Abstract
Diabetic cardiomyopathy (DCM) is tightly linked to heart disorders and dysfunction or death of the cardiomyocytes including resident cardiac progenitor cells (CPCs) in diabetic patients. In order to restore loss of function of resident or transplanted CPCs, much research has focused on novel therapeutic strategies including the discovery of novel function-modulating factors such as reactive oxygen species (ROS) scavengers. Here, we developed and defined a novel antioxidant, MHY-1684, for enhancing the angiogenic potential of CPCs against ROS-related DCM. Short-term treatment with MHY-1684 restored ROS-induced CPC cell death. Importantly, MHY-1684 decreased hyperglycemia-induced mitochondrial ROS generation and attenuated hyperglycemia-induced mitochondrial fragmentation. We observed that the activation process of both Drp1 (phosphorylation at the site of Ser616) and Fis-1 is drastically attenuated when exposed to high concentrations of D-glucose with MHY-1684. Interestingly, phosphorylation of Drp1 at the site of Ser637, which is an inhibitory signal for mitochondrial fusion, is restored by MHY-1684 treatment, suggesting that this antioxidant may affect the activation and inhibition of mitochondrial dynamics-related signaling and mitochondrial function in response to ROS stress. In conclusion, our finding of the novel compound, MHY-1684, as an ROS scavenger, might provide an effective therapeutic strategy for CPC-based therapy against diabetic cardiomyopathy.
Highlights
Diabetes mellitus (DM), commonly called as diabetes, is a common public health problem worldwide
Regardless of the type, diabetes is categorized as a disease where blood glucose is elevated, and this eventually leads to hyperglycemia, which is a major cause of cardiovascular disease
To evaluate the impact of MHY-1684 on hCPC bioactivity, we investigated the effect of MHY-1684 on hCPC tubeforming ability and cell proliferation, including an investigation into the ERK1/2 and AKT pathway
Summary
Diabetes mellitus (DM), commonly called as diabetes, is a common public health problem worldwide. The most severe problems associated with diabetes are the various DMrelated complications such as cardiovascular diseases, renal diseases, neuropathy, and diabetic nephropathy. Oxidative Medicine and Cellular Longevity glucose level due to a malfunction in insulin secretion [1]. This malfunction is caused by the destruction of pancreatic beta cells in type I diabetes and insulin resistance in type II diabetes. Regardless of the type, diabetes is categorized as a disease where blood glucose is elevated, and this eventually leads to hyperglycemia, which is a major cause of cardiovascular disease. Hyperglycemia causes additional complications such as neuropathy, stroke, diabetic ketoacidosis, and a hyperosmolar hyperglycemic state [4, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
