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Study · Ex vivo tissue · mouse · 2022

2 results

Oxidative degradation of dihydrofolate reductase increases CD38-mediated ferroptosis susceptibility.

Ma Y, Yi M, Wang W, Liu X, Wang Q, Liu C, Chen Y, Deng H

Cell death & disease9 Nov 2022Cited by 22 (Europe PMC)

PMID36351893 (opens in a new tab)PMCIDPMC9646779 (opens in a new tab)DOI10.1038/s41419-022-05383-7 (opens in a new tab)PepBankPUB-36351893
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Summary

High expression of CD38 in tissues is a characteristic of aging, resulting in a decline in nicotinamide adenine dinucleotide (NAD) and increasing cellular reactive oxygen species (ROS). However, whether CD38 increases susceptibility to ferroptosis remains largely unexplored. Our previous study showed that CD38 overexpression decreased dihydrofolate reductase (DHFR). In the present study, we confirmed that high expression of CD38 increased ROS levels and induced DHFR degradation, which was prevented by nicotinamide mononucleotide (NMN) replenishment. We further revealed that ROS-mediated sulfonation on Cys7 of DHFR induced its degradation via the autophagy and non-canonical proteasome pathways. Mutation of Cys7 to alanine abolished ROS-induced DHFR degradation. Moreover, oxidative degradation of DHFR was responsible for the increased ferroptosis susceptibility of cells in which CD38 was highly expressed. We also found that CD38 expression was higher in bone-marrow-derived macrophages (BMDMs) from aged mice than those from young mice, while the DHFR level was lower. Consequently, we demonstrated that BMDMs from aged mice were more susceptible to ferroptosis that can be reverted by NMN replenishment, suggesting that CD38 high expression rendered cells more susceptible to ferroptosis. Taken together, these results indicated that CD38-mediated NAD+ decline promoted DHFR oxidative degradation, thus resulting in increased cellular susceptibility to ferroptosis and suggesting that NMN replenishment may protect macrophages from ferroptosis in aged mice.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabEx vivo tissueMechanism

    In macrophages from aged mice, NMN replenishment reversed increased susceptibility to ferroptosis.

    In plain wordsIn lab tests on macrophages from aged mice, NMN reversed increased susceptibility to ferroptosis.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    DecreaseFerroptosis susceptibility
    Study

    mousen: not reported in source

    Bone-marrow-derived macrophages from aged mice
    Outcome group
    Cell viability and death · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Consequently, we demonstrated that BMDMs from aged mice were more susceptible to ferroptosis that can be reverted by NMN replenishment, suggesting that CD38 high expression rendered cells more susceptible to ferroptosis.
  2. 02LabIn vitro (cells)Mechanism

    In cells with high CD38 expression, NMN replenishment prevented DHFR degradation.

    In plain wordsIn cells with high CD38 expression, NMN prevented degradation of DHFR.

    Peptide
    NMN (nicotinamide mononucleotide)
    Outcome
    DecreaseDHFR degradation
    Study

    n: not reported in source

    Cells with high CD38 expression
    Outcome group
    Receptor activity and mechanism · Whole body
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the present study, we confirmed that high expression of CD38 increased ROS levels and induced DHFR degradation, which was prevented by nicotinamide mononucleotide (NMN) replenishment.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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