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HO-1 Protein (ho-1 + protein)
Selected AbstractsCurcumin-induced fibroblast apoptosis and in vitro wound contraction are regulated by antioxidants and heme oxygenase: implications for scar formationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2009A. Scharstuhl Abstract Fibroblast apoptosis plays a crucial role in normal and pathological scar formation and therefore we studied whether the putative apoptosis-inducing factor curcumin affects fibroblast apoptosis and may function as a novel therapeutic. We show that 25-,M curcumin causes fibroblast apoptosis and that this could be inhibited by co-administration of antioxidants N -acetyl- l -cysteine (NAC), biliverdin or bilirubin, suggesting that reactive oxygen species (ROS) are involved. This is supported by our observation that 25-,M curcumin caused the generation of ROS, which could be completely blocked by addition of NAC or bilirubin. Since biliverdin and bilirubin are downstream products of heme degradation by heme oxygenase (HO), it has been suggested that HO-activity protects against curcumin-induced apoptosis. Interestingly, exposure to curcumin maximally induced HO-1 protein and HO-activity at 10,15 ,M, whereas, at a concentration of >20-,M curcumin HO-1-expression and HO-activity was negligible. NAC-mediated inhibition of 25-,M curcumin-induced apoptosis was demonstrated to act in part via restored HO-1-induction, since the rescuing effect of NAC could be reduced by inhibiting HO-activity. Moreover pre-induction of HO-1 using 5-,M curcumin protected fibroblasts against 25-,M curcumin-induced apoptosis. On a functional level, fibroblast-mediated collagen gel contraction, an in vitro wound contraction model, was completely prevented by 25-,M curcumin, while this could be reversed by co-incubation with NAC, an effect that was also partially HO-mediated. In conclusion, curcumin treatment in high doses (>25 ,M) may provide a novel way to modulate pathological scar formation through the induction of fibroblast apoptosis, while antioxidants, HO-activity and its effector molecules act as a possible fine-tuning regulator. [source] siRNA-mediated Knockdown of the Heme Synthesis and Degradation Pathways: Modulation of Treatment Effect of 5-Aminolevulinic Acid-based Photodynamic Therapy in Urothelial Cancer Cell LinesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2009Makito Miyake Photodynamic therapy mediated by 5-aminolevulinic acid (ALA-PDT) has been developed as a therapeutic modality for refractory superficial bladder cancers. Here, in experiments using urothelial cancer cell lines, we investigated the effects of siRNA modulating heme-synthetic and degradation pathways for ALA-PDT. Targeted knockdown of ferrochelatase (FECH) suppressed heme synthesis and significantly increased intracellular protoporphyrin IX (PpIX) accumulation, leading to enhanced phototoxicity in four of five cell lines. Heme oxygenase-1 (HO-1) is recognized as important for cytoprotection against oxidative stress such as PDT. Targeted knockdown of HO-1 leads to decreased intracellular PpIX accumulation, resulting in a failure to enhance ALA-PDT effect in four cell lines. Knockdown of HO-1 caused marked growth inhibition in UM-UC-2 overexpressing HO-1, whereas no inhibitory effect was observed in UM-UC-3 lacking HO-1 expression. Moreover, HO-1 protein levels and (GT)n repeat polymorphism of the HO-1 gene promoter region were examined with the implication that the constitutive expressions of HO-1 protein were associated with a shorter (GT)n repeat. Our results suggested that (1) FECH siRNA improved the phototoxicity of ALA-PDT, (2) overexpression of HO-1 was associated with shorter (GT)n repeat of the promoter region, and (3) siRNA-mediated knockdown of HO-1 could suppress the growth of bladder cancer cells overexpressing HO-1. [source] Expression and Activity of Heme Oxygenase-1 in Artificially Induced Low-Flow Priapism in Rat Penile TissuesTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2008Yong Chun Jin ABSTRACT Introduction., The inducible isoform of heme oxygenase (HO)-1 regulates the vascular smooth muscle tone and responds to hypoxia. Aim., To investigate the role of HO-1 in a low-flow priapism. Materials and Methods., Sixty male Sprague-Dawley rats were divided into five groups of six rats each. Each group of rats was sacrificed at 0 hour (group 1, control), 4 hours (group 2), 8 hours (group 3), 12 hours (group 4), and 24 hours (group 5) after inducing an artificial veno-occlusive priapism. The changes of the expression and activity of HO-1, and the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and levels of cyclic guanosine monophosphate in the penis were examined in a low-flow priapism. In addition, the HO-1 expression level in the aortas from each group was simultaneously measured to determine whether the changes in HO-1 were systemic. Main Outcome Measures., The expression and activity of HO-1 was examined in artificially induced veno-occlusive priapism in rat penile tissues. Results., The expression of the HO-1 protein and the HO-1 enzyme activities in the penile tissues were gradually increased as time increased from 0 to 24 hours (P < 0.01). HO-1 immunoreactivities were localized in the endothelial layer of the cavernosal sinusoids. The expression of iNOS were also increased at 12 and 24 hours. The cyclic guanosine monophosphate level was also significantly increased at 24 hours (P < 0.05). However, the expression of the eNOS protein showed no statistically significant change with time, and the expression of the