Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives

Westermann, Magdalena; Adomako-Bonsu, Amma G.; Thiele, Solveig; Çiçek, Serhat Sezai; Martin, H.; Maser, Edmund

doi:10.1016/j.cbi.2022.109823

Cited by 4 publications

(1 citation statement)

References 53 publications

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“…Usually, oxidation damages proteins through protein carbonylation, which occurs when carbonyl groups (aldehydes and ketones) are added to protein side chains (especially Pro, Arg, Lys, and Thr) [19], and protein carbonylation products are the best general indicator or molecular marker of oxidative stress [20,21]. In contrast, carbonyl reduction is catalysed by the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase (SDR) superfamilies [22][23][24]. Carbonyl reductases (CBRs) belong to the SDR family and NADPH is used as a cofactor for catalysing the two-electron reduction processes [25].…”

Section: Introductionmentioning

confidence: 99%

CBR1 decreases protein carbonyl levels via the ROS/Akt/CREB pathway to extend lifespan in the cotton bollworm, Helicoverpa armigera

Geng

Zhang

et al. 2022

The FEBS Journal

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Reactive oxygen species (ROS) are considered a major cause of ageing and ageing-related diseases through protein carbonylation. Little is known about the molecular mechanisms that confer protection against ROS. Here, we observed that, compared with nondiapause-destined pupae, high protein carbonyl levels are present in the brains of diapause-destined pupae, which is a 'non-ageing' phase in the moth Helicoverpa armigera. Protein carbonyl levels respond to ROS and decrease metabolic activity to induce diapause in order to extend lifespan. However, protein carbonylation in the brains of diapause-destined pupae still occurs at a physiological level compared to young adult brains. We find that ROS activate Akt, and Akt then phosphorylates the transcription factor CREB to facilitate its nuclear import. CREB binds to the promoter of carbonyl reductase 1 (CBR1) and regulates its expression. High CBR1 levels reduce protein carbonyl levels to maintain physiological levels. This is the first report showing that the moth brain can naturally control protein carbonyl levels through a distinct ROS-Akt-CREB-CBR1 pathway to extend lifespan.

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