Abstract:
:Aldehydes are key intermediates in many cellular processes, from endogenous metabolic pathways like glycolysis to undesired exogenously induced processes such as lipid peroxidation and DNA interstrand cross-linking. Alkyl aldehydes are well documented to be cytotoxic, affecting the functions of DNA and protein, and their levels are tightly regulated by the oxidative enzyme ALDH2. Mutations in this enzyme are associated with cardiac damage, diseases such as Fanconi anemia (FA), and cancer. Many attempts have been made to identify and quantify the overall level of these alkyl aldehydes inside cells, yet there are few practical methods available to detect and monitor these volatile aldehydes in real time. Here, we describe a multicolor fluorogenic hydrazone transfer ("DarkZone") system to label alkyl aldehydes, yielding up to 30-fold light-up response in vitro. A cell-permeant DarkZone dye design was applied to detect small-molecule aldehydes in the cellular environment. The new dye design also enabled the monitoring of cellular acetaldehyde production from ethanol over time by flow cytometry, demonstrating the utility of the DarkZone dyes for measuring and imaging the aldehydic load related to human disease.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Yuen LH,Saxena NS,Park HS,Weinberg K,Kool ETdoi
10.1021/acschembio.6b00269subject
Has Abstractpub_date
2016-08-19 00:00:00pages
2312-9issue
8eissn
1554-8929issn
1554-8937journal_volume
11pub_type
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