ArticleBiomolecules2015
Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress via Formed Bilirubin.
Article in Biomolecules, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Dissecting the Functional Interplay Between Heme Oxygenase LjHO1 and Leghemoglobins inBiology · 2025Article
- Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.World journal of gastroenterology · 2024Article
- Molecular mechanisms of bilirubin induced G1 cell cycle arrest and apoptosis in human breast cancer cell lines: involvement of the intrinsic pathway.Molecular biology reports · 2022Article
- Systemic Effects of mitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium.Antioxidants (Basel, Switzerland) · 2022Article
- Tissue Damage, Not Infection, Triggers Hepatic Unfolded Protein Response in an Experimental Rat Peritonitis Model.Frontiers in medicine · 2022Article
- Hemin-induced increase in saponin content contributes to the alleviation of osmotic and cold stress damage toJournal of Zhejiang University. Science. B · 2021Article
- Activation of artemisinin and heme degradation in Leishmania tarentolae promastigotes: A possible link.Biochemical pharmacology · 2020Article
- Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin.Antioxidants (Basel, Switzerland) · 2020Article
- Pioglitazone Attenuates Lipopolysaccharide-Induced Oxidative Stress, Dopaminergic Neuronal Loss and Neurobehavioral Impairment by Activating Nrf2/ARE/HO-1.Neurochemical research · 2019Article
- The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning.Antioxidants (Basel, Switzerland) · 2019Review
- Understanding the Role of the Antioxidant System and the Tetrapyrrole Cycle in Iron Deficiency Chlorosis.Plants (Basel, Switzerland) · 2019Article
- Cofilin signaling in hemin-induced microglial activation and inflammation.Journal of neuroimmunology · 2017Article
- Interaction between Mitochondrial Reactive Oxygen Species, Heme Oxygenase, and Nitric Oxide Synthase Stimulates Phagocytosis in Macrophages.Frontiers in medicine · 2017Article
- The Relationship between Serum Bilirubin and Elevated Fibrotic Indices among HBV Carriers: A Cross-Sectional Study of a Chinese Population.International journal of molecular sciences · 2016Article
- Glycolaldehyde induces endoplasmic reticulum stress and apoptosis in Schwann cells.Toxicology reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme oxygenase (HO), in conjunction with biliverdin reductase, degrades heme to carbon monoxide, ferrous iron and bilirubin (BR); the latter is a potent antioxidant. The induced isoform HO-1 has evoked intense research interest, especially because it manifests anti-inflammatory and anti-apoptotic effects relieving acute cell stress. The mechanisms by which HO mediates the described effects are not completely clear. However, the degradation of heme, a strong pro-oxidant, and the generation of BR are considered to play key roles. The aim of this study was to determine the effects of BR on vital functions of hepatocytes focusing on mitochondria and the endoplasmic reticulum (ER). The affinity of BR to proteins is a known challenge for its exact quantification. We consider two major consequences of this affinity, namely possible analytical errors in the determination of HO activity, and biological effects of BR due to direct interaction with protein function. In order to overcome analytical bias we applied a polynomial correction accounting for the loss of BR due to its adsorption to proteins. To identify potential intracellular targets of BR we used an in vitro approach involving hepatocytes and isolated mitochondria. After verification that the hepatocytes possess HO activity at a similar level as liver tissue by using our improved post-extraction spectroscopic assay, we elucidated the effects of increased HO activity and the formed BR on mitochondrial function and the ER stress response. Our data show that BR may compromise cellular metabolism and proliferation via induction of ER stress. ER and mitochondria respond differently to elevated levels of BR and HO-activity. Mitochondria are susceptible to hemin, but active HO protects them against hemin-induced toxicity. BR at slightly elevated levels induces a stress response at the ER, resulting in a decreased proliferative and metabolic activity of hepatocytes. However, the proteins that are targeted by BR still have to be identified.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.