VTechWorks staff will be away for the winter holidays starting Tuesday, December 24, 2024, through Wednesday, January 1, 2025, and will not be replying to requests during this time. Thank you for your patience, and happy holidays!

Browsing by Author "Lianos, Elias A."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Data on characterization of metalloporphyrin-mediated HO-1 and DAF induction in rat glomeruli and podocytes
    Duann, P.; Lin, P.-H.; Lianos, Elias A. (Elsevier Inc., 2018-11-26)
    The data presented pertain to a research article titled “Heme Oxygenase 1 Up-Regulates Glomerular Decay Accelerating Factor Expression and Minimizes Complement Deposition and Injury” (Detsika et al., 2016). The present work provides additional data on induction and immunolocalization of heme oxygenase (HO)-1 (an antioxidant enzyme) and decay-accelerating factor (DAF) (a complement activation inhibitor) in isolated rat glomeruli and in glomerular epithelial cells (podocytes) in response to Iron Protoporphyrin IX (FePP, heme), and to non-iron protoporphyrins (PPs) with varying metal functionalities (ZnPP, SnPP), including a metal-devoid PP. Induction and immuno-localization of HO-1 and DAF in response to these metalloporphyrins (MP) were assessed using western blot analyses and confocal microscopy in isolated glomeruli and in cultured podocytes. These analyses identified podocytes as a major localization site of HO-1 and DAF induction in response to the aforementioned MPs. Effects of these MPs on a key glomerular structural protein, Nephrin, are also reported. The data identify MPs most and least capable of inducing DAF and reducing Nephrin expression and provide clues into expected outcomes of animal studies assessing MP efficacy in upregulating the cytoprotective proteins HO-1 and DAF.
  • Thumbnail Image
    Effect of Heme Oxygenase-1 Depletion on Complement Regulatory Proteins Expression in the Rat
    Detsika, Maria G.; Theochari, Eirini; Palamaris, Kostas; Gakiopoulou, Harikleia; Lianos, Elias A. (MDPI, 2022-12-27)
    Heme oxygenase has been implicated in the regulation of various immune responses including complement activation. Using a transgenic rat model of HO-1 depletion, the present study assessed the effect of HO-1 absence on the expression of complement regulatory proteins: decay accelerating factor (DAF), CR1-related gene/protein Y (Crry) and CD59, which act to attenuate complement activation. Protein expression was assessed by immunohistochemistry in kidney, liver, lung and spleen tissues. DAF protein was reduced in all tissues retrieved from rats lacking HO-1 (Ηmox1−/−) apart from spleen tissue sections. Crry protein was also reduced, but only in Ηmox1−/− kidney and liver tissue. C3b staining was augmented in the kidney and spleen from Ηmox1−/− rats, suggesting that the decrease of DAF and Crry was sufficient to increase C3b deposition. The observations support an important role of HO-1 as a regulator of the complement system.
  • Thumbnail Image
    Hemopexin Modulates Expression of Complement Regulatory Proteins in Rat Glomeruli
    Detsika, Maria G.; Lianos, Elias A. (MDPI, 2021-09-07)
    In systemic hemolysis and in hematuric forms of kidney injury, the major heme scavenging protein, hemopexin (HPX), becomes depleted, and the glomerular microvasculature (glomeruli) is exposed to high concentrations of unbound heme, which, in addition to causing oxidative injury, can activate complement cascades; thus, compounding extent of injury. It is unknown whether unbound heme can also activate specific complement regulatory proteins that could defend against complement-dependent injury. Isolated rat glomeruli were incubated in media supplemented with HPX-deficient (HPX−) or HPX-containing (HPX+) sera as a means of achieving different degrees of heme partitioning between incubation media and glomerular cells. Expression of heme oxygenase (HO)-1 and of the complement activation inhibitors, decay-accelerating factor (DAF), CD59, and complement receptor-related gene Y (Crry), was assessed by western blot analysis. Expression of HO-1 and of the GPI-anchored DAF and CD59 proteins increased in isolated glomeruli incubated with HPX− sera with no effect on Crry expression. Exogenous heme (hemin) did not further induce DAF but increased Crry expression. HPX modulates heme-mediated induction of complement activation controllers in glomeruli. This effect could be of translational relevance in glomerular injury associated with hematuria.
  • Thumbnail Image
    Metalloporphyrins as Tools for Deciphering the Role of Heme Oxygenase in Renal Immune Injury
    Lianos, Elias A.; Detsika, Maria G. (MDPI, 2023-04-06)
    Renal immune injury is a frequent cause of end-stage renal disease, and, despite the progress made in understanding underlying pathogenetic mechanisms, current treatments to preserve renal function continue to be based mainly on systemic immunosuppression. Small molecules, naturally occurring biologic agents, show considerable promise in acting as disease modifiers and may provide novel therapeutic leads. Certain naturally occurring or synthetic Metalloporphyrins (Mps) can act as disease modifiers by increasing heme oxygenase (HO) enzymatic activity and/or synthesis of the inducible HO isoform (HO-1). Depending on the metal moiety of the Mp employed, these effects may occur in tandem or can be discordant (increased HO-1 synthesis but inhibition of enzyme activity). This review discusses effects of Mps, with varying redox-active transitional metals and cyclic porphyrin cores, on mechanisms underlying pathogenesis and outcomes of renal immune injury.
  • Thumbnail Image
    Regulation of Complement Activation by Heme Oxygenase-1 (HO-1) in Kidney Injury
    Detsika, Maria G.; Lianos, Elias A. (2021-01)
    Heme oxygenase is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties. Its cytoprotective role is mainly attributed to its enzymatic activity, which involves the degradation of heme to biliverdin with simultaneous release of carbon monoxide (CO). Recent studies uncovered a new cytoprotective role for heme oxygenase-1 (HO-1) by identifying a regulatory role on the complement control protein decay-accelerating factor. This is a key complement regulatory protein preventing dysregulation or overactivation of complement cascades that can cause kidney injury. Cell-specific targeting of HO-1 induction may, therefore, be a novel approach to attenuate complement-dependent forms of kidney disease.