ArticleAmerican journal of physiology. Renal physiology2013
Age sensitizes the kidney to heme protein-induced acute kidney injury.
Article in American journal of physiology. Renal physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- The Aging Kidney and Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2026Review
- Review
- Is Hemopexin a Nephrotoxin or a Marker of Kidney Injury in Renal Ischemia-Reperfusion?Biomolecules · 2024Article
- Degree of PEGylatation ofACS applied bio materials · 2024Article
- Time- and Gender-Dependent Alterations in Mice during the Aging Process.International journal of molecular sciences · 2023Article
- Renal glomerular and tubular responses to glutaraldehyde- polymerized human hemoglobin.Frontiers in medicine · 2023Article
- Heme Proteins and Kidney Injury: Beyond Rhabdomyolysis.Kidney360 · 2022Review
- Interleukin-10 attenuates renal injury after myocardial infarction in diabetes.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2022Article
- In vivo growth of Staphylococcus lugdunensis is facilitated by the concerted function of heme and non-heme iron acquisition mechanisms.The Journal of biological chemistry · 2022Article
- Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney.Antioxidants (Basel, Switzerland) · 2022Article
- An ensemble prediction model for COVID-19 mortality risk.Biology methods & protocols · 2022Article
- Iron deficiency exacerbates cisplatin- or rhabdomyolysis-induced acute kidney injury through promoting iron-catalyzed oxidative damage.Free radical biology & medicine · 2021Article
- Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes.Frontiers in pharmacology · 2021Article
- New insights into the role of heme oxygenase-1 in acute kidney injury.Kidney research and clinical practice · 2020Review
- Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice.International journal of molecular sciences · 2020Article
- Resuscitation From Hemorrhagic Shock With Fresh and Stored Blood and Polymerized Hemoglobin.Shock (Augusta, Ga.) · 2020Article
- Characterization of Isolated Extracts fromMolecules (Basel, Switzerland) · 2020Article
- Mechanisms of haemolysis-induced kidney injury.Nature reviews. Nephrology · 2019Review
- Heme oxygenase-2 protects against ischemic acute kidney injury: influence of age and sex.American journal of physiology. Renal physiology · 2019Article
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Abstract
Age increases the risk for ischemic acute kidney injury (AKI). We questioned whether a similar age-dependent injury occurs following exposure to hemoglobin, a known nephrotoxin. Old mice (~16 mo old), but not young mice (~6 mo old), when administered hemoglobin, exhibited marked elevation in blood urea nitrogen (BUN) and serum creatinine, and acute tubular necrosis with prominent tubular cast formation. The aged kidney exhibited induction of heme oxygenase-1 (HO-1) and other genes/proteins that may protect against heme-mediated renal injury, including ferritin, ferroportin, haptoglobin, and hemopexin. Old mice did not evince induction of HO-2 mRNA by hemoglobin, whereas a modest induction of HO-2 mRNA was observed in young mice. To determine the functional significance of HO-2 in heme protein-induced AKI, we administered hemoglobin to relatively young HO-2(+/+) and HO-2(-/-) mice: HO-2(-/-) mice, compared with HO-2(+/+) mice, exhibited greater renal dysfunction and histologic injury when administered hemoglobin. In addition to failing to elicit a protective system such as HO-2 in response to hemoglobin, old mice exhibited an exaggerated maladaptive response typified by markedly greater induction of the nephrotoxic cytokine IL-6 (130-fold increase vs. 10-fold increase in mRNA in young mice). We conclude that aged mice, unlike relatively younger mice, are exquisitely sensitive to the nephrotoxicity of hemoglobin, an effect attended by a failure to induce HO-2 mRNA and a fulminant upregulation of IL-6. Age thus markedly augments the sensitivity of the kidney to heme proteins, and HO-2 confers resistance to such insults.
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