Open Collections

Mitochondrial complex I functionality and protein oxidative damage in lymphoblasts from lithium responsive patients with bipolar disorder, affected and unaffected relatives

University of British Columbia

Background: Evidence has demonstrated that mitochondria underline the neurobiology of bipolar disorder (BD). Investigating complex I functionality in transformed lymphoblasts from lithium responsive patients with BD, its relation with increased oxidative damage, and the response to stress induced by low glucose treatment, will aid in the search for peripheral biomarkers for this debilitating disorder. Objective: Confirm the alterations in complex I activity as well as levels of its subunit, NDUFS7, in addition to oxidative damage to mitochondrial proteins, by increased levels of protein carbonyls and 3-nitrotyrosine content, in lymphoblasts . The response to low glucose stress will be evaluated by measuring complex I activity, NDUFS7 levels, and protein oxidative damage. Design: Complex I activity was measured by spectrophotometry and tyrosine-nitration induced damage was assessed using a competitive enzyme immunoassay. Immunoblotting was used to measure NDUFS7 levels and protein carbonyl levels. All assays were carried out in cell pellet fractions, except for complex I activity which was carried out in mitochondrial fractions. Patients: We studied lymphoblasts from patients (14 with BD, and 14 relatives of BD patients affected with a psychiatric illness) and from non-psychiatric comparison controls (N=15) as well as 16 relatives of BD patients unaffected by a psychiatric illness. Results: Our results showed that levels of complex I activity in lymphoblasts differed significantly between the groups, with the lowest values for control subjects, and highest in unaffected and affected relatives, under normal glucose conditions. We did not find significant differences between the groups in NDUFS7, protein carbonyl, and 3-nitrotyrosine levels, nor did we find any correlation between complex I activity and NDUFS7, protein carbonyl, and 3-nitrotyrosine levels, for both treatment conditions (normal and low glucose). Conclusions: These findings suggest an up-regulation of peripheral complex I activity in patients with BD and their relatives, as a potential compensatory mechanism preventing protein oxidative damage induced by complex I dysfunctionality . Future studies, evaluating the potential role of lithium in peripheral cells targeting sites such as complex I, are necessary in order to gain insight into the mechanisms in which cells can prevent the oxidative damage characteristic of the disorder.

Text

2011-04-05

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/33274

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/