Cholinergic receptor-independent dysfunction of mitochondrial respiratory chain enzymes, reduced mitochondrial transmembrane potential and ATP depletion underlie necrotic cell death induced by the organophosphate poison mevinphos

Chan, Julie Y.H.; Chan, Samuel H.H.; Dai, Kuang-Yu; Cheng, Hung‐Liang; Chou, Jimmy Li-Jer; Chang, Alice Y.W.

doi:10.1016/j.neuropharm.2006.06.024

Cited by 44 publications

(34 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apoptosis may be caused by increased production of ROS and the translocation and inhibition of proteins involved in respiration such as cytochrome c 34. Mevinphos has been shown to disrupt oxidative phosphorylation by causing the dysfunction of complexes I through IV, which leads to cell death due to ATP depletion 35. Monocrotophos have also been shown to induce apoptosis in neurons and inhibit metabolism 34.…”

Section: Discussionmentioning

confidence: 99%

The association between ambient exposure to organophosphates and Parkinson's disease risk

Wang

Cockburn

et al. 2014

Occup Environ Med

View full text Add to dashboard Cite

Objectives There is a general consensus that pesticides are involved in the etiology of Parkinson’s disease (PD), although associations between specific pesticides and the risk of developing Parkinson’s disease have not been well studied. This study examines the risk of developing PD associated with specific organophosphate pesticides and their mechanisms of toxicity. Methods This case-control study uses a geographic information system (GIS)-based exposure assessment tool to estimate ambient exposure to 36 commonly used organophosphates (OPs) from 1974-1999. All selected OPs were analyzed individually and also in groups formed according to their presumed mechanisms of toxicity. Results The study included 357 incident PD cases and 752 population controls living in the Central Valley of California. Ambient exposure to each OP evaluated separately increased the risk of developing PD. However, most participants were exposed to combinations of OPs rather than a single pesticide. Risk estimates for OPs grouped according to different presumed functionalities and toxicities were similar and did not allow us to distinguish between them. However, we observed exposure-response patterns with exposure to an increasing number of OPs. Conclusions This study adds strong evidence that OPs are implicated in the etiology of idiopathic PD. However, studies of OPs at low doses reflective of real-world ambient exposure are needed to determine the mechanisms of neurotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

The association between ambient exposure to organophosphates and Parkinson's disease risk

Wang

Cockburn

et al. 2014

Occup Environ Med

View full text Add to dashboard Cite

show abstract

“…Complex I inhibitors such as rotenone and N-methylpyridinium ion generate free radicals in vivo (Ali et al 1994;Smith and Bennett 1997) and in vitro (Adams et al 1993;Wolvetang et al 1994) as does the complex IV inhibitor, azide (Partridge et al 1994;Smith and Bennett 1997). It has also been reported that mitochondrial complexes are inhibited in animals following OP administration (Li et al 2005;Chan et al 2006). MCP or DDVP induced oxidative stress might be responsible for decreased activities of mitochondrial complexes or vice versa.…”

Section: Discussionmentioning

confidence: 99%

“…MCP or DDVP induced oxidative stress might be responsible for decreased activities of mitochondrial complexes or vice versa. It has been reported that mitochondrial complexes are affected up to different degrees by different oxidizing species (Li et al 2005: Chan et al 2006). Cardiolipin, a vital phospholipid in mitochondria may be a likely target of peroxidative damage and contribute to impaired mitochondrial enzymes/function (Soussi et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial respiratory chain complexes have been reduced in rat rostral ventrolateral medulla after administration of mevinphos, an OP compound (Li et al 2005). In another study, Chan et al (2006) have reported decreased activities of complexes I-IV, reduction in mitochondrial transmembrane potential, depleted intracellular ATP content, and damaged cell membrane integrity following in vitro exposure of PC 12 cells to mevinphos.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

2009

View full text Add to dashboard Cite

Acute exposure to organophosphates induces a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy (OPIDN). The mechanism of OPIDN has not been fully understood as it does not involve cholinergic crisis. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. OPIDN was induced in rats by administering acute dose of monocrotophos (MCP, 20 mg/kg body weight, orally) or dichlorvos (DDVP, 200 mg/kg body weight, subcutaneously), 15-20 min after treatment with antidotes [atropine (20 mg/kg body weight) and 2-PAM (100 mg/kg body weight) intraperitoneally]. MDA levels were observed to be higher and thiol content was lower in mitochondria from brain regions of OP exposed animals. This was accompanied by decreased activities of the mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. In addition, mitochondrial functions assessed by MTT reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The spatial long-term memory evaluated using elevated plus-maze test was observed to be deficit in OPIDN. The results suggest impaired mitochondrial functions as a mechanism involved in the development of organophosphate induced delayed neuropathy.

show abstract

“…The immediate impetus for the present study is our recent demonstration (13) in PC12 cells, which share common biochemical and physiological characteristics with RVLM neurons, that Mev induces cholinergic receptorYindependent cell death. In addition, preliminary results from a parallel study revealed a surge in PKA activity in ventrolateral medulla during Mev intoxication.…”

Section: Introductionmentioning

confidence: 98%

Muscarinic Receptor-Independent Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase in Rostral Ventrolateral Medulla Underlies the Sympathoexcitatory Phase of Cardiovascular Responses During Mevinphos Intoxication in the Rat

Tsai

Chan

et al. 2007

Shock

View full text Add to dashboard Cite

As inhibitors of acetylcholinesterase, clinical presentations of poisoning from organophosphate compounds are generally believed to entail overstimulation by the accumulated acetylcholine on muscarinic receptors at peripheral and central synapses. That some patients still yielded to acute organophosphate poisoning despite repeated dosing of atropine suggests that cellular mechanisms that are independent of muscarinic receptor activation may also be engaged in organophosphate poisoning. The present study was undertaken to test the hypothesis that muscarinic receptor-independent activation of cyclic adenosine monophosphate-dependent protein kinase A (PKA) in rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts, is involved in the cardiovascular responses exhibited during organophosphate intoxication. In Sprague-Dawley rats, microinjection bilaterally of Mev (10 nmol) into the RVLM significantly augmented PKA activity in ventrolateral medulla that was not antagonized by coadministration of an equimolar concentration (1 nmol) of atropine or selective muscarinic receptor type M1 (pirenzepine), M2 (methoctramine), M3 (4-diphenyl-acetoxy-N-dimethylpiperidinium), or M4 (tropicamide) inhibitor. Comicroinjection of two selective PKA antagonists (100 pmol), N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide and (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolol[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-1][1,6]benzodiazocine-10-carboxylic acid, significantly blunted the initial sympathoexcitatory cardiovascular response and the accompanying augmentation of nitric oxide synthase (NOS I) expression in the ventrolateral medulla exhibited during Mev intoxication; the secondary sympathoinhibitory phase and associated elevation in NOS II expression were unaffected. We conclude that whereas a muscarinic receptor-independent augmentation of PKA activity in the ventrolateral medulla was manifested throughout acute Mev intoxication, this activation was preferentially involved in the sympathoexcitatory phase by an upregulation of NOS I expression.

show abstract

Cholinergic receptor-independent dysfunction of mitochondrial respiratory chain enzymes, reduced mitochondrial transmembrane potential and ATP depletion underlie necrotic cell death induced by the organophosphate poison mevinphos

Cited by 44 publications

References 47 publications

The association between ambient exposure to organophosphates and Parkinson's disease risk

The association between ambient exposