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Anupam Agarwal - One of the best experts on this subject based on the ideXlab platform.

  • Heme Oxygenase 1 mitigates ferroptosis in renal proximal tubule cells
    American Journal of Physiology-renal Physiology, 2018
    Co-Authors: Oreoluwa O Adedoyin, Jeremie M. Lever, Anupam Agarwal, Ravindra Boddu, Amie M Traylor, Subhashini Bolisetty, James F George
    Abstract:

    Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme Oxygenase-1 (HO-1) is a cytoprotective enzyme in...

  • Heme Oxygenase 1 and the vascular bed from molecular mechanisms to therapeutic opportunities
    Antioxidants & Redox Signaling, 2008
    Co-Authors: Agnieszka Loboda, Anupam Agarwal, Alicja Jozkowicz, Agnieszka Jazwa, Anna Grochotprzeczek, A Rutkowski, Jaroslaw Cisowski, Jozef Dulak
    Abstract:

    Heme Oxygenase-1, an enzyme degrading Heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to Heme release. HO-1 protects endothelial cells from apoptosis, is involved in blood-vessel relaxation regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in blood-vessel formation by means of angiogenesis and vasculogenesis. The latter functions link HO-1 not only to cardiovascular ischemia but also to many other conditions that, like development, wound healing, or cancer, are dependent on neovascularization. The aim of this comprehensive review is to address the mechanisms of HO-1 regulation and function in cardiovascular physiology and pathology and to demonstrate some possible applications of the vast knowledge generated so far. Recent data provide powerful evidence for the involvement of HO-1 in the therapeutic effect of drugs used in cardiovascular diseases. No...

  • Heme Oxygenase 1 and carbon monoxide in vascular pathobiology focus on angiogenesis
    Circulation, 2008
    Co-Authors: Jozef Dulak, Jessy Deshane, Alicja Jozkowicz, Anupam Agarwal
    Abstract:

    Angiogenesis involves the formation of new blood vessels and is critical for fundamental events such as development and repair after injury. Perturbances in angiogenesis contribute to the pathogenesis of diverse clinical conditions including cancer, complications of diabetes mellitus, ischemia/reperfusion injury of the heart and other organs, and preeclampsia, as well as a number of inflammatory disorders. Recent work has identified Heme Oxygenase-1 and its gaseous product, carbon monoxide, to possess potent proangiogenic properties in addition to well-recognized antiinflammatory, antioxidant, and antiapoptotic effects. Angiogenic factors, such as vascular endothelial growth factor and stromal cell–derived factor-1, mediate their proangiogenic effects through induction of Heme Oxygenase-1, making it an attractive target for therapeutic intervention. This review will provide an overview of the role of Heme Oxygenase-1 and carbon monoxide in angiogenesis.

  • junb and jund regulate human Heme Oxygenase 1 gene expression in renal epithelial cells
    Journal of Biological Chemistry, 2007
    Co-Authors: Thomas D Hock, Marina Schorppkistner, Karen T Liby, Marcienne M Wright, Sean C Mcconnell, Thomas M Ryan, Anupam Agarwal
    Abstract:

    Abstract Heme Oxygenase-1 is a highly inducible gene, the product of which catalyzes breakdown of the prooxidant Heme. The purpose of this study was to investigate the regulation of the human Heme Oxygenase-1 gene in renal epithelial cells. DNase I hyper-sensitivity studies identified three distal sites (HS-2, -3, and -4) corresponding to approximately -4.0, -7.2, and -9.2 kb, respectively, of the Heme Oxygenase-1 promoter in addition to one proximal region, HS-1, which we have shown previously to be an E box. In vivo dimethyl sulfate footprinting of the HS-2 region revealed six individual protected guanines. Two mutations within HS-2 combined with a third mutation of the proximal E box abolished hemin- and cadmium-driven Heme Oxygenase-1 promoter activation, suggesting that these three sites synergized for maximal Heme Oxygenase-1 induction. Jun proteins bound to the antioxidant response element in the HS-2 region in vitro and associated with the Heme Oxygenase-1 promoter in vivo. JunB and JunD contribute opposing effects; JunB activated whereas JunD repressed Heme Oxygenase-1 expression in human renal epithelial cells, results that were corroborated in junB-/- and junD-/- cells. We propose that Heme Oxygenase-1 induction is controlled by a dynamic interplay of regulatory proteins, and we provide new insights into the molecular control of the human Heme Oxygenase-1 gene.

