Nrf2
Nrf2 is a transcription factor, a protein that switches genes on, that acts as the master switch for a cell's antioxidant defences, including the enzymes that make glutathione.
Also called NRF2, NFE2L2 (its gene), nuclear factor erythroid 2-related factor 2.
Nrf2 acts through a DNA sequence called the antioxidant response element and is one of the main regulators of the two glutathione-making enzymes, glutamate cysteine ligase and glutathione synthetase (Lu 2013).
In human cartilage cells, Nrf2 protein was about 40% lower in cells from older adults and about 50% lower in osteoarthritic cells than in younger cells (Taylor 2023). An oxidant challenge raised Nrf2 nearly fourfold in young cells but did not change it in old ones, and switching Nrf2 on with a drug increased aggrecan and type II collagen gene activity in osteoarthritic cells (Taylor 2023).
In mice, deleting the Nrf2 gene led to more severe osteoarthritis (Bolduc 2019).
Sources
- Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013.
- Taylor EL, Collins JA, Gopalakrishnan P et al. Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes. Osteoarthritis Cartilage 2023.
- Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med 2019.
Related terms
Read next
What happens to cartilage glutathione with age?
With age, cartilage cells tend to hold more of their glutathione in its used, oxidised form and cope worse with oxidative stress. In human cartilage cells, more than...
How do cartilage cells make glutathione?
Cartilage cells make glutathione in two enzyme steps. Glutamate cysteine ligase joins glutamate to cysteine, then glutathione synthetase adds glycine. How much a cell...
What does oxidative stress do to cartilage?
Oxidative stress is when a cell makes more reactive oxygen species than its antioxidants can clear. In cartilage it disrupts the cells' signalling and contributes to...