Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis

Vulapalli, Sreesatya Raju; Chen, Zhongyi; Chua, Balvin H.L.; Wang, Ting‐Chung; Liang, Chang‐seng

doi:10.1152/ajpheart.00133.2002

Cited by 123 publications

(99 citation statements)

References 37 publications

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“…Constitutive or regulated overexpression of HO-1 in hearts or organ transplants is capable of reducing cell death caused by ischemia-reperfusion injury. 18,[33][34][35][36] This notion is in agreement with our recent report that hypoxia-inducible expression of HO-1 conferred significant protection to the heart following myocardial ischemia. 37 The vigilant vector system targets tissue selectively, unlike other HRE-SV40-based gene switch systems which are not tissue selective.…”

Section: Discussionsupporting

confidence: 92%

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Tang

Tang²,

Zhang

et al. 2005

Gene Ther

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Section: Discussionsupporting

confidence: 92%

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Tang

Tang²,

Zhang

et al. 2005

Gene Ther

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“…The antiapoptotic effect of HO-1 is reversed in the presence of HO-1 inhibitors or in cells overexpressing antisense HO-1 (Petrache et al, 2000). Inhibition of apoptosis following the expression of HO-1 has also been reported in animal models of inflammation, ischemia-reperfusion, hypoxia, and organ transplantation while inhibition of HO-1 activity or deletion of the HO-1 gene promotes apoptosis in these animal models (Hancock et al, 1998;Soares et al, 1998;Yet et al, 1999;Ke et al, 2002;Vulapalli et al, 2002).…”

Section: Ho-1 and Cell Deathmentioning

confidence: 91%

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

Durante

2003

Journal Cellular Physiology

143

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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO-1 originally centered on its heme-degrading function, recent findings indicate that HO-1 exerts other biologically important actions. Emerging evidence suggests that HO-1 plays a critical role in growth regulation. Deletion of the HO-1 gene or inhibition of HO-1 activity results in growth retardation and impaired fetal development, whereas HO-1 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO-1 are not well established, HO-1 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO-1 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO-1 are highly variable and may reflect a role for HO-1 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO-1 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO-1 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO-1 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders.

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“…Three HO isoforms have been identified. The dominant isoform in muscle is HO-1, which is induced by stressful and inflammatory stimuli (13). Interestingly, it has been reported that HO-1 mRNA is lower in patients with type 2 diabetes compared with healthy control subjects (14).…”

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confidence: 99%

ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor δ (PPARδ) Stimulation

Woo

Massett

Shishido

et al. 2006

Journal of Biological Chemistry

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Peroxisome proliferator-activated receptors (PPAR) decrease the production of cytokine and inducible nitric-oxide synthase (iNOS) expression, which are associated with aging-related inflammation and insulin resistance. Recently, the involvement of the induction of heme oxygenase-1 (HO-1) in regulating inflammation has been suggested, but the exact mechanisms for reducing inflammation by HO-1 remains unclear. We found that overexpression of HO-1 and [Ru(CO) 3 Cl 2 ] 2 , a carbon monoxide (CO)-releasing compound, increased not only ERK5 kinase activity, but also its transcriptional activity measured by luciferase assay with the transfection of the Gal4-ERK5 reporter gene. This transcriptional activity is required for coactivation of PPAR␦ by ERK5 in C2C12 cells. [Ru(CO) 3 Cl 2 ] 2 activated PPAR␦ transcriptional activity via the MEK5/ERK5 signaling pathway. The inhibition of NF-B activity by ERK5 activation was reversed by a dominant negative form of PPAR␦ suggesting that ERK5/PPAR␦ activation is required for the anti-inflammatory effects of CO and HO-1. Based on these data, we propose a new mechanism by which CO and HO-1 mediate anti-inflammatory effects via activating ERK5/PPAR␦, and ERK5 mediates CO and HO-1-induced PPAR␦ activation via its interaction with PPAR␦.Muscle wasting is a major feature of the cachexia associated with diverse pathologies such as cancer, sepsis, diabetes, and aging (1). Several cytokines have been implicated in the pathogenesis of muscle wasting, most notably TNF-␣, 2 a pro-inflammatory cytokine that was originally called "cachectin" (1). In addition, aging-related chronic low grade inflammation by TNF-␣ plays an important role in insulin resistance (2). It has been proposed that chronic inflammation by TNF-␣-mediated NF-B activation and subsequent inducible nitric-oxide synthase (iNOS) induction relates to muscle wasting and insulin resistance as we will explain below. Cai et al. (3) have shown that activation of NF-B, through muscle-specific transgenic expression of activated IB kinase ␤ (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-B through expression of IB suppressor (MISR), and denervation and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-B inhibition in MISR mice, which is consistent with a critical role for NF-B in the pathology of muscle wasting, especially in diabetes and during the process of aging (3). Recent studies suggest the involvement of iNOS in the pathogenesis of insulin resistance (4, 5). First, most inducers of insulin resistance, including obesity (6), free fatty acids (7), hyperglycemia (8, 9), TNF-␣, oxidative stress, and endotoxin, increase iNOS expression. Second, iNOS mediates the impaired insulin-stimulated glucose uptake by treatment with TNF-␣ and lipopolysaccharide in cultured muscle cells (10). iNOS expression is elevated in skeletal muscle of patients with type 2 diabetes (11, 12), and high fat diet-induced...

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Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis

Cited by 123 publications

References 37 publications

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Heme oxygenase‐1 in growth control and its clinical application to vascular disease

ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor δ (PPARδ) Stimulation

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