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Acrolein modifies protein functions and induces tissue damage at advanced age
Author(s) -
Uemura Takeshi,
Igarashi Kazuei
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.651.23
Subject(s) - acrolein , glyceraldehyde 3 phosphate dehydrogenase , glyceraldehyde , glutathione , biochemistry , chemistry , methylglyoxal , spermine , reactive oxygen species , in vivo , dehydrogenase , enzyme , biology , microbiology and biotechnology , catalysis
Acrolein (CH 2 =CHCHO) is a highly reactive unsaturated aldehyde generated mainly from oxidation of spermine, one of polyamines, in vivo . Acrolein causes strong oxidative stresses at sub microM concentration that is quite lower than reactive oxygen species (ROS). The activity of spermine oxidase, the enzyme involved in the generation of acrolein, is increased with age. Thus, acrolein plays important roles in tissue damage at advanced age such as brain stroke, dementia, renal failure and autoimmune diseases. As global society ages, it is required to prevent aging related diseases to maintain the quality of life (QOL) of the elderly. The objective of the presenting study is to identify the novel target of acrolein toxicity which can be a target for the prevention of age related disorders. We have analyzed proteins modified with acrolein in cells and identified GAPDH (glyceraldehyde‐3‐phosphate dehydrogenase), MMP‐9 (matrix metalloprotease 9), tubulin and GSTπ (glutathione S ‐transferase π). GAPDH was inactivated by acrolein modification that caused a decrease in cellular ATP content and induction of apoptosis through nuclear translocation. On the other hand, MMP‐9 was activated by acrolein to induce tissue damage in Sjogren's syndrome patients. Acrolein modification of tubulin inhibited polymerization of microtubules and disrupted cytoskeletal structures, then cell division and development of neuronal axons. GSTπ catalyzes conjugation of acrolein with glutathione in cells to neutralize it. GSTπ was modified and inactivated by acrolein to form polymer of proteins. In conclusion, we have found that through modification of GAPDH, MMP‐9, tubulin and GSTπ proteins, acrolein caused tissue damage in age related disorders. Acrolein scavengers can prevent the modification of proteins and further tissue damage. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .