WY 14,643 inhibits human aldose reductase activity.
Aldose reductase (AR) is implicated to play a critical role in diabetes and cardiovascular complications because of the reaction it catalyzes. Our data reveal that peroxisome proliferator WY 14,643, follows a pure non-competitive inhibition pattern in the aldehyde reduction activity as well as in the alcohol oxidation activity of AR. This finding communicates for the first time a novel feature of WY 14,643 in regulating AR activity. In addition, this observation indicates that AR, AR-like proteins and aldo-keto reductase (AKR) members may be involved in the WY 14,643 mechanism of action when it is administered as PPAR agonist.
Klemin
Sara
S
Division of Immunology, Beckman Research Institute and City of Hope National Medical Center, 1450 E. Duarte Road, Duarte, CA 91010, USA.
Calvo
Richard Y
RY
Bond
Stephanie
S
Dingess
Heather
H
Rajkumar
Balakrishnan
B
Perez
Rachel
R
Chow
Lucy
L
Balendiran
Ganesaratnam K
GK
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019905:Benzyl Alcohol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011743:Pyrimidines; C006253:pirinixic acid; D000449:Aldehyde Reductase; D019905:Benzyl Alcohol