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001-es BibID:BIBFORM051960
Első szerző:Bolisetty, Subhashini
Cím:Mitochondria-targeted heme oxygenase-1 decreases oxidative stress in renal epithelial cells / Subhashini Bolisetty, Amie Traylor, Abolfazl Zarjou, Michelle S. Johnson, Gloria A. Benavides, Karina Ricart, Ravindra Boddu, Ray D. Moore, Aimee Landar, Stephen Barnes, Victor Darley-Usmar, Anupam Agarwal
Dátum:2013
ISSN:1931-857X 1522-1466
Megjegyzések:Mitochondria are both a source and target of the actions of reactive oxygen species and possess a complex system of inter-related antioxidants that control redox signaling and protect against oxidative stress. Interestingly, the antioxidant enzyme heme oxygenase-1 (HO-1) is not present in the mitochondria despite the fact that the organelle is the site of heme synthesis and contains multiple heme proteins. Detoxification of heme is an important protective mechanism since the reaction of heme with hydrogen peroxide generates pro-oxidant ferryl species capable of propagating oxidative stress and ultimately cell death. We therefore hypothesized that a mitochondrially localized HO-1 would be cytoprotective. To test this, we generated a mitochondria-targeted HO-1 cell line by transfecting HEK293 cells with a plasmid construct containing the manganese superoxide dismutase mitochondria leader sequence fused to HO-1 cDNA (Mito-HO-1). Nontargeted HO-1-overexpressing cells were generated by transfecting HO-1 cDNA (HO-1) or empty vector (Vector). Mitochondrial localization of HO-1 with increased HO activity in the mitochondrial fraction of Mito-HO-1 cells was observed, but a significant decrease in the expression of heme-containing proteins occurred in these cells. Both cytosolic HO-1- and Mito-HO-1-expressing cells were protected against hypoxia-dependent cell death and loss of mitochondrial membrane potential, but these effects were more pronounced with Mito-HO-1. Furthermore, decrement in production of tricarboxylic acid cycle intermediates following hypoxia was significantly mitigated in Mito-HO-1 cells. These data suggest that specific mitochondrially targeted HO-1 under acute pathological conditions may have beneficial effects, but the selective advantage of long-term expression is constrained by a negative impact on the synthesis of heme-containing mitochondrial proteins.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:American Journal of Physiology. Renal Physiology. - 305 : 3 (2013), p. F255-F264. -
További szerzők:Traylor, Amie Zarjou, Abolfazl (1979-) (kutató orvos) Johnson, Michelle S. Benavides, Gloria A. Ricart, Karina Boddu, Ravindra Moore, Ray D. Landar, Aimee Barnes, Stephen Darley-Usmar, Victor Agarwal, Anupam
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001-es BibID:BIBFORM077162
035-os BibID:(WoS)000457627800001 (Scopus)85062188852 (cikkazonosító)131
Első szerző:Zarjou, Abolfazl (kutató orvos)
Cím:Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury / Zarjou Abolfazl, Black Laurence M., McCullough Kayla R., Hull Travis D., Esman Stephanie K., Boddu Ravindra, Varambally Sooryanarayana, Chandrashekar Darshan S., Feng Wenguang, Arosio Paolo, Poli Maura, Balla Jozsef, Bolisetty Subhashini
Dátum:2019
ISSN:1664-3224
Megjegyzések:Despite the prevalence and recognition of its detrimental impact, clinical complications of sepsis remain a major challenge. Here, we investigated the effects of myeloid ferritin heavy chain (FtH) in regulating the pathogenic sequelae of sepsis. We demonstrate that deletion of myeloid FtH leads to protection against lipopolysaccharide-induced endotoxemia and cecal ligation and puncture (CLP)-induced model of sepsis as evidenced by reduced cytokine levels, multi-organ dysfunction and mortality. We identified that such protection is predominantly mediated by the compensatory increase in circulating ferritin (ferritin light chain; FtL) in the absence of myeloid FtH. Our in vitro and in vivo studies indicate that prior exposure to ferritin light chain restrains an otherwise dysregulated response to infection. These findings are mediated by an inhibitory action of FtL on NF-?B activation, a key signaling pathway that is implicated in the pathogenesis of sepsis. We further identified that LPS mediated activation of MAPK pathways, specifically, JNK, and ERK were also reduced with FtL pre-treatment. Taken together, our findings elucidate a crucial immunomodulatory function for circulating ferritin that challenges the traditional view of this protein as a mere marker of body iron stores. Accordingly, these findings will stimulate investigations to the adaptive nature of this protein in diverse clinical settings.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ferritin
inflammatory response
sepsis
NF-B, cytokine
LPS
multi-organ injury
myeloid cells
Megjelenés:Frontiers in Immunology. - 10 (2019), p. 1-15. -
További szerzők:Black, Laurence M. McCullough, Kayla R. Hull, Travis D. Esman, Stephanie K. Boddu, Ravindra Varambally, Sooryanarayana Chandrashekar, Darshan S. Feng, Wenguang Arosio, Paolo Poli, Maura Balla József (1959-) (belgyógyász, nephrológus) Bolisetty, Subhashini
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