Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia

Byung Hee Han, Ronald B. DeMattos, Laura L. Dugan, Jeong Sook Kim-Han, Robert P. Brendza, John D. Fryer, Malca Kierson, John Cirrito, Kevin Quick, Judith A K Harmony, Bruce J. Aronow, David M. Holtzman

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Clusterin, also known as apolipoprotein J, is a ubiquitously expressed molecule thought to influence a variety of processes including cell death. In the brain, it accumulates in dying neurons following seizures and hypoxic-ischemic (H-I) injury. Despite this, in vivo evidence that clusterin directly influences cell death is lacking. Following neonatal H-I brain injury in mice (a model of cerebral palsy), there was evidence of apoptotic changes (neuronal caspase-3 activation), as well as accumulation of clusterin in dying neurons. Clusterin-deficient mice had 50% less brain injury following neonatal H-I. Surprisingly, the absence of clusterin had no effect on caspase-3 activation, and clusterin accumulation and caspase-3 activation did not colocalize to the same cells. Studies with cultured cortical neurons demonstrated that exogenous purified astrocyte-secreted clusterin exacerbated oxygen/glucose-deprivation-induced necrotic death. These results indicate that clusterin may be a new therapeutic target to modulate non-caspase-dependent neuronal death following acute brain injury.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
JournalNature Medicine
Volume7
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Clusterin
Caspase 3
Brain Injuries
Brain
Ischemia
Neurons
Chemical activation
Cell death
Cell Death
Hypoxia
Cerebral Palsy
Astrocytes
Seizures
Oxygen
Glucose

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Han, B. H., DeMattos, R. B., Dugan, L. L., Kim-Han, J. S., Brendza, R. P., Fryer, J. D., ... Holtzman, D. M. (2001). Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. Nature Medicine, 7(3), 338-343. https://doi.org/10.1038/85487

Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. / Han, Byung Hee; DeMattos, Ronald B.; Dugan, Laura L.; Kim-Han, Jeong Sook; Brendza, Robert P.; Fryer, John D.; Kierson, Malca; Cirrito, John; Quick, Kevin; Harmony, Judith A K; Aronow, Bruce J.; Holtzman, David M.

In: Nature Medicine, Vol. 7, No. 3, 2001, p. 338-343.

Research output: Contribution to journalArticle

Han, BH, DeMattos, RB, Dugan, LL, Kim-Han, JS, Brendza, RP, Fryer, JD, Kierson, M, Cirrito, J, Quick, K, Harmony, JAK, Aronow, BJ & Holtzman, DM 2001, 'Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia', Nature Medicine, vol. 7, no. 3, pp. 338-343. https://doi.org/10.1038/85487
Han, Byung Hee ; DeMattos, Ronald B. ; Dugan, Laura L. ; Kim-Han, Jeong Sook ; Brendza, Robert P. ; Fryer, John D. ; Kierson, Malca ; Cirrito, John ; Quick, Kevin ; Harmony, Judith A K ; Aronow, Bruce J. ; Holtzman, David M. / Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. In: Nature Medicine. 2001 ; Vol. 7, No. 3. pp. 338-343.
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