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

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 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 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 Carbon Monoxide Regulates Macrophage Differentiation and Polarization toward the M2 Phenotype through Upregulation of Heme Oxygenase 1

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3444
Author(s):  
In-Soon Kang ◽  
Rang-Ie Kim ◽  
Chaekyun Kim
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Bone Marrow Cells ◽  
Protoporphyrin Ix ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Macrophage Differentiation ◽  
Murine Bone Marrow ◽  
Arginase 1 ◽  
M2 Phenotype

Carbon monoxide (CO) is generated by heme oxygenase (HO), and HO-1 is highly induced in monocytes and macrophages upon stimulation. Monocytes differentiate into macrophages, including pro-inflammatory (M1) and anti-inflammatory (M2) cells, in response to environmental signals. The present study investigated whether CO modulates macrophage differentiation and polarization, by applying the CO-releasing molecule-3 (CORM-3). Results showed that murine bone marrow cells are differentiated into macrophages by CORM-3 in the presence of macrophage colony-stimulating factor. CORM-3 increases expressions of macrophage markers, including F4/80 and CD11b, and alters the cell morphology into elongated spindle-shaped cells, which is a typical morphology of M2 cells. CORM-3 upregulates the expressions of genes and molecules involved in M2 polarization and M2 phenotype markers, such as STAT6, PPARγ, Ym1, Fizz1, arginase-1, and IL-10. However, exposure to CORM-3 inhibits the iNOS expression, suggesting that CO enhances macrophage differentiation and polarization toward M2. Increased HO-1 expression is observed in differentiated macrophages, and CORM-3 further increases this expression. Hemin, an HO-1 inducer, results in increased macrophage differentiation, whereas the HO-1 inhibitor zinc protoporphyrin IX inhibits differentiation. In addition, CORM-3 increases the proportion of macrophages in peritoneal exudate cells and enhances the expression of HO-1 and arginase-1 but inhibits iNOS. Taken together, these results suggest that the abundantly produced CO in activated macrophages enhances proliferation, differentiation, and polarization toward M2. It will probably help clear apoptotic cells, resolve inflammation, and promote wound healing and tissue remodeling.

Smad7 sensitizes A549 lung cancer cells to cisplatin-induced apoptosis through heme oxygenase-1 inhibition

2012 ◽  
Vol 420 (2) ◽  
pp. 288-292 ◽  
Author(s):  
Woo-Kwang Jeon ◽  
Hey-Young Hong ◽  
Won-Chan Seo ◽  
Kyu-Hyoung Lim ◽  
Hui-Young Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Heme Oxygenase ◽  
Lung Cancer Cells ◽  
Heme Oxygenase 1 ◽  
Induced Apoptosis ◽  
A549 Lung

The Effect of Inhibition of Heme Oxygenase-1 on Chemosensitivity of Cisplatin in Lung Cancer Cells

2007 ◽  
Vol 62 (1) ◽  
pp. 33 ◽  
Author(s):  
So-Young Kim ◽  
Eun-Jung Kim ◽  
Hye-Yeon Jang ◽  
Ki-Eun Hwang ◽  
Jung-Hyun Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Heme Oxygenase ◽  
Lung Cancer Cells ◽  
Heme Oxygenase 1

Abstract TP376: Heme Oxygenase-1 is Essential for Hematoma Clearance After Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Liyan Zhang ◽  
Xiurong Zhao ◽  
Guanghua Sun ◽  
Jaroslaw Aronowski
Keyword(s):  
Intracerebral Hemorrhage ◽  
Rat Brain ◽  
Heme Oxygenase ◽  
Functional Recovery ◽  
Protoporphyrin Ix ◽  
Neuronal Injury ◽  
Neurological Deficits ◽  
Sublethal Dose ◽  
Heme Oxygenase 1 ◽  
Secondary Brain Injury

Background: After intracerebral hemorrhage (ICH), the red blood cells (RBC) and their hemolytic products within brain hematoma trigger adverse biochemical events, leading to secondary brain injury and neurological deficits. Thus, efficient removal of hematoma components is essential for achieving inflammation resolution and functional recovery. The inducible heme-oxygenase (HO-1) is a key rate-limiting enzyme that catabolizes heme into iron, CO, and biliverdin. The present study investigated the role of HO-1 in microglia/macrophages (MΦ)-mediated phagocytosis of RBC; and also assessed the spatial and temporal expression of HO-1 in ICH-affected brain, as well as its possible role in the clearance of hematoma components following ICH modeled in rodents. Methods and Results: First, we employed the rat brain MΦ. Upon exposing to RBC, MΦ phagocytize RBC; and HO-1 was induced during this process. Co-incubating tin-protoporphyrin IX (SnPP, a competitive HO-1 inhibitor) with RBC significantly delayed RBC internalization by MΦ. Removal of SnPP from the culture medium led to a rapid recovery of MΦ’s phagocytic function, suggesting that SnPP-induced inhibition is a reversible process. Subjecting neuron-microglia co-cultures to RBC plus sublethal dose of oxygen-deprivation (an ICH-like insult) triggered neuronal injury, as assessed using neurofilament degradation assay and loss of NeuN-positive cells; and addition of SnPP further aggravated the neuronal injury. Additional studies showed that after ICH, HO-1 is up-regulated in hematoma-affected rat brain tissues starting from 6h, reaching the maximum level at 3-7days, and persisting for at least 10 days after ICH. Double immunohistochemistry of HO-1 and brain cell markers shows that the most HO-1-positive cells are Iba1-positive MΦ. Administration of SnPP for 7 days, (7.5 mg/kg, ip, twice a day) delayed hematoma clearance by 27.8% and significantly impaired the functional recovery, as measured 7 days after ICH. Histological analyses showed that there are more TUNEL-positive neurons in the hematoma-affected brain tissue in SnPP-treated mouse brains. Conclusion: Our study suggests that HO-1 is essential for phagocytosis of RBC by MΦ, which is critical for endogenous clearance of hematoma after ICH.

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