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Bisdemethoxycurcumin Protection of Cardiomyocyte Mainly Depends on Nrf2/HO‑1 Activation Mediated by the PI3K/AKT Pathway
journal contribution
posted on 2019-08-22, 19:33 authored by Xing Li, Cong Huo, Yuan Xiao, Rong Xu, Yan Liu, Xin Jia, Xiaoming WangBisdemethoxycurcumin
(BDMC) is one of three curcuminoids extracted
from turmeric. Unlike the dominant ingredient curcumin with some intensive
investigations, BDMC was recently reported to possess potent antitumor,
anti-inflammatory, antiatherosclerosis, antiobesity, and antiaging
effects. Considering its pharmacological effects in inflammation,
atherosclerosis, and obesity, this study was designed to examine if
BDMC displays cardioprotective properties. In this study, staurosporine
(STS) was used to establish the cardiomyocyte injury model. Our data
revealed that BDMC significantly inhibited myocardial apoptosis, improved
cell survival, reduced caspase-3 activity, and diminished reactive
oxygen species (ROS) production. BDMC enhanced phosphorylation of
protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)
and up-regulated the expression of HO-1. Inhibition of HO-1 activity
by using tin-protoporphyrin (SnPPIX) can restrain the antiapoptotic
effect of BDMC. Furthermore, translocation of Nrf2 from the cytoplasm
to the nucleus was ablated by LY294002, although only partially by
PD98059. Up-regulation of HO-1 was weakly suppressed by PD98059 but
strongly inhibited by LY294002. Unlike PD98059, LY294002 negated the
protective effect of BDMC. These findings indicated that BDMC possessed
favorable cardioprotection in a Nrf2/HO-1-dependent manner. Activation
of Nrf2/HO-1 mainly depended on PI3K/AKT but not MEK/ERK signaling.
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antiapoptotic effectBisdemethoxycurcumin ProtectionPD 98059LY 294002.protein kinase BROSreactive oxygen speciesantiaging effectsHO -1. InhibitionAKTPD 98059. Up-regulationBDMC displays cardioprotective propertiesextracellular signal-regulated kinaseMEKPI 3Kcaspase -3 activityERKNrf 2cardiomyocyte injury modelSTSingredient curcuminPI 3K Pathway Bisdemethoxycurcumincell survival
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