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Mitochondrial NAD+-linked State 3 Respiration and Complex-I Activity are Compromised in the Cerebral Cortex of 3-Nitropropionic acid-induced rat model of Huntington’s disease

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Mitochondrial NAD+-linked State 3 Respiration and Complex-I Activity are Compromised in the Cerebral Cortex of 3-Nitropropionic acid-induced rat model of Huntington’s disease
 
Creator Pandey, Mritunjay
Varghese, Merina
Sindhu, Kizhake M
Sen, Sreetama
Navneet, A K
Mohanakumar , K P
Usha, Rajamma
 
Subject Cell Biology & Physiology
 
Description Mitochondrial complex-I dysfunction has been observed in patients of Huntington’s disease (HD). We assessed whether such a defect is present in the 3-nitropropionic acid (3-NP) model of HD. Rats treated with 3-NP (10–20 mg/kg i.p., for 4 days) exhibited weight loss, gait abnormalities, and striatal lesions with increased glial fibrillary acidic protein immunostaining on fifth and ninth days, while increase in striatal dopamine and loss of tyrosine hydroxylase immunoreactivity were observed on fifth day following treatment. We report for the first time a dose-dependent reduction in complex-I activity in the cerebral cortex when analyzed spectrophotometrically and by blue native-polyacrylamide gel electrophoresis following 3-NP treatment. The citrate synthase normalized activities of mitochondrial complex-I, -II, -(I + III) and -IV were decreased in the cortex of 3-NP treated rats. In addition, succinate driven State 3 respiration was also significantly inhibited in vivo and in the isolated mitochondria. These findings taken together with the observation of a significant decrease in vivo but not in vitro of State 3 respiration with NAD+-linked substrates, suggest complex-I dysfunction in addition to irreversible inhibition of complex-II and succinate dehydrogenase activity as a contributing factor in 3-NP induced cortico-striatal lesion.
 
Date 2008
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/230/1/JOURNAL_OF_NEUROCHEMISTRY%2C104(2)%2C420%2D434%2C2008_[155].pdf
Pandey, Mritunjay and Varghese, Merina and Sindhu, Kizhake M and Sen, Sreetama and Navneet, A K and Mohanakumar , K P and Usha, Rajamma (2008) Mitochondrial NAD+-linked State 3 Respiration and Complex-I Activity are Compromised in the Cerebral Cortex of 3-Nitropropionic acid-induced rat model of Huntington’s disease. Journal Of Neurochemistry, 104 (2). pp. 420-434.
 
Relation http://dx.doi.org/10.1111/j.1471-4159.2007.04996.x
http://www.eprints.iicb.res.in/230/