The Multifaceted Roles of DJ-1 as an Antioxidant.

The Multifaceted Roles of DJ-1 as an Antioxidant. Adv Exp Med Biol. 2017;1037:67-87 Authors: Raninga PV, Di Trapani G, Tonissen KF Abstract The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions. Other proteins regulated by DJ-1 include enzymes, chaperones, the 20S proteasome and transcription factors, including Nrf2. Once activated by oxidative stress, Nrf2 upregulates antioxidant gene expression including members of the thioredoxin and glutathione pathways, which in turn mediate an antioxidant protective function. Crosstalk between DJ-1 and both the thioredoxin and glutathione systems has also been identified. Thioredoxin reduces a cysteine residue on DJ-1 to modulate its activity, while glutaredoxin1 de-glutathionylates DJ-1, preventing degradation of DJ-1 and resulting in its accumulation. DJ-1 also regulates the activity of g...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research