Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26773591
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Potentially diagnostic electron paramagnetic resonance spectra elucidate the
underlying mechanism of mitochondrial dysfunction in the deoxyguanosine kinase
deficient rat model of a genetic mitochondrial DNA depletion syndrome
#MMPMID26773591
Bennett B
; Helbling D
; Meng H
; Jarzembowski J
; Geurts AM
; Friederich MW
; Van Hove JLK
; Lawlor MW
; Dimmock DP
Free Radic Biol Med
2016[Mar]; 92
(?): 141-151
PMID26773591
show ga
A novel rat model for a well-characterized human mitochondrial disease,
mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase
(DGUOK) deficiency, is described. The rat model recapitulates the pathologic and
biochemical signatures of the human disease. The application of electron
paramagnetic (spin) resonance (EPR) spectroscopy to the identification and
characterization of respiratory chain abnormalities in the mitochondria from
freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR
is shown to be a sensitive technique for detecting mitochondrial functional
abnormalities in situ and, here, is particularly useful in characterizing the
redox state changes and oxidative stress that can result from depressed
expression and/or diminished specific activity of the distinct respiratory chain
complexes. As EPR requires no sample preparation or non-physiological reagents,
it provides information on the status of the mitochondrion as it was in the
functioning state. On its own, this information is of use in identifying
respiratory chain dysfunction; in conjunction with other techniques, the
information from EPR shows how the respiratory chain is affected at the molecular
level by the dysfunction. It is proposed that EPR has a role in mechanistic
pathophysiological studies of mitochondrial disease and could be used to study
the impact of new treatment modalities or as an additional diagnostic tool.
free
free
free
