hemeoxygenase-1

Overview

Hemeoxygenase-1 (HO-1) is a stress-inducible protein that functions as a key component of the cellular antioxidant and cytoprotective response. In biomedical research, HO-1 is commonly discussed as a downstream effector of nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent signaling and as part of broader antioxidant defense programs that also involve ferritin, catalase, superoxide dismutase 2 (SOD2), and GPX4. Its expression is often interpreted as a marker of oxidative stress adaptation, inflammation control, and ferroptosis-related regulation.

Recent studies in the provided literature contexts place HO-1 at the center of disease-associated redox biology, including metabolic dysfunction-associated fatty liver disease (MAFLD), colorectal cancer, photoaging, cerebral ischemia-reperfusion injury, gastric cancer, and UV-induced skin damage. Across these settings, HO-1 appears to be regulated by pathways such as Nrf2/HO-1-GPX4, SIRT1/FOXO3a, and other antioxidant networks, highlighting its role as both a biomarker and mechanistic mediator of cellular stress responses.

Focus of Latest Publications

Recent publications have examined HO-1 as a target or readout in several disease models linked to oxidative stress and ferroptosis. In MAFLD, serum HO-1 was significantly increased alongside ANGPTL7, TNF-α, IL-6, ACSL4, Keap-1, and ferritin, while IL-10, GPX4, and Nrf2 were decreased compared with controls. This pattern is consistent with altered ferroptosis-related and inflammatory signaling in metabolic liver disease, where HO-1 was evaluated together with ferritin and other Nrf2-associated antioxidant genes.

In colorectal cancer cells exposed to PhIP, HO-1 expression decreased, with concomitant upregulation of catalase and SOD2. This suggests that HO-1 was part of the oxidative stress response network affected by carcinogen-induced proliferative signaling. In a separate skin-aging study, SIRT1 was reported to protect human dermal fibroblasts from UVA-induced photoaging by suppressing oxidative stress and FOXO3a acetylation, thereby transcriptionally upregulating antioxidant defense genes including HO-1, SOD2, and CAT. Here, HO-1 was positioned as a downstream antioxidant effector within a SIRT1/FOXO3a-linked protective program.

HO-1 also featured prominently in ferroptosis-focused studies. In cerebral infarction-related microvascular injury, salvianolic acid B suppressed pro-ferroptotic mediators ACSL4 and TFR1 while enhancing Nrf2 nuclear translocation and upregulating downstream effectors HO-1 and GPX4, supporting a protective role for HO-1 in limiting ferroptosis and preserving microvascular integrity after ischemic injury. In contrast, a gastric cancer study reported that noni fruit juice induced ferroptosis in MKN45 and SNU-216 cells via the Nrf2/HO-1-GPX4 axis, indicating that HO-1 can also be involved in pro-ferroptotic therapeutic responses depending on context and upstream regulation.

In skin photoprotection research, Metabolites derived from dietary polyphenols increased hemeoxygenase-1 expression by 173% ± 26% in ex vivo human skin biopsies exposed to UV irradiation, while also reducing 4-hydroxynonenal protein adducts and mitigating elastin degradation. This supports HO-1 as a measurable marker of antioxidant defense in UV-damaged skin tissue. Collectively, these studies place HO-1 at the intersection of oxidative stress, inflammation, ferroptosis, and tissue protection, with recurring links to Nrf2, GPX4, ferritin, ACSL4, and related antioxidant pathways.

Key Publications

Jun Association of Serum Angiopoietin-Like Protein 7 With Ferroptosis-Related Proteins in Patients With Metabolic Dysfunction-Associated Fatty Liver Disease. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42247282): "Serum levels of ANGPTL7, TNF-α, IL-6, ACSL4, Keap-1, HO-1, and ferritin were significantly increased, while IL-10, GPX4, and Nrf2 levels were decreased in MAFLD patients when compared with the Con group (MAFLD vs. Con, all p < 0.001)."
Jun PAK2 Mediates PhIP-Induced Proliferative and Oxidative Stress Responses in Colorectal Cancer Cells. (Chemico-biological interactions, 2026, PMID 42276320): "as evidenced by decreased HO-1 expression and concomitant upregulation of catalase (CAT) and SOD2."
Jun SIRT1 protects against UVA-induced photoaging by suppressing oxidative stress and FOXO3a acetylation in human dermal fibroblasts. (Journal of photochemistry and photobiology. B, Biology, 2026, PMID 42033852): "enabling it to transcriptionally upregulate key antioxidant defense genes (SOD2, HO-1, CAT)."
Jun Nuclear Factor Erythroid 2-Related Factor 2-Dependent Ferroptosis Suppression by Salvianolic Acid B Preserves Microvascular Integrity and Reduces Risk Factors for Hemorrhagic Transformation After Cerebral Infarction. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42186809): "At the mechanistic level, Sal B suppressed pro-ferroptotic mediators ACSL4 and TFR1 while enhancing Nrf2 nuclear translocation and upregulating its downstream effectors HO-1 and GPX4."
May Noni (Morinda citrifolia L.) fruit juice induces ferroptosis in gastric cancer cells via the Nrf2/HO-1-GPX4 axis. (Food & function, 2026, PMID 42132559): "Mechanistically, noni juice regulates the GPX4/HO-1 axis to induce ferroptosis."
May Protecting Skin from UV Exposure with Dietary Polyphenols: Comparison of Phenolic Metabolites in an Ex Vivo Skin Explant Model. (Journal of agricultural and food chemistry, 2026, PMID 41830643): "Metabolites from the endogenous fermentation treatment provided the most comprehensive protection against UV-irradiation damage, reducing 4-hydroxynonenal protein adducts by 47.4% ± 9.9%, increasing hemeoxygenase-1 expression by 173% ± 26%, and mitigating elastin degradation by 82.8% ± 4.9%."