Document Detail


Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species.
MedLine Citation:
PMID:  18440987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Tianzheng Yu; Shey-Shing Sheu; James L Robotham; Yisang Yoon
Related Documents :
8737117 - Mechanisms of secondary brain injury.
11733517 - Inactivation of caspase-8 on mitochondria of bcl-xl-expressing mcf7-fas cells: role for...
9046537 - Spectrophotometric in vivo determination of local mitochondrial metabolism by use of a ...
2367527 - Stable expression of functional mitochondrial uncoupling protein in chinese hamster ova...
23928307 - Complement-mediated opsonization of invasive group a streptococcus pyogenes strain ap53...
18213527 - B-cell involvement in the pathogenesis of ra-is there a contribution of the sympathetic...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-04-25
Journal Detail:
Title:  Cardiovascular research     Volume:  79     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-02     Completed Date:  2008-09-23     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  341-51     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / cytology,  drug effects,  metabolism
Apoptosis / drug effects*
Cattle
Cells, Cultured
Disease Models, Animal
Dose-Response Relationship, Drug
Dynamin I / metabolism
Endothelium, Vascular / cytology,  drug effects,  metabolism
Glucose / pharmacology*
Hyperglycemia / metabolism
Mice
Mitochondria, Heart / metabolism*
Myocytes, Cardiac / cytology,  drug effects,  metabolism
Rats
Reactive Oxygen Species / metabolism*
Grant Support
ID/Acronym/Agency:
DK073858/DK/NIDDK NIH HHS; DK078618/DK/NIDDK NIH HHS; HL033333/HL/NHLBI NIH HHS; R01 DK078618/DK/NIDDK NIH HHS; R01 DK078618-01A1/DK/NIDDK NIH HHS; R01 HL033333/HL/NHLBI NIH HHS; R01 HL033333-19/HL/NHLBI NIH HHS; R21 DK073858/DK/NIDDK NIH HHS; R21 DK073858-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; EC 3.5.1.50/Dynamin I; IY9XDZ35W2/Glucose
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Overexpression of human truncated peroxisome proliferator-activated receptor alpha induces apoptosis...
Next Document:  Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism fo...