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Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide

Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide

Chirag Vasavda, Ruchita Kothari, Adarsha P Malla, Robert Tokhunts, Anthony Lin, Ming Ji, Cristina Ricco, Risheng Xu, Harry G Saavedra, Juan I Sbodio, Adele M Snowman, Lauren Albacarys, Lynda Hester, Thomas W Sedlak, etc.

Cell Chem Biol. 2019 Oct 17;26(10):1450-1460.e7.

PMID: 31353321

Abstract:

Bilirubin is one of the most frequently measured metabolites in medicine, yet its physiologic roles remain unclear. Bilirubin can act as an antioxidant in vitro, but whether its redox activity is physiologically relevant is unclear because many other antioxidants are far more abundant in vivo. Here, we report that depleting endogenous bilirubin renders mice hypersensitive to oxidative stress. We find that mice lacking bilirubin are particularly vulnerable to superoxide (O2⋅-) over other tested reactive oxidants and electrophiles. Whereas major antioxidants such as glutathione and cysteine exhibit little to no reactivity toward O2⋅-, bilirubin readily scavenges O2⋅-. We find that bilirubin's redox activity is particularly important in the brain, where it prevents excitotoxicity and neuronal death by scavenging O2⋅- during NMDA neurotransmission. Bilirubin's unique redox activity toward O2⋅- may underlie a prominent physiologic role despite being significantly less abundant than other endogenous and exogenous antioxidants.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP635654	Bilirubin		635-65-4	Price

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