D-Lactate altered mitochondrial energy production in rat brain and heart but not liver

Nutrition & Metabolism

Gordon A Zello¹  Brian Bandy¹  Katharina Lohmann²  Jane Alcorn¹  Fei Peng¹  Binbing Ling¹ 

[1] College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada;Large Animal Clinical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada

关键词: Heart;    Brain;    Rat;    Mitochondrial function;    D-Lactate;   

Others  :  820126
DOI  :  10.1186/1743-7075-9-6

 received in 2011-10-06, accepted in 2012-02-01,  发布年份 2012

【 摘 要 】

Background

Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart.

Methods

Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination.

Results

In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates.

Conclusions

DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.

【 授权许可】

   
2012 Ling et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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