Protective role of microglial HO-1 blockade in aging: Implication of iron metabolism.

Redox Biology
Cristina Fernández-MendívilManuela G Lopez

Abstract

Heme oxygenase-1 (HO-1) is an inducible enzyme known for its anti-inflammatory, antioxidant and neuroprotective effects. However, increased expression of HO-1 during aging and age-related neurodegenerative diseases have been associated to neurotoxic ferric iron deposits. Being microglia responsible for the brain's innate immune response, the aim of this study was to understand the role of microglial HO-1 under inflammatory conditions in aged mice. For this purpose, aged wild type (WT) and LysMCreHmox1△△ (HMOX1M-KO) mice that lack HO-1 in microglial cells, were used. Aged WT mice showed higher basal expression levels of microglial HO-1 in the brain than adult mice. This increase was even higher when exposed to an inflammatory stimulus (LPS via i.p.) and was accompanied by alterations in different iron-related metabolism proteins, resulting in an increase of iron deposits, oxidative stress, ferroptosis and cognitive decline. Furthermore, microglia exhibited a primed phenotype and increased levels of inflammatory markers such as iNOS, p65, IL-1β, TNF-α, Caspase-1 and NLRP3. Interestingly, all these alterations were prevented in aged HMOX1M-KO and WT mice treated with the HO-1 inhibitor ZnPPIX. In order to determine the effects of ...Continue Reading

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Jan 6, 2021·International Journal of Molecular Sciences·Ayleen Fernández-FierroAlexis M Kalergis
May 1, 2021·International Journal of Molecular Sciences·Eleanor K Greenwood, David R Brown
Aug 3, 2021·American Journal of Physiology. Endocrinology and Metabolism·Qing Shen, Guo Zhang

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Methods Mentioned

BETA
Protein Assay
light microscopy

Software Mentioned

GraphPad Prism
Fiji

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