{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:17:56Z","timestamp":1789805876837,"version":"4.0.1"},"reference-count":218,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The heme molecule serves as an essential prosthetic group for oxygen transport and storage proteins, as well for cellular metabolic enzyme activities, including those involved in mitochondrial respiration, xenobiotic metabolism, and antioxidant responses. Dysfunction in both heme synthesis and degradation pathways can promote human disease. Heme is a pro-oxidant via iron catalysis that can induce cytotoxicity and injury to the vascular endothelium. Additionally, heme can modulate inflammatory and immune system functions. Thus, the synthesis, utilization and turnover of heme are by necessity tightly regulated. The microsomal heme oxygenase (HO) system degrades heme to carbon monoxide (CO), iron, and biliverdin-IX\u03b1, that latter which is converted to bilirubin-IX\u03b1 by biliverdin reductase. Heme degradation by heme oxygenase-1 (HO-1) is linked to cytoprotection via heme removal, as well as by activity-dependent end-product generation (i.e., bile pigments and CO), and other potential mechanisms. Therapeutic strategies targeting the heme\/HO-1 pathway, including therapeutic modulation of heme levels, elevation (or inhibition) of HO-1 protein and activity, and application of CO donor compounds or gas show potential in inflammatory conditions including sepsis and pulmonary diseases.<\/jats:p>","DOI":"10.3390\/ijms22115509","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T02:32:43Z","timestamp":1621823563000},"page":"5509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders"],"prefix":"10.3390","volume":"22","author":[{"given":"Stefan W.","family":"Ryter","sequence":"first","affiliation":[{"name":"Proterris, Inc., Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fphar.2017.00146","article-title":"Heme as a target for therapeutic interventions","volume":"8","author":"Immenschuh","year":"2017","journal-title":"Front. 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