  • Heme Oxygenase 1 modulates early inflammatory responses evidence from the Heme Oxygenase 1 deficient mouse
    American Journal of Pathology, 2004
    Co-Authors: Matthias H Kapturczak, Clive Wasserfall, Todd M Brusko, Martha Campbellthompson, Tamir M Ellis, Mark A Atkinson, Anupam Agarwal
    Abstract:

    Induction of Heme Oxygenase-1 (HO-1) is protective in tissue injury in models of allograft rejection and vascular inflammation through either prevention of oxidative damage or via immunomodulatory effects. To examine the specific role of HO-1 in modulating the immune response, we examined the differences in immune phenotype between HO-1 knockout (HO-1−/−) and wild-type (HO-1+/+) mice. Consistent with previous findings, marked splenomegaly and fibrosis were observed in HO-1−/− mice. The lymph nodes of HO-1-deficient mice demonstrated a relative paucity of CD3- and B220-positive cells, but no such abnormalities were observed in the thymus. Flow cytometric analysis of isolated splenocytes demonstrated no differences in the proportions of T lymphocytes, B lymphocytes or monocytes/macrophages between the HO-1−/− and HO-1+/+ mice. Significantly higher baseline serum IgM levels were observed in HO-1−/− versus HO-1+/+ mice. Under mitogen stimulation with either lipopolysaccharide or anti-CD3/anti-CD28, HO-1−/− splenocytes secreted disproportionately higher levels of pro-inflammatory Th1 cytokines as compared to those from HO-1+/+ mice. These findings demonstrate significant differences in the immune phenotype between the HO-1−/− and the HO-1+/+ mice. The absence of HO-1 correlates with a Th1-weighted shift in cytokine responses suggesting a general pro-inflammatory tendency associated with HO-1 deficiency.

Alfred Kocher - One of the best experts on this subject based on the ideXlab platform.

Susumu Tonegawa - One of the best experts on this subject based on the ideXlab platform.

  • Heme Oxygenase 1 is required for mammalian iron reutilization
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.

  • Heme Oxygenase 1 is required for mammalian iron reutilization
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.

  • reduced stress defense in Heme Oxygenase 1 deficient cells
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    Stressed mammalian cells up-regulate Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1−/− embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1−/− mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.

  • reduced stress defense in Heme Oxygenase 1 deficient cells
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    Stressed mammalian cells up-regulate Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1−/− embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1−/− mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.

Kenneth D Poss - One of the best experts on this subject based on the ideXlab platform.

  • Heme Oxygenase 1 gene ablation or expression modulates cisplatin induced renal tubular apoptosis
    American Journal of Physiology-renal Physiology, 2000
    Co-Authors: Fumie Shiraishi, Kenneth D Poss, Lisa M Curtis, Leigh Truong, Gary A Visner, Kirsten Madsen, Harry S Nick, Anupam Agarwal
    Abstract:

    Heme Oxygenase-1 (HO-1) is a 32-kDa microsomal enzyme that catalyzes the conversion of Heme to biliverdin, releasing iron and carbon monoxide. Induction of HO-1 occurs as a protective response in c...

  • expression of Heme Oxygenase 1 can determine cardiac xenograft survival
    Nature Medicine, 1998
    Co-Authors: Miguel P Soares, Josef Anrather, Eva Csizmadia, Ko Takigami, Koichiro Sato, Shane T Grey, Robert B Colvin, Augustine M K Choi, Kenneth D Poss, Fritz H. Bach
    Abstract:

    The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts1,2,3,4,5,6. In concordant models, this type of rejection is prevented by brief complement inhibition by cobra venom factor (CVF) and sustained T-cell immunosuppression by cyclosporin A (CyA) (refs. 7,8,9,10 ). Mouse hearts that survive indefinitely in rats treated with CVF plus CyA express the anti-inflammatory gene Heme Oxygenase-1 (HO-1) in their endothelial cells and smooth muscle cells9,11,12,13,14. The anti-inflammatory properties of HO-1 are thought to rely on the ability of this enzyme to degrade Heme and generate bilirubin, free iron and carbon monoxide15. Bilirubin is a potent anti-oxidant13, free iron upregulates the transcription of the cytoprotective gene, ferritin16, and carbon monoxide is thought to be essential in regulating vascular relaxation in a manner similar to nitric oxide15. We show here that the expression of the HO-1 gene is functionally associated with xenograft survival, and that rapid expression of HO-1 in cardiac xenografts can be essential to ensure long-term xenograft survival.

  • Heme Oxygenase 1 is required for mammalian iron reutilization
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.

  • Heme Oxygenase 1 is required for mammalian iron reutilization
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    The majority of iron for essential mammalian biological activities such as erythropoiesis is thought to be reutilized from cellular hemoproteins. Here, we generated mice lacking functional Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron, to assess its participation in iron homeostasis. Hmox1-deficient adult mice developed an anemia associated with abnormally low serum iron levels, yet accumulated hepatic and renal iron that contributed to macromolecular oxidative damage, tissue injury, and chronic inflammation. Our results indicate that Hmox1 has an important recycling role by facilitating the release of iron from hepatic and renal cells, and describe a mouse model of human iron metabolic disorders.

  • reduced stress defense in Heme Oxygenase 1 deficient cells
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Kenneth D Poss, Susumu Tonegawa
    Abstract:

    Stressed mammalian cells up-regulate Heme Oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes Heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1−/− embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1−/− mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin. Our in vitro and in vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.

Martin Andreas - One of the best experts on this subject based on the ideXlab platform.