Mitochondrial and Cellular Heme-Dependent Proteins as Targets for the Bioactive Function of the Heme Oxygenase/Carbon Monoxide System
Université Paris 7, Faculté de Medicine, site Xavier Bichat, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France. Antioxidants and Redox Signaling
(Impact Factor: 7.41).
01/2008; 9(12):2139-55. DOI: 10.1089/ars.2007.1803
The toxic effect of high concentrations of CO gas in living organisms is coherently typified at biochemical levels by the high affinity of CO for hemoglobin and cytochromes, heme-dependent proteins that are indispensable for oxygen transport and mitochondrial respiration. However, the basal production of CO during heme degradation and the ability of heme oxygenase-1 (HO-1) to increase CO availability pose the question of how this gaseous molecule interacts with metal centers within the intracellular milieu to serve as one of the most unconventional signaling mediators. Emerging evidence indicates that the diverse and multifaceted beneficial effects exerted by "low concentrations" of CO cannot be explained solely by the activation of classic prototypic targets (i.e., guanylate cyclase/potassium channels) but entails the dynamic and concerted activation/inhibition of a group of CO-responsive proteins. As the complexity of the temporal and spatial action of CO is progressively being appreciated, this review aims to (a) highlight the current knowledge on certain metal-containing proteins that interact directly with CO; (b) analyze the latest notions on their functional role in response to CO; and finally (c) propose a rational view on the mode these CO targets may interrelate with and be regulated by the HO/CO pathway.
Available from: Rehana Leak
- "Some authors have suggested that Hsp32 might be destructive in these conditions because it breaks down heme into ferrous iron, potentially increasing the risk for Fenton chemistry and iron toxicity (Schipper 2011). Indeed, heme-derived iron and carbon monoxide may both increase the risk for oxidative stress (Desmard et al. 2007; Zhang and Piantadosi 1992). On the other hand, coinduction of apoferritin appears to limit Hsp32 toxicity (Dennery 2000; Ryter and Tyrrell 2000), and many studies have verified that Hsp32 is protective (Calabrese et al. 2009; Jazwa and Cuadrado 2010; Zhang et al. 2013). "
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ABSTRACT: Many members of the heat shock protein family act in unison to refold or degrade misfolded proteins. Some heat shock proteins also directly interfere with apoptosis. These homeostatic functions are especially important in proteinopathic neurodegenerative diseases, in which specific proteins misfold, aggregate, and kill cells through proteotoxic stress. Heat shock protein levels may be increased or decreased in these disorders, with the direction of the response depending on the individual heat shock protein, the disease, cell type, and brain region. Aging is also associated with an accrual of proteotoxic stress and modulates expression of several heat shock proteins. We speculate that the increase in some heat shock proteins in neurodegenerative conditions may be partly responsible for the slow progression of these disorders, whereas the increase in some heat shock proteins with aging may help delay senescence. The protective nature of many heat shock proteins in experimental models of neurodegeneration supports these hypotheses. Furthermore, some heat shock proteins appear to be expressed at higher levels in longer-lived species. However, increases in heat shock proteins may be insufficient to override overwhelming proteotoxic stress or reverse the course of these conditions, because the expression of several other heat shock proteins and endogenous defense systems is lowered. In this review we describe a number of stress-induced changes in heat shock proteins as a function of age and neurodegenerative pathology, with an emphasis on the heat shock protein 70 (Hsp70) family and the two most common proteinopathic disorders of the brain, Alzheimer's and Parkinson's disease.
