| First Author | Nath KA | Year | 2000 |
| Journal | Am J Pathol | Volume | 156 |
| Issue | 5 | Pages | 1527-35 |
| PubMed ID | 10793064 | Mgi Jnum | J:108237 |
| Mgi Id | MGI:3623548 | Doi | 10.1016/S0002-9440(10)65024-9 |
| Citation | Nath KA, et al. (2000) The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. Am J Pathol 156(5):1527-35 |
| abstractText | Heme oxygenase (HO) is the rate limiting enzyme in the degradation of heme, and its isozyme, HO-1, may protect against tissue injury. One posited mechanism is the degradation of heme released from destabilized heme proteins. We demonstrate that HO-1 is a critical protectant against acute heme protein-induced toxicity in vivo. In the glycerol model of heme protein toxicity-one characterized by myolysis, hemolysis, and kidney damage-HO-1 is rapidly induced in the kidney of HO-1 +/+ mice as the latter sustain mild, reversible renal insufficiency without mortality. In stark contrast, after this insult, HO-1 -/- mice exhibit fulminant, irreversible renal failure and 100% mortality; HO-1 -/- mice do not express HO-1, and evince an eightfold increment in kidney heme content as compared to HO-1 +/+ mice. We also demonstrate directly the critical dependency on HO-1 in protecting against a specific heme protein, namely, hemoglobin: doses of hemoglobin which exert no nephrotoxicity or mortality in HO-1 +/+ mice, however, precipitate rapidly developing, acute renal failure and marked mortality in HO-1 -/- mice. We conclude that the induction of HO-1 is an indispensable response in protecting against acute heme protein toxicity in vivo. |
