoviral-mediated overexpression of HO-1 increased DAF expression, enhancing protection against C3 deposition and complement-mediated lysis, and this was reversed by DAF inhibitory monoclonal antibody (mAb) 1H4. Likewise, bilirubin, Fe chelation, and overexpression of heavy-chain ferritin all induced DAF expression in endothelial cells (EC). Analysis of cardiac endothelial cells isolated from Hmox1−/− mice revealed a 60% reduction in DAF expression compared with Hmox1+/+ EC, and Hmox1−/− cells showed enhanced sensitivity to complement. We propose that modulation of complement activation through induction of DAF represents an important component of the cytoprotective effects of HO-1 against vascular injury, such as that associated with posttransplant vasculopathy, allograft rejection, and ischemia reperfusion.

scholarly journals Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1

2016 ◽  
Vol 39 (2) ◽  
pp. 531-543 ◽  
Author(s):  
Jingang An ◽  
Tian Li ◽  
Yingying Dong ◽  
Zhengxiao Li ◽  
Jia Huo
Keyword(s):  
Heme Oxygenase ◽  
Therapeutic Option ◽  
Protoporphyrin Ix ◽  
Psoriatic Skin ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Keratinocyte Proliferation ◽  
Factor Α ◽  
Psoriatic Lesions

Background/Aims: Psoriasis is one of the most common inflammatory skin disorders, affecting 3% of the general population. Terminalia chebulanin (TC) is a polyphenolic compound that possesses antioxidant and anti-inflammatory activities. The current study was designed to investigate the effect of TC on psoriatic lesions. Methods: We examined the protective effect of TC against psoriatic lesions in mice and keratinocyte proliferation in HaCaT cells. Results: We found that TC exhibited potent anti-psoriatic activities, as evidenced by improvement of erythema and scaling scores, decrease of epidermal, ear and skinfold thickening, decrease of tumor necrosis factor α (TNFα), interleukin (IL)-17A, IL-23 and matrix metalloproteinase (MMP)-9 expression, and decrease of TBARS content and increase of GSH content in IMQ-treated mice, and decrease of keratinocyte proliferation, TNFα, IL-17A and IL-23 expression, and ROS level in M5-treated cells. All those effects induced by TC were inhibited by zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase (HO)-1, indicating that HO-1 was responsible the anti-psoriatic effect of TC. Moreover, TC inhibited the upregulation of p65 NF-κB under in vitro psoriatic condition. ZnPP suppressed TC-induced inhibition of p65 NF-κB expression. Overexpression of p65 NF-κB significantly suppressed TC-induced decrease of TNFα, IL-17A and IL-23 expression and keratinocyte proliferation, indicating that HO-1-mediated downregulation of NF-κB was involved in the anti-psoriatic effect of TC. Conclusions: The data demonstrate that TC may serve as a potential therapeutic option for psoriatic patients.

scholarly journals Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice

2006 ◽  
Vol 120 (3) ◽  
pp. 500-505 ◽  
Author(s):  
Kaeko Hirai ◽  
Tomonori Sasahira ◽  
Hitoshi Ohmori ◽  
Kiyomu Fujii ◽  
Hiroki Kuniyasu
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Heme Oxygenase ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
C57bl Mice

scholarly journals Zinc Protoporphyrin Upregulates Heme Oxygenase-1 in PC-3 Cells via the Stress Response Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Simon C. M. Kwok
Keyword(s):  
Stress Response ◽  
Protein Kinase ◽  
Heme Oxygenase ◽  
Kinase Inhibitors ◽  
Protoporphyrin Ix ◽  
Competitive Inhibitor ◽  
Protein Kinase Inhibitors ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Transcriptional Level

Zinc protoporphyrin IX (ZnPP), a naturally occurring molecule formed in iron deficiency or lead poisoning, is a potent competitive inhibitor of heme oxygenase-1 (HO-1). It also regulates expression of HO-1 at the transcriptional level. However, the effect of ZnPP on HO-1 expression is controversial. It was shown to induce HO-1 expression in some cells, but suppress it in others. The objective of this study is to investigate the effect of ZnPP on HO-1 expression in prostate cancer PC-3 cells. Incubation of PC-3 cells with 10 μM ZnPP for 4 h showed only a slight induction of HO-1 mRNA and protein, but the induction was high after 16 h and was maintained through 48 h of incubation. Of all the known responsive elements in the HO-1 promoter, ZnPP activated mainly the stress response elements. Of the various protein kinase inhibitors and antioxidant tested, only Ro 31-8220 abrogated ZnPP-induced HO-1 expression, suggesting that activation of HO-1 gene by ZnPP may involve protein kinase C (PKC). The involvement of PKCα,β,δ,η,θ, andζisoforms was ruled out by the use of specific inhibitors. The isoform of PKC involved and participation of other transcription factors remain to be studied.

scholarly journals Resistance Exercise Induces Heme Oxygenase-1 Expression to Promote Macrophage Polarization and Accelerate Catheter-related Thrombolysis and Recanalization in Rats

2021 ◽  
Author(s):  
Jiani Wei ◽  
Huihan Zhao ◽  
Qingjuan Jiang ◽  
Cui Wen ◽  
Xinxin Huang ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Heme Oxygenase ◽  
Quantitative Polymerase Chain Reaction ◽  
Macrophage Polarization ◽  
Protoporphyrin Ix ◽  
Major Complication ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Level Increase ◽  
Cobalt Protoporphyrin

Abstract IntroductionCatheter-related thrombosis (CRT) is a major complication of central venous catheters. Resistance exercise to prevent CRT formation has been demonstrated, but there are few studies of CRT dissolution and recanalization. In this study, we focused on resistance exercise, heme oxygenase-1 (HO-1), and macrophage polarization to investigate the mechanism of resistance exercise accelerating thrombolysis and recanalization, providing a theoretical basis for resistance exercise adjuvant therapy of CRT.MethodsA rat CRT model was established and Intervened with resistance exercise and injection of HO-1 agonist cobalt protoporphyrin (COPP) and the inhibitor tin protoporphyrin IX(SnPP).Thrombolysis and recanalization were observed by hematoxylin and eosin(H&E). Neovascularization was detected by immunohistochemical CD31 staining. The levels of HO-1, IL-6, and IL-10 in the rat sera were determined by enzyme-linked immunosorbent assay (ELISA). The relative expression levels of HO-1, Arg-1, HO-1, CD206, and CD80 mRNA were detected by quantitative polymerase chain reaction (qPCR). The colocalization expression of HO-1 with CD206 and CD86 were detected by immunofluorescence.ResultsResistance exercise for 28 days could induce HO-1 expression, decrease IL-6 level, increase IL-10 level, increase Arg-1 and CD206 expression, decrease INOS and CD80 expression, and increase CD31 expression, and the co-localization expression of HO-1 and CD206 was significantly higher than that of HO-1 and CD86.ConclusionAfter 28 days of resistance exercise, mechanical stimulation can mediate the expression of HO-1 in macrophages, promote the polarization of M2 macrophages, exert the effects of anti-inflammation and promoting angiogenesis, and accelerate the dissolution and recanalization of CRT.

scholarly journals Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells

Oncogene ◽  
2004 ◽  
Vol 23 (2) ◽  
pp. 503-513 ◽  
Author(s):  
Zhi-Min Liu ◽  
George G Chen ◽  
Enders KW Ng ◽  
Wai-Keung Leung ◽  
Joseph JY Sung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells
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