Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0022672 (
acute tubular necrosis
)
2,175
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Age sensitizes the kidney to heme protein-induced acute kidney injury. 2336 2
