p(MGI:Hmox1)
Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
Heme induced the expression of Ho1 and Blvrb as well as Slc40a1, which encodes the mammalian iron exporter (Figure 5A), in agreement with previous reports (Delaby et al., 2008). PubMed:24630724
The Hmox1 (− /− ) MEF cells expressed no functional Hmox1 mRNA (Figure 1a) and as a result accumulated more cell-associated heme during extracellular exposure compared with wild-type cells (Figure 1b). PubMed:25301065
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. PubMed:26974230
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). PubMed:26974230
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). PubMed:26974230
In contrast, PPIX treatment of macrophages was capable of inducing Hmox-1 expression (Fig. 7C), indicating that PPIX was taken up by macrophages and catabolized (13). PubMed:29212341
Accordingly, higher levels of lipid peroxide-protein adducts were detected in heme-treated Hmox1 (− /−) than in Hmox1 (+/+) MEF cells when the cells were heme exposed in the presence of an alkyne-tagged analog of linoleic acid, which is an unsaturated, heme-reactive fatty acid (Supplementary Figure 3). PubMed:25301065
Exposure to HbFe41 caused a significant up-regulation of HO-1 within 12 hours when compared with HbFe21 and HbFe31 (Figures 4A and 4B). PubMed:26974230
We found significant enrichment of HO-1 in mitochondrial fraction after exposure to HbFe31 and HbFe41 (Figure 4C). PubMed:26974230
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). PubMed:26974230
In parallel to ferroportin, the expression of Hmox-1 was increased by heme-triggered ROS production and its induction was prevented by the combined treatment with NAC and heme (Fig. 8B). PubMed:29212341
Similarly, the induction of Hmox1 by heme was abolished by cotreatment with NAC and heme, supporting our in vitro findings (Fig. 8D). PubMed:29212341
We found that Hpx effectively attenuated HO-1 induction by all redox forms of Hb. PubMed:26974230
Consistently, HO-1 mRNA and protein levels were higher in hearts from Hx-/- mice than in controls (Figure 2B). Immunohistochemistry for HO-1 on heart sections indicated higher HO-1 expression in cardiomyocytes from Hx-/- mice than in wild-type animals (Figure 2B). PubMed:28400318
Mice that were resuscitated with SRBCs and albumin or SRBCs and hemopexin showed a marked increase in HO-1 expression when compared to mice resuscitated with FRBCs. PubMed:27515135
In contrast, albumin did not induce HO-1 or inhibit stasis and NF- κB. PubMed:29694434
Resuscitation with SRBCs and haptoglobin prevented the increase in SRBC-induced renal HO-1 expression (Figure 7F). PubMed:27515135
Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B). PubMed:26974230
Interestingly, Hp attenuated the HbFe21- and HbFe31-induced HO-1 expression in the mitochondria (Figures 3A and 3B). PubMed:26974230
Mice that were resuscitated with SRBCs and albumin or SRBCs and hemopexin showed a marked increase in HO-1 expression when compared to mice resuscitated with FRBCs. PubMed:27515135
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
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). PubMed:26974230
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
We have previously shown that induction of HO-1 expression or liver-directed HO-1 gene therapy inhibits stasis in sickle mice exposed to H/R [38, 45]. PubMed:29694434
For instance, Hmox−/− mice develops acute renal failure and marked mortality when submitted to rhabdomyolysis, a pathological condition that increases serum myoglobin which can be oxidized and release heme (Nath et al., 2000). PubMed:24904418
Furthermore, Hmox1−/− mice are susceptible to liver IR which is characterized by tissue damage in sites that are reperfused after ischemia injury and hemolysis (Devey et al., 2009). PubMed:24904418
During heme exposure the Hmox1 (−/ −) cells show a dose-dependent decrease in mitochondrial function as indicated by decreased cellular ATP (Figure 1c) and parallel induction of caspase 3/7 activity (Figure 1d) as well as nuclear condensation (Figure 1e) that occurred at heme concentrations exceeding 10 μM. PubMed:25301065
