Dihydroxyacetone exposure alters NAD(P)H, induces mitochondrial stress and autophagy in HEK293T cells.

Dihydroxyacetone exposure alters NAD(P)H, induces mitochondrial stress and autophagy in HEK293T cells.

Publication date: Jul 22, 2019

Dihydroxyacetone phosphate (DHAP) is the endogenous by-product of fructose metabolism. Excess DHAP in cells can induce advanced glycation end products and oxidative stress. Dihydroxyacetone (DHA) is the triose precursor to DHAP. DHA is used as the active ingredient in sunless tanning products, including aerosolized spray tans, and is formed by the combustion of solvents found in electronic cigarettes. Human exposure to DHA has been increasing as the popularity of sunless tanning products and electronic cigarettes have grown. Topically applied DHA is absorbed through the viable layers of the skin and into the bloodstream. Exogenous exposure to DHA is cytotoxic in immortalized keratinocytes and melanoma cells with cell cycle arrest induced within 24 h and cell death occurring by apoptosis at consumer relevant concentrations of DHA within 72 h. Less is known about systemic exposures to DHA that occur following absorption through skin, and now through inhalation of the aerosolized DHA used in spray tanning. In the present study, HEK 293T cells were exposed to consumer-relevant concentrations of DHA to examine the cytotoxicity of systemic exposures. HEK 293T cells were sensitive to consumer-relevant doses of DHA with an IC50 value of 2.4 +/- 0.3 mM. However, cell cycle arrest did not begin until 48 h after DHA exposure. DHA exposed cells showed altered metabolic activity with decreased mitochondrial function and decreased lactate and ATP production observed within 24 h of exposure. Autofluorescent imaging and NAD+ sensors also revealed an imbalance in the redox cofactors NAD+/NADH within 24 h of exposure. Cell death occurred by autophagy indicated by increases in LC3B and SIRT1. Despite DHA’s ability to be converted to DHAP and integrated into metabolic pathways, the metabolic dysfunction and starvation responses observed in the HEK 293T cells indicate that DHA does not readily contribute to the energetic pool in these cells.

Smith, K.R., Hayat, F., Andrews, J.F., Migaud, M.E., and Gassman, N.R. Dihydroxyacetone exposure alters NAD(P)H, induces mitochondrial stress and autophagy in HEK293T cells. 23439. 2019 Chem Res Toxicol.

Concepts Keywords
Active Ingredient Glycation end products
Apoptosis Imaging
ATP Keratinocytes melanoma
Autophagy Ketones
Cofactors Chemistry
Combustion Organic compounds
Cytotoxic Branches of biology
Cytotoxicity Dihydroxyacetone
DHA Diols
Dihydroxyacetone Trioses
Dihydroxyacetone Phosphate Tanning
Electronic Cigarettes Organophosphates
Endogenous Sunless tanning
Fructose DHA
Glycation 293T
HEK Apoptosis
HEK293T Cells
IC50
Keratinocytes
Lactate
Melanoma
Metabolic Pathways
Metabolism
Mitochondrial
NAD+
NADH
NADPH
Oxidative Stress
Redox
SIRT1
Stress
Sunless Tanning
Tanning

Semantics

Type Source Name
disease MESH starvation
pathway BSID Metabolic pathways
gene UNIPROT SIRT1
gene UNIPROT MAP1LC3B
gene UNIPROT NDUFC2-KCTD14
drug DRUGBANK NADH
gene UNIPROT ATP8A2
drug DRUGBANK ATP
gene UNIPROT EPHA3
pathway BSID Apoptosis
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
drug DRUGBANK Doconexent
pathway BSID Oxidative Stress
disease MESH oxidative stress
pathway BSID Fructose metabolism
drug DRUGBANK Dihydroxyacetone phosphate
drug DRUGBANK Dihydroxyacetone

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