Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Doxorubicin
(
DOXO
) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in
DOXO
-induced cardiotoxicity. In this study, we found that
DOXO
-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs.
DOXO
induced hCPC apoptosis with reduction of SMP30 (regucalcin) and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin) and
CaMKII
(Calmodulin kinase II). The results of an LC3 puncta assay further indicated that
DOXO
reduced autophagosome formation via accumulation of cytosolic Ca
2+
. Additionally,
DOXO
significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued
DOXO
-mediated autophagosome depletion in hCPCs with significant reduction of
DOXO
-mediated cytosolic Ca
2+
accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus,
DOXO
-mediated hCPC toxicity is linked to Ca
2+
-related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against
DOXO
-mediated hCPC toxicity.
...
PMID:Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca
2+
in Human Cardiac Progenitor Cells. 2773 42