Journal of Cell Communication and Signaling 09/2014; 8(4). DOI:10.1007/s12079-014-0243-9
Available from: Rehana Leak
- "HO1 is also increased in astrocytes in Parkinson's disease and is present in Lewy bodies (Schipper et al. 1998). Some have argued that these changes are pathogenic because HO1 also breaks down heme into ferrous iron, increasing the risk for Fenton chemistry and iron toxicity (Schipper 2011) Although heme-derived iron and carbon monoxide may increase oxidative stress (Zhang and Piantadosi 1992, Desmard et al. 2007), co-induction of apoferritin synthesis is thought to limit HO1 toxicity (Dennery 2000, Ryter and Tyrrell 2000). Furthermore, the vast majority of experimental studies of HO1 manipulation demonstrate that HO1 is protective (Calabrese et al. 2009, Jazwa and Cuadrado 2010, Zhang et al. 2013). "
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ABSTRACT: Many heat shock proteins are chaperones that help refold or degrade misfolded proteins and battle apoptosis. Because of their capacity to protect against protein misfolding, they may help keep diseases of aging at bay. A few reports have examined heat shock proteins (eg. Hsp25, Hsp60, Hsp70, and heat shock cognate 70 or Hsc70) as a function of age in the striatum and nigra. In the present study, we examined the impact of aging on Hsp25, heme oxygenase 1 (HO1 or Hsp32), Hsp40, Hsp60, Hsc70, Hsc/Hsp70 interacting protein (Hip), 78 kDa glucose-regulated protein (GRP78), Hsp90, and ubiquitinated proteins in the nigra and striatum of the female rat by infrared immunoblotting. Female animals are not typically examined in aging studies, adding further to the novelty of our study. Striatal HO1 and Hsp40 were both higher in middle-aged females than in the oldest group. Hsp60 levels were also highest in middle age in the nigra, but were highest in the oldest animals in the striatum. Striatal levels of Hsc70 and the co-chaperone Hip were lower in the oldest group relative to the youngest animals. In contrast, Hsp25 rose with advancing age in both regions. Hsp25 was also colocalized with tyrosine hydroxylase in nigral neurons. Ubiquitinated proteins exhibited a trend to rise in the oldest animals in both regions, and K48 linkage-specific ubiquitin rose significantly from 4-6 to 16-19 months in the striatum. Our study reveals a complex array of age-related changes in heat shock proteins. Furthermore, the age-related rises in some proteins, such as Hsp25, may reflect endogenous adaptations to cellular stress.
Cell and Tissue Research 04/2014; 357(1). DOI:10.1007/s00441-014-1852-6 · 3.57 Impact Factor
Available from: Lian Li
- "Although Hsp32/HO-1 in testis after hyperthermia or other treatments has been intensely investigated, the molecular mechanisms regarding the anti-apoptotic role of Hsp32/HO-1 are poorly understood. Many of the protective effects of Hsp32/HO-1 induction have been attributed to two of its products, CO (Otterbein et al., 2003a; Maines and Gibbs, 2005; Desmard et al., 2007; Bilban et al., 2008) or bilirubin (Stocker et al., 1987; Clark et al., 2000; Erario et al., 2002). Hsp32/HO-1 has anti-inflammatory, antiapoptotic , and anti-proliferative effects in different systems (Morse and Choi, 2002; Bilban et al., 2008). "
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ABSTRACT: Heat shock protein 32 (Hsp32)/ heme oxygenase-1 (HO-1) is believed to represent a key enzyme for the protection of cells against stress. The anti-apoptotic effect of Hsp32/HO-1 has been attributed to its product carbon monoxide (CO) in many types of cells; however, whether the anti-apoptotic mechanism plays a role in Sertoli cells is not yet clear. We hypothesize that Hsp32/HO-1 and CO generated from Hsp32/HO-1 provide survival advantages in Sertoli cells by preventing apoptosis under heat exposure. Therefore, the aim of our investigations was to identify the possible roles of Hsp32/HO-1 in hyperthermia stress Sertoli cells. After treatment of cultured mouse Sertoli cells with hyperthermia or/and Hsp32/HO-1 activator Hemin, we evaluated apoptosis by annexin V-FITC and caspase-3 activation. In addition, we analyzed the Hsp32/HO-1-derived CO contents in cultured media and cyclic guanosine monophosphate (cGMP) production by enzyme-linked immunosorbent assay (ELISA). The results showed that the hyperthermia induced Sertoli cells apoptosis, while preincubation with Hemin suppressed Sertoli cell apoptosis induced by hyperthermia treatment. Hyperthermia or/and Hemin increase Hsp32/HO-1 gene expression and the production of CO which, in turn, stimulates the generation of cGMP. Taken together, our results suggest that Hsp32/HO-1 is a protective factor in heat-stressed Sertoli cells, and that CO generated from Hsp32/HO-1 is involved in the anti-apoptotic pathway.
Cell Biology International 01/2014; 38(1). DOI:10.1002/cbin.10177 · 1.93 Impact Factor
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