PubMed: 26974230

Title
Oxidized Ferric and Ferryl Forms of Hemoglobin Trigger Mitochondrial Dysfunction and Injury in Alveolar Type I Cells.
Journal
American journal of respiratory cell and molecular biology
Volume
55
Issue
None
Pages
288-98
Date
2016-08-01
Authors
Alayash AI | Chintagari NR | Jana S

Evidence 5373be067e

Moreover, mitochondrial translocation of HO-1 can also lead to localized CO production as a result of heme degradation, thus inhibiting electron flow though mitochondrial electron transport chain complex IV (44).

Evidence 9b0ac06335

Exposure to Hb and its oxidized products increases heme overload on the AT1 cells. Heme overload induces the expression of HO-1 and iron-sequestering proteins, such as ferritin.

Evidence 4ca6810aeb

We also found that HbFe21 and HbFe31 activate NF-kB and mitogen-activated protein kinase pathways, as shown by phosphorylation of NF-kB p65 subunit and p44/42, respectively (Figure E3) as noted previously (31).

Evidence 2946919820

Exposure to ferric Hb (HbFe31) induced a significant expression in HO-1 protein– (15.1761.04-fold) when compared with HbFe21 (9.3260.76-fold)- induced expression (Figure 2C).

Evidence d8b9802507

We found a significant enrichment of HO-1 in the mitochondrial, but not in the cytosolic fractions after exposure to HbFe21 and HbFe31 (Figures 3A and 3B).

Evidence f51f3408c2

Similarly, HbFe31 induced a significant expression H-ferritin protein (60.4062.76-fold) when compared with a 25.25 (61.91)-fold induction by HbFe21 (Figure 2D).

Evidence 66baa5e881

Exposure to HbFe21 and HbFe31 did not alter the expression of cytochrome c oxidase IV protein (Figure 3A).

Evidence 120bbbdeab

For example, HbFe41 (20 mM), but not HbFe31 or HbFe21, induced cytoskeletal reorganization, inflammation and disrupted barrier integrity in endothelial cells after 8 hours of incubation with the proteins.

Evidence 2786de1240

Exposure to HbFe41 caused a significant up-regulation of HO-1 within 12 hours when compared with HbFe21 and HbFe31 (Figures 4A and 4B).

Evidence 2c37cd1a40

We found significant enrichment of HO-1 in mitochondrial fraction after exposure to HbFe31 and HbFe41 (Figure 4C).

Evidence 798085f8cd

Exposure to HbFe41 resulted in a drop in hyperpolarized cell percentage over untreated control, thus indicating a significant mitochondrial depolarization or compromised mitochondrial respiration.

Evidence 726101899f

Subsequent RBC lysis leads to release of acellular Hb, which, in turn, damages the alveolar epithelial cells.

Evidence 0549bff6e5

We found that Hpx effectively attenuated HO-1 induction by all redox forms of Hb.

Evidence 6bd518c73b

Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B).

Evidence b09ced270a

Interestingly, Hp attenuated the HbFe21- and HbFe31-induced HO-1 expression in the mitochondria (Figures 3A and 3B).

Evidence 890faf51b8

However, hemin or LPS-induced mitochondrial accumulation of HO-1 was associated with decreased mitochondrial heme content and reduced expression of heme-sensitive subunit I of complex IV with loss of activity (33).

Evidence 7d8e76acce

A recent study indicated that expression of HO-1 targeted to mitochondria attenuated oxidative stress (43).

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