Journal
CARDIOVASCULAR RESEARCH
Volume 79, Issue 2, Pages 341-351Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvn104
Keywords
mitochondria; mitochondrial fission; DLP1; Drp1; hyperglycaemia; apoptosis; reactive oxygen species
Categories
Funding
- NHLBI NIH HHS [R01 HL033333-19, HL033333, R01 HL033333] Funding Source: Medline
- NIDDK NIH HHS [R21 DK073858-02, R01 DK078618, R21 DK073858, DK073858, DK078618, R01 DK078618-01A1] Funding Source: Medline
Ask authors/readers for more resources
Aims One of the main causes of cardiovascular complications in diabetes is the hyperglycaemia-induced cell injury, and mitochondrial fission has been implicated in the apoptotic process. We investigated the role of mitochondrial fission in high glucose-induced cardiovascular cell injury. Methods and results We used several types of cultured mouse, rat, and bovine cells from the cardiovascular system, and evaluated mitochondrial morphology, reactive oxygen species (ROS) levels, and apoptotic parameters in sustained high glucose incubation. Adenoviral infection was used for the inhibition of the fission protein DLP1. We found that mitochondria were short and fragmented in cells incubated in sustained high glucose conditions. Under the same conditions, cellular ROS levels were high and cell death was increased. We demonstrated that the increased level of ROS causes mitochondrial permeability transition (MPT), phosphatidylserine exposure, cytochrome c release, and caspase activation in prolonged high glucose conditions. Importantly, maintaining tubular mitochondria by inhibiting mitochondrial fission in sustained high glucose conditions normalized cellular ROS levels and prevented the MPT and subsequent cell death. These results demonstrate that mitochondrial fragmentation is an upstream factor for ROS overproduction and cell death in prolonged high glucose conditions. Conclusion These findings indicate that the fission-mediated fragmentation of mitochondrial tubules is causally associated with enhanced production of mitochondrial ROS and cardiovascular cell injury in hyperglycaemic conditions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available