Formaldehyde Causes Bone Marrow Failure Linked to Transcriptional Reprogramming or Metabolic Deficiency

Tan, Winnie; Deans, Andrew J.

doi:10.1016/j.molcel.2020.11.042

Cited by 5 publications

(5 citation statements)

References 12 publications

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“…Muscle atrophy and osteoporosis induced by the weightlessness of space are widely considered to be the main cause for motor deficits in astronauts 44 , 45 . Recent studies have found that excessive formaldehyde directly leads to muscle atrophy and osteoporosis in the mice with double-knockout of ADH5 and ALDH2 17 , 18 . The results of in vitro experiments showed that formaldehyde exposure not only inhibits the proliferation of muscular cells and osteoblast but also induces the death of these dells 46 , 47 .…”

Section: Discussionmentioning

confidence: 99%

“…Notably, exogenous formaldehyde or methanol (MeOH, a precursor of formaldehyde 14 ) poisoning also induced severe cerebellar ataxias in mice 15 and humans 16 . Recent studies revealed that the accumulated formaldehyde induces muscle atrophy and osteoporosis in the mice with double-knockout of alcohol dehydrogenase-5 (ADH5) and aldehyde dehydrogenase-2 (ALDH2) (two enzyme of clearance formaldehyde) 17 , 18 . Thus, an abnormal elevation in the levels of systemic formaldehyde may contribute to motor deficits of astronauts.…”

Section: Introductionmentioning

confidence: 99%

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Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

Yao

Bai

et al. 2021

Commun Biol

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During duration spaceflight, or after their return to earth, astronauts have often suffered from gait instability and cerebellar ataxia. Here, we use a mouse model of hindlimb unloading (HU) to explore a mechanism of how reduced hindlimb burden may contribute to motor deficits. The results showed that these mice which have experienced HU for 2 weeks exhibit a rapid accumulation of formaldehyde in the gastrocnemius muscle and fastigial nucleus of cerebellum. The activation of semicarbazide-sensitive amine oxidase and sarcosine dehydrogenase induced by HU-stress contributed to formaldehyde generation and loss of the abilities to maintain balance and coordinate motor activities. Further, knockout of formaldehyde dehydrogenase (FDH-/-) in mice caused formaldehyde accumulation in the muscle and cerebellum that was associated with motor deficits. Remarkably, formaldehyde injection into the gastrocnemius muscle led to gait instability; especially, microinfusion of formaldehyde into the fastigial nucleus directly induced the same symptoms as HU-induced acute ataxia. Hence, excessive formaldehyde damages motor functions of the muscle and cerebellum.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

Yao

Bai

et al. 2021

Commun Biol

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“…The hazards of formaldehyde mainly come from its effects on genetic material (Coggon et al 2003). Formaldehyde has high reactivity, and any formaldehyde that is not metabolised can cause DNA-adducts (including DNA-protein and DNA interstrand crosslinks) (Tan et al 2020). Formaldehyde reacts with common proteogenic amino acids and other nucleophilic amino acids at different rates through hydroxymethylation, cyclization, cross-linking or disproportionation, which have different stability and significant biochemical complexity.…”

Section: Health Hazards Mechanisms Of Formaldehyde Exposurementioning

confidence: 99%

“…ADH5 metabolizes exogenous formaldehyde into formate, thus preventing DPCs. When the gene of ADH5 is defective or mutant, exogenous formaldehyde can lead to bone marrow failure (Tan et al 2020). If this happens, Fanconi anemia complementation group D2 (FANCD2) protein repairs DNA lesions and prevents cell proliferation, thereby preventing leukaemia, liver dysfunction, and other diseases.…”

Section: Health Hazards Mechanisms Of Formaldehyde Exposurementioning

confidence: 99%

Health damage and repair mechanism related to formaldehyde released from wood-based panels

Gao

Yue

Yang

et al. 2023

BioRes

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Wood-based panels, which contain wood raw materials along with urea-formaldehyde (UF) or phenol-formaldehyde (PF) resins, can increase the indoor air concentration of formaldehyde. Formaldehyde can stimulate the upper respiratory mucosa and cross-linking reaction with cell proteins and DNA, and this can result in degeneration and necrosis of respiratory cells and damaged cell proliferation. Formaldehyde can induce health hazards such as nasal cancer, leukemia, and destruction of the reproductive system. Acetaldehyde dehydrogenase 5 (ADH5) in the body cooperates with Fanconi anaemia complementation group D2 (FANCD2) to quickly metabolize formaldehyde into formate and maintain the balance of endogenous formaldehyde. However, when both ADH5 and FANCD2 proteins have defects or mutations, damaged DNA repair failure and cell proliferation induce a variety of health diseases. The damage has been found in the upper respiratory area, not on distal body tissues such as liver, kidney, and bone marrow. Meanwhile epidemiological survey has not shown a positive correlation between formaldehyde and health hazards. It is recommended that the use of wood formaldehyde-based products should be reduced, and pathogenesis genes and damage repair mechanism should be studied systematically and deeply to develop gene drugs to remove excess formaldehyde and activate the damage gene repair mechanism in the future.

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“…(Pontel et al, 2015). In 2020, two papers showed that formaldehyde detoxification plays an essential role in hematopoietic differentiation and leukaemia (Dingler et al, 2020;Tan & Deans, 2020). Mice deficient in both formaldehydemetabolizing enzymes ADH5 and ALDH2 developed partial synthetic lethality and mortality shortly after birth.…”

Section: Adh2/gsnor1 Deficiency Renders Plants Susceptible To Dna Crosslinking Damagementioning

confidence: 99%

ADH2/GSNOR1 is a key player in limiting genotoxic damage mediated by formaldehyde and UV‐B in Arabidopsis

Wang

2021

Plant Cell & Environment

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Maintenance of genome stability is an essential requirement for all living organisms. Formaldehyde and UV-B irradiation cause DNA damage and affect genome stability, growth and development, but the interplay between these two genotoxic factors is poorly understood in plants. We show that Arabidopsis adh2/gsnor1 mutant, which lacks alcohol dehydrogenase 2/S-nitrosoglutathione reductase 1 (ADH2/GSNOR1), are hypersensitive to low fluence UV-B irradiation or UV-B irradiation-mimetic chemicals. Although the ADH2/GSNOR1 enzyme can act on different substrates, notably on S-hydroxymethylglutathione (HMG) and S-nitrosoglutathione (GSNO), our study provides several lines of evidence that the sensitivity of gsnor1 to UV-B is caused mainly by UV-B-induced formaldehyde accumulation rather than other factors such as alteration of the GSNO concentration. Our results demonstrate an interplay between formaldehyde and UV-B that exacerbates genome instability, leading to severe DNA damage and impaired growth and development in Arabidopsis, and show that ADH2/GSNOR1 is a key player in combating these effects.

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Formaldehyde Causes Bone Marrow Failure Linked to Transcriptional Reprogramming or Metabolic Deficiency

Cited by 5 publications

References 12 publications

Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading

Health damage and repair mechanism related to formaldehyde released from wood-based panels

ADH2/GSNOR1 is a key player in limiting genotoxic damage mediated by formaldehyde and UV‐B in Arabidopsis

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