# Memorial Sloan Kettering: DHRS7 enzyme controls inflammatory lipid 5-oxoETE in zebrafish and human cells

- Published: 2026-11-05 17:25 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: DHRS7 enzyme, 5-oxoETE, OXER1 receptor, NADP+/NADPH ratio, zebrafish inflammation model, NUDIX hydrolases, intestinal epithelium, redox signalling, Memorial Sloan Kettering
- URL: https://realtech.media/news/rt-e071e546c58412d5afe862ec_memorial_sloan_kettering/

**Researchers identified DHRS7 as the gene for an enzyme first observed in 1992 that makes and breaks down 5-oxoETE, a signal that both recruits immune cells and protects the gut epithelium.**

![Memorial Sloan Kettering: DHRS7 enzyme controls inflammatory lipid 5-oxoETE in zebrafish and human cells](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/bc915708d8534fe9.webp)
*ScienceDaily*

Researchers at Memorial Sloan Kettering Cancer Center (MSK) report in Nature that DHRS7, previously an orphan short-chain dehydrogenase–reductase, generates or consumes the pro-inflammatory lipid 5-oxoETE. The work was done in live zebrafish and human cells and published on October 7 [1].

## Identifying the missing gene

The enzyme was first observed in 1992 at McGill University, which described its ability to both produce and break down 5-oxoETE. The human gene behind it remained unknown for more than 30 years. Postdoctoral researcher Yanan Ma, building on earlier work by King Lam Hui, switched off candidate genes in cultured human cells and tracked the enzyme's activity. Disabling DHRS7 stopped it. The rodent version of the gene showed almost no activity. Mice also lack a known receptor for 5-oxoETE, so the full pathway cannot be studied in them, while it is intact in zebrafish.

## Redox-dependent signalling

According to the authors, the direction of the DHRS7 reaction depends on the cytoplasmic NADP+/NADPH ratio [1]. At wounds, where oxidative stress and NADP+ are high, DHRS7 produces 5-oxoETE, which alerts antimicrobial white blood cells through the G-protein-coupled receptor OXER1 [1]. In undamaged tissue, where NADP+ is low, DHRS7 removes 5-oxoETE and quenches unnecessary inflammation [1].

## Protective role in the intestine

A second project in the same laboratory, led by Miklos Lengyel, studied colitis in zebrafish. Removing hcar1-4, the zebrafish counterpart of human OXER1, was expected to reduce inflammation. Instead, the fish developed intestinal inflammation without any infection. Removing neutrophils did not eliminate it. The authors report that OXER1-deficient zebrafish show intestinal apoptosis, barrier disruption and microbial inflammation [1].

The mechanism involves NUDIX hydrolases. 5-oxoETE induces their expression, and they protect the cytoplasmic nucleotide pool from oxidation and prevent apoptosis in zebrafish and human intestinal cells [1]. The authors describe this as a conserved mode of redox sensing and signalling that goes beyond classic thiol oxidation and uses NADPH metabolism to coordinate both the antimicrobial and the pro-resilience functions of oxidative stress [1].

## Sources

1. [Nature](https://doi.org/10.1038/s41586-026-11121-2)
2. [ScienceDaily](https://www.sciencedaily.com/releases/2026/11/261101010554.htm)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-e071e546c58412d5afe862ec_memorial_sloan_kettering/