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J Nutr Hum Health 2017 Volume 1 Issue 2
July 24-26, 2017 | Vancouver, Canada
International conference on
DIABETES, NUTRITION, METABOLISM & MEDICARE
Background:
Hyperglycemia results in the formation of
advanced glycation end products (AGEs), which can induce
reactive oxygen species (ROS) production leading to diabetic
cardiomyopathy. Our previous study showed that AGE
induced ROS-dependent apoptosis is mediated via the
protein kinase C (PKC) δ-enhanced mitochondrial damage
in cardiomyocytes. MicroRNA-210, a regulator of mitogen-
activated protein kinase-JNK (JNK), which is a downstream
of PKCδ, has been reported to play a role to mediate
mitochondrial function. Therefore, we hypothesized that
miR-210 mediates PKCδ-dependent upregulation of JNK to
cause cardiac mitochondrial damage and apoptosis following
AGE exposure.
Methods & Results:
Cardiac miR-210 and mitochondria
function were down regulated following AGE exposure.
Furthermore, JNK was up-regulated and involved in AGE-
induced mitochondrial damage. Interestingly, the result
of luciferase activity of the miR-210 mimic treatment was
significantly lower than control and was reversed following
the inhibitor treatment, indicating JNK is a target of miR210.
Moreover, JNK activation induced by AGEswas reduced by the
treatment of miR-210 mimic and reversed by the treatment
of miR-210 inhibitor, indicating the regulation function
of miR-210 for JNK activation following AGE exposure.
Additionally, the JNK-dependent mitochondrial dysfunction
was reversed following the treatment of miR210 mimic,
and miR210 inhibitor showed no effect on JNK-induced
mitochondrial dysfunction in AGE-exposed cardiomyocytes.
Conclusion:
PKCδ enhanced JNK-dependent mitochondrial
damage is mediated through the reduction of miR210 in
cardiomyocytes following AGE exposure. Additionally, the
JNK-dependent mitochondrial dysfunction was reversed
following the treatment of miR210 mimic, and miR210
inhibitor showed no effect on JNK-induced mitochondrial
dysfunction in AGE-exposed cardiomyocytes.
cyhuang@mail.cmu.edu.twMicroRNA-210 mediates PKCδ-dependent upregulation of JNK to cause cardiac mitochondrial damage
and apoptosis following advanced glycation end-products exposure
Wei-Wen Kuo
1
and
Chih-Yang Huang
1,2
1
China Medical University, Taiwan
2
Asia University, Taiwan