Role of Eicosanoids in Renal Disease
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Because of the beneficial effects of pharmacologic doses of PGEj on murine models of lupus nephritis, the effects of PGE1 on other models of immune complex disease were studied (Table 11). PGE1 treatment diminished proteinuria, glomerular damage, and immune complex deposition in mice treated with apoferritin (McLeish et al., 1980) and in rats treated with rabbit serum albumin (Nagamatsu et al., 1984). In the rat model, PGE1 treatment had the additional beneficial effect of decreasing an elevated plasma urea nitrogen. It was hypothesized that PGE1 treatment decreases circulating immune complexes by reducing specific antibody formation either with (McLeish et al., 1985) or without (Nagamatsu and Suzuki, 1986) a reduction in circulating leukocytes, or by enhancing the clearance of immune complexes (Nagamatsu et al., 1984). The effect of increasing endogenously produced PGs by altering the linoleic acid content of the diet was also investigated in immune complex nephritis. Mice maintained on a diet high in linoleic acid prior to the induction of immune complex nephritis with apoferritin had reduced proteinuria and renal histologic damage and showed no rise in serum creatinine (Kher et al., 1985).
The Use of Tracers in Transport Studies
Joan Gil in Models of Lung Disease, 2020
An anionic protein in its native form, horse spleen ferritin consists of a spherical apoferritin shell (~ 3 nm thick) with a diameter of — 13 nm (Fischbach et al., 1969) and a core of ferric hydroxyphosphate micelles that constitute up to 40% of its dry weight (Crichton, 1971). The prevalence of acidic residues impart to ferritin its pI of 4.5. By chemical modifications of protein functional groups (i.e., amino and carboxyl groups), anionic and cationic ferritin derivatives have been obtained (Danon et al., 1972; Rennke et al., 1975; Kanwar and Farquhar, 1979; Ghinea and Hasu, 1986). Ferritin (and its derivatives) has an Mr of ~ 960 kD, to which the apoferritin shell (composed of 24 subunits) contributes an Mr of ~ 445 kD (Panitz and Ghiglia, 1982). Ferritin is electron dense by virtue of its 5.5 nm iron core (Fig. 1a). The whole molecule (the iron core and the apoferritin shell) can become visible upon staining of sections with metallic bismuth, which binds to and stains the apoferritin shell, thus exposing the effective diameter of the molecule (Ainsworth and Karnovsky 1972). In addition to its value for its intrinsic electron opaqueness, ferritin was used successfully as tracer because of its relatively homogeneous size. When cadmium-free it is well tolerated by animals and may be coupled to active molecules to give conjugates that maintain appreciable biological activity (i.e., low-density lipoprotein-ferritin [Anderson et al., 1976], histamine-ferritin [Heltianu et al., 1983]).
The Hematologic System and its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
The life of a red blood cell is about 120 days, during which time some metabolic processes continue to occur. Some of the enzymes in the cytoplasm release energy to maintain cell integrity, but eventually the erythrocyte becomes fragile and breaks as it passes through a capillary. The fragments of the cell structure are engulfed by reticuloendothelial cells lining the capillaries of some organs, primarily the liver and spleen. These digest the fragments and release the dissolved components into the circulation. The hemoglobin molecules soon diffuse through the capillary walls and are engulfed by tissue reticuloendothelial cells. Digestion of hemoglobin releases the breakdown products iron and bilirubin. The iron combines with a globulin; to form transferrin, the form in which it is carried throughout the body for storage and reuse. In the liver, iron combines with apoferritin to form ferritin, conserving the iron for future use. The bilirubin is excreted through the liver into the bile.
Selective delivery of curcumin to breast cancer cells by self-targeting apoferritin nanocages with pH-responsive and low toxicity
Published in Drug Delivery, 2022
Peng Ji, Xianglong Wang, Jiabing Yin, Yi Mou, Haiqin Huang, Zhenkun Ren
Bio-nanomaterials have attracted more and more attention in the field of drug delivery due to their specific characteristics, such as precisely defined size, biocompatibility, and biodegradability (Ye et al., 2021b). Recombinant human heavy chain apoferritin (HFn), a hollow cage-like molecule composed of 24 protein subunits, has a molecular weight of 450 kDa, an inner diameter of 8 nm, and an outer diameter of 12 nm. Compared with other nanomaterials, HFn has the following unique characteristics (Pandolfi et al., 2017; He et al., 2019; Ji et al., 2019): first, HFn is a natural endogenous substance with good biocompatibility and low immunogenicity; second, HFn has a small and uniform particle size (<30 nm), enabling it to cross biological barriers and achieve deep penetration; third, it has pH-sensitive self-assembly properties. At strong acidic or alkaline pH, the shell of HFn is unfolded into a single subunit. When the pH is neutral, the shell is folded into the original quaternary structure; fourth, HFn has self-targeting properties. HFn is specifically recognized by transferrin receptor 1 (TfR1), which is overexpressed in several human breast cancers including 4T1 and MDA-MB-231, and promotes the intracellularization of these nanoparticles. These properties together make HFn an attractive new drug delivery carrier for cancer treatment.
Assessment of serum ferritin as a biomarker in COVID-19: bystander or participant? Insights by comparison with other infectious and non-infectious diseases
Published in Biomarkers, 2020
Kai Kappert, Amir Jahić, Rudolf Tauber
The pathophysiological background of hyperferritinemia in SARS-CoV-2 is not fully understood and remains hitherto elusive. Since hyperferritinemia in COVID-19 patients is most likely due to the observed cytokine storm and sHLH, forthcoming studies will have to address the question if macrophage activation and secretion via nonclassical pathways are responsible for the increased generation of serum ferritin (Cohen et al.2010). Moreover, it remains to be clarified if serum ferritin has protective effects by trapping of iron thus limiting the damage by free radicals generated in the presence of Fe(II) (Kernan and Carcillo 2017). Future studies may address the question if monitoring of total serum iron, serum ferritin and regulators of iron homeostasis such as hepcidin may give a hint if the elevation of serum ferritin may cause sequestration of iron into macrophages or hepatocytes. This could be of particular interest since cell culture experiments have shown that iron-loaded ferritin is more cytotoxic, while apoferritin appears to be protective (Kurz et al.2011).
MagA increases MRI sensitivity and attenuates peroxidation-based damage to the bone-marrow haematopoietic microenvironment caused by iron overload
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Yingying Shen, Cunjing Zheng, Yunpu Tan, Xinhua Jiang, Li Li
Based on the findings stated above, we undertook western blotting to further evaluate the iron metabolism of MagA-MSCs (Figure 8). Ferritin as an iron-storage protein is response to variations in iron content. We found that even at a low concentration of iron (20 μM), ferritin expression in control cells was upregulated, and was increased steadily in an iron-dependent manner. Increased expression of ferritin in MagA-MSCs was obviously weaker than that of control cells (Figure 8(d), #p < .01, n = 5), whereas a marked increase in expression of MagA protein was observed (Figure 8(c)). Nevertheless, the viability of MagA-MSCs was higher according to MTS assay, which inferred that MagA may help MSCs attenuate the injury caused by IO.
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