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allied
academies
J u l y 2 3 - 2 4 , 2 0 1 8 | R o m e , I t a l y
TRADITIONAL
MEDICINE AND ACUPUNCTURE
8
th
International Conference on
Journal of General Internal Medicine
|
ISSN: 2591-7951
|
Volume 2
Traditional 2018
INHIBITION OF
MIR-128-3P
BY TONGXINLUO
PROTECTS HUMAN CARDIOMYOCYTES
FROM ISCHEMIA/REPERFUSION INJURY
VIA UPREGULATION OF P70S6K1/P-
P70S6K1
Guihao Chen, Ruijie Tang
and
Yuejin Yang
Peking Union Medical College, China
Aims:
Tongxinluo (TXL) is a multifunctional Traditional Chinese Medicine that
has been widely used to treat cardiovascular diseases. However, no studies
have explored whether TXL can protect human cardiomyocytes (HCMs) from
ischemia/reperfusion (I/R) injury. Reperfusion Injury Salvage Kinase (RISK)
pathway activation was previously demonstrated to protect the hearts against
I/R injury and it is generally activated via Akt or Erk 1/2, and their common
downstream protein, ribosomal protein S6 kinase (p70S6k). In addition, prior
studies proved that TXL treatment of cells promoted secretion of VEGF, which
could be stimulated by the increased phosphorylation of one p70S6k subtype,
p70S6k1. Consequently, we hypothesized TXL could protect HCMs from I/R
injury by activating p70S6k1 and investigated the underlying mechanism.
Methods & Results:
HCMs were exposed to hypoxia/reoxygenation (H/R),
with or without TXL pretreatment. H/R reduced mitochondrial membrane
potential, increased bax/bcl-2 ratios and cytochrome C levels and induced
HCM apoptosis. TXL preconditioning reversed these H/R-induced changes
in a dose-dependent manner and was most effective at 400 µg/mL. The anti-
apoptotic effect of TXL was abrogated by rapamycin, an inhibitor of p70S6k.
However, inhibitors of Erk1/2 (U0126) or Akt (LY294002) failed to inhibit
the protective effect of TXL. TXL increased p70S6k1 expression and, thus,
enhanced its phosphorylation. Furthermore, transfection of cardiomyocytes
with siRNA to p70S6k1 abolished TXL’s protective effects. Among the micro-
RNAs (
miR-145-5p
,
miR-128-3p
and miR-497-5p) previously reported to target
p70S6k1, TXL downregulated
miR-128-3p
in HCMs during H/R, but had no
effects on
miR-145-5p
and miR-497-5p. An in-vivo study confirmed the role
of the p70S6k1 pathway in the infarct-sparing effect of TXL, demonstrating
that TXL decreased
miR-128-3p
levels in the rat myocardium during I/R.
Transfection of HCMs with a hsa-
miR-128-3p
mimic eliminated the protective
effects of TXL.
Conclusions:
The
miR-128-3p
/p70S6k1 signaling pathway is involved in
protection by TXL against HCM apoptosis during H/R. Overexpression of
p70S6k1 is, therefore, a potential new strategy for alleviating myocardial
reperfusion injury.
Guihao Chen has completed his MD from Southern
Medical University and currently, he is pursuing his
PhD degree in Fuwai Hospital, Peking Union Medical
College. His research interests include acute myocar-
dial infarction complicated by cardiogenic shock, and
the protective effects of Chinese traditional medicine
in myocardial reperfusion injury. So far, he has pub-
lished more than 10 papers in reputed journals.
guihaochen123@126.comBIOGRAPHY
Guihao Chen et al., Arch Gen Intern Med 2018, Volume 2 | DOI: 10.4066/2591-7951-C1-002