Moreover, HO-1 was highly expressed in the liver of CEP compared to WT mice (Figure 4E), confirming that residual heme uptake is rapidly degraded in the liver. PubMed:28143953
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637
Surprisingly, expression of neuronal activity marker cFos, astrocytic activity marker Gfap, and oxidative stress marker Hmox1 were reduced in the proaggregant Tau transgenic slices, whereas antiaggregant Tau transgenic slices were not different from littermate controls (Fig. 4A) PubMed:27671637
Mice lacking HO-1 (Hmox1−/−) are highly susceptible to pathologic conditions associated with increased serum heme concentration. PubMed:24904418
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
The Hmox1 (− /− ) MEF cells expressed no functional Hmox1 mRNA (Figure 1a) and as a result accumulated more cell-associated heme during extracellular exposure compared with wild-type cells (Figure 1b). PubMed:25301065
Macrophages are crucial for the removal of excess heme resulting from hemolysis via the uptake and degradation of heme by HO-1 (ref. 23), encoded by Hmox1. PubMed:27798618
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629
For instance, Hmox−/− mice develops acute renal failure and marked mortality when submitted to rhabdomyolysis, a pathological condition that increases serum myoglobin which can be oxidized and release heme (Nath et al., 2000). PubMed:24904418
Furthermore, Hmox1−/− mice are susceptible to liver IR which is characterized by tissue damage in sites that are reperfused after ischemia injury and hemolysis (Devey et al., 2009). PubMed:24904418
During heme exposure the Hmox1 (−/ −) cells show a dose-dependent decrease in mitochondrial function as indicated by decreased cellular ATP (Figure 1c) and parallel induction of caspase 3/7 activity (Figure 1d) as well as nuclear condensation (Figure 1e) that occurred at heme concentrations exceeding 10 μM. PubMed:25301065
We confirmed by selected reaction monitoring (SRM) mode mass spectrometry (Figure 3a) and western blot (Figures 3c and d), respectively, that heme increased Sqstm1, ubiquitin, and Hsp70, with a much stronger response in Hmox1 (−/− ) compared with Hmox1 (+/+) MEF cells. PubMed:25301065
We confirmed by selected reaction monitoring (SRM) mode mass spectrometry (Figure 3a) and western blot (Figures 3c and d), respectively, that heme increased Sqstm1, ubiquitin, and Hsp70, with a much stronger response in Hmox1 (−/− ) compared with Hmox1 (+/+) MEF cells. PubMed:25301065
We confirmed by selected reaction monitoring (SRM) mode mass spectrometry (Figure 3a) and western blot (Figures 3c and d), respectively, that heme increased Sqstm1, ubiquitin, and Hsp70, with a much stronger response in Hmox1 (−/− ) compared with Hmox1 (+/+) MEF cells. PubMed:25301065
Accordingly, higher levels of lipid peroxide-protein adducts were detected in heme-treated Hmox1 (− /−) than in Hmox1 (+/+) MEF cells when the cells were heme exposed in the presence of an alkyne-tagged analog of linoleic acid, which is an unsaturated, heme-reactive fatty acid (Supplementary Figure 3). PubMed:25301065
A recent study indicated that expression of HO-1 targeted to mitochondria attenuated oxidative stress (43). PubMed:26974230
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). PubMed:26974230
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). PubMed:26974230
Mice that were resuscitated with SRBCs and albumin or SRBCs and hemopexin showed a marked increase in HO-1 expression when compared to mice resuscitated with FRBCs. PubMed:27515135
Mice that were resuscitated with SRBCs and albumin or SRBCs and hemopexin showed a marked increase in HO-1 expression when compared to mice resuscitated with FRBCs. PubMed:27515135
Resuscitation with SRBCs and haptoglobin prevented the increase in SRBC-induced renal HO-1 expression (Figure 7F). PubMed:27515135
Moreover, HO-1 was highly expressed in the liver of CEP compared to WT mice (Figure 4E), confirming that residual heme uptake is rapidly degraded in the liver. PubMed:28143953
We have previously shown that induction of HO-1 expression or liver-directed HO-1 gene therapy inhibits stasis in sickle mice exposed to H/R [38, 45]. PubMed:29694434
BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.
If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.