Effect of Dopamine, Dimethoxyphenylethylamine, Papaverine, and Related Compounds on Mitochondrial Respiration and Complex I Activity

Morikawa, Nami; Nakagawa‐Hattori, Yuko; Mizuno, Yoshikuni

doi:10.1046/j.1471-4159.1996.66031174.x

Cited by 75 publications

(50 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated extracellular DA has been shown to create an oxidizing environment both in vitro and in vivo (62,63). This environment results in ROS damage and mitochondrial dysfunction analogous to our findings (64). Oxidative damage to lipids may result in increased lipid peroxides, including 4HNE.…”

Section: Discussionsupporting

confidence: 81%

Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice

Palacino

Sagi

Goldberg

et al. 2004

Journal of Biological Chemistry

904

661

View full text Add to dashboard Cite

Loss-of-function mutations in parkin are the predominant cause of familial Parkinson's disease. We previously reported that parkin؊/؊ mice exhibit nigrostriatal deficits in the absence of nigral degeneration. Parkin has been shown to function as an E3 ubiquitin ligase. Loss of parkin function, therefore, has been hypothesized to cause nigral degeneration via an aberrant accumulation of its substrates. Here we employed a proteomic approach to determine whether loss of parkin function results in alterations in abundance and/or modification of proteins in the ventral midbrain of parkin؊/؊ mice. Two-dimensional gel electrophoresis followed by mass spectrometry revealed decreased abundance of a number of proteins involved in mitochondrial function or oxidative stress. Consistent with reductions in several subunits of complexes I and IV, functional assays showed reductions in respiratory capacity of striatal mitochondria isolated from parkin؊/؊ mice. Electron microscopic analysis revealed no gross morphological abnormalities in striatal mitochondria of parkin؊/؊ mice. In addition, parkin؊/؊ mice showed a delayed rate of weight gain, suggesting broader metabolic abnormalities. Accompanying these deficits in mitochondrial function, parkin؊/؊ mice also exhibited decreased levels of proteins involved in protection from oxidative stress. Consistent with these findings, parkin؊/؊ mice showed decreased serum antioxidant capacity and increased protein and lipid peroxidation. The combination of proteomic, genetic, and physiological analyses reveal an essential role for parkin in the regulation of mitochondrial function and provide the first direct evidence of mitochondrial dysfunction and oxidative damage in the absence of nigral degeneration in a genetic mouse model of Parkinson's disease.

show abstract

Section: Discussionsupporting

confidence: 81%

Mitochondrial Dysfunction and Oxidative Damage in parkin-deficient Mice

Palacino

Sagi

Goldberg

et al. 2004

Journal of Biological Chemistry

904

661

View full text Add to dashboard Cite

show abstract

“…Papaverine blocks complex I and NADH-linked mitochondrial respiration, 11 depolarizes mitochondria directly, 12 and may inhibit specific dehydrogenase in the Krebs cycle. 13 An agent that blocks mitochondrial respiration would be expected to produce neurotoxicity similar to hypoglycemia consistent with what was seen histologically in case 5; it has also been reported to cause seizure.…”

Section: Discussionmentioning

confidence: 99%

Neurotoxicity of Intra-arterial Papaverine Preserved with Chlorobutanol Used for the Treatment of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Smith

Dowd

Johnston

et al. 2004

Stroke

104

View full text Add to dashboard Cite

Background and Purpose-Papaverine is used to vasodilate cerebral arteries undergoing vasospasm from subarachnoid hemorrhage. However, papaverine inhibits cellular respiration in vitro and could cause neurotoxicity in humans. Methods-We studied 5 consecutive patients with cerebral vasospasm who were treated with intra-arterial papaverine preserved with chlorobutanol and imaged with MRI fluid-attenuated inversion recovery and diffusion-weighted imaging after treatment. One patient had histological analysis of the brain at autopsy. Results-All 5 patients exhibited marked neurological decline immediately after treatment, and this was sustained through hospital discharge. In all cases, MRI images showed selective gray matter-only signal changes within the vascular territory treated with papaverine. Histological analysis of 1 case brought to autopsy showed selective injury to islands of neurons with relative sparing of white matter. Conclusions-Intra-arterial delivery of papaverine preserved with chlorobutanol into vasospastic anterior cerebral arteries may result in marked neurological deterioration with selective gray matter changes on MRI imaging. This effect is consistent with a permanent toxic effect to human brain. It is unclear whether this toxicity is caused by papaverine or chlorobutanol, and its use in the treatment of cerebral vasospasm should be reserved for cases without alternatives.

show abstract

“…As the neuronal degeneration in MPTP-induced parkinsonism is presumed to be caused by the inhibition of mitochondrial respiration by MPP + , the effects of THIQ-like alkaloids including THP and tetrahydropapaverine on the mitochondrial respiration were investigated using mouse brains [6,27,28]. Both compounds significantly inhibited state 3 and state 4 respiration and reduced the respiratory control ratio.…”

Section: Inhibition Of Mitochondrial Respirationmentioning

confidence: 99%