HO-1 protein in the aorta also showed no significant change with time. Conclusions., A higher induction of HO-1 with time was observed in artificially induced veno-occlusive priapism, which might play a protective role against hypoxic injury. However, this may also play an important role in the vicious circle observed in a low-flow priapism. Jin YC, Gam SC, Jung JH, Hyun JS, Chang KC, and Hyun JS. Expression and activity of heme oxygenase-1 in artificially induced low-flow priapism in rat penile tissues. J Sex Med 2008;5:1876,1882. [source] Effect of HO-1 cDNA-liposome complex transfer on erectile signalling of aged ratsANDROLOGIA, Issue 3 2009M. T. Abdel Aziz Summary This work aimed to assess the efficacy of haeme oxygenase-1 (HO-1) cDNA-liposome complex transfer as a mediator of erectile signalling in aged rats. One hundred and fifty aged white albino rats were equally divided into five groups: controls, rats receiving lipofectamine, rats receiving intracorporeal HO-1 cDNA-lipsome complex, rats receiving HO-1 cDNA-liposome complex plus nitric oxide synthase (NOS) inhibitor, and rats receiving HO-1 cDNA-liposome complex plus HO inhibitor. Six rats were killed from each group after 12, 24 and 48 h, and after1 and 2 weeks. In dissected cavernous tissues, the following were assessed: HO-1 gene expression, Western blot for HO-1, HO enzyme activity, cGMP and histopathology. The results showed that HO-1 cDNA-liposome complex transfer led to a significant increase in cavernous tissue HO-1 protein, HO-1 gene expression, HO enzyme activity and cGMP up to 1 week. NOS inhibition exhibited no effect on HO-1 gene enhancement of cavernous tissue HO enzyme activity or cGMP, whereas inhibition of HO significantly decreased these parameters. Histopathology of cavernous tissue demonstrated a significant dilatation of helicine arteries in HO-1 cDNA-liposome complex treated group after 48 h compared with the controls. It is concluded that HO-1 cDNA-liposome complex transfer augments cavernous tissue cGMP with subsequent sinusoidal relaxation. [source] The HIV protease inhibitor ritonavir synergizes with butyrate for induction of apoptotic cell death and mediates expression of heme oxygenase-1 in DLD-1 colon carcinoma cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2004Heiko Mühl The protease inhibitor ritonavir is an integral part of current antiretroviral therapy targeting human immunodeficiency virus. Recent studies demonstrate that ritonavir induces apoptotic cell death with high efficiency in lymphoblastoid cell lines. Moreover, ritonavir can suppress activation of the transcription factor nuclear factor- ,B and is an inhibitor of interleukin-1, and tumor necrosis factor- , production in peripheral blood mononuclear cells. Thus, ritonavir appears to have anti-inflammatory properties. In the present study, we investigated in DLD-1 colon carcinoma cell effects of ritonavir on apoptotic cell death and expression of heme oxygenase-1 (HO-1), an anti-inflammatory enzyme that may be critically involved in the modulation of colonic inflammation. Compared to unstimulated control, ritonavir resulted in a moderate increase in the rate of apoptotic cell death as observed after 20 h of incubation. Notably, ritonavir potently synergized with the short-chain fatty acid butyrate for induction of caspase-3-dependent apoptosis in DLD-1 cells. Ritonavir enhanced mRNA and protein expression of HO-1 in DLD-1 cells. Ritonavir-induced HO-1 protein was suppressed by SB203580 or SB202190 and preceded by immediate upregulation of cellular c-Fos and c-Jun protein levels. This process was associated with induction of activator protein-1 as detected by electrophoretic mobility shift analysis. The present data suggest that ritonavir has the potential to curb colon carcinogenesis by reducing cell growth via mechanisms that include apoptosis and by simultaneously modulating colonic inflammation via induction of anti-inflammatory HO-1. British Journal of Pharmacology (2004) 143, 890,898. doi:10.1038/sj.bjp.0706023 [source] BEHAVIOUR OF THE ANTI-OXIDANT DEFENCE SYSTEM AND HEME OXYGENASE-1 PROTEIN EXPRESSION IN FRUCTOSE-HYPERTENSIVE RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2006Ariel H Polizio SUMMARY 1Addition of fructose to a rat diet for various periods of time leads to hypertension, hyperinsulinaemia and dyslipidaemia and provides a model for testing oxidative stress parameters in the animals. 2In the present study, oxidative stress generation, the soluble and enzymatic defence system and heme oxygenase-1 (HO-1) protein expression were investigated in the heart, liver and kidney of rats fed fructose for a period of 1 or 8 months. 3Compared with the control group, fructose-hypertensive rats showed increased in lipid peroxidation only in the heart after both 1 and 8 months of fructose treatment. Changes in the behaviour of the soluble and enzymatic defence system and HO-1 protein expression were different depending on the organ. Increased or unaltered activities of anti-oxidant enzymes were found in the liver and kidney, respectively. Induction of HO-1 prevented the generation of oxidative stress in the liver, where the activity of anti-oxidant defence enzymes was not reduced. Increased expression of HO-1 protein was not able to prevent the generation of oxidative stress in the heart, where fructose treatment diminished the activity of anti-oxidant enzymes. 4The results of the present study demonstrate that upregulation of HO-1 may prevent the generation of oxidative stress only when the anti-oxidant defence system is still operative. [source] | ||||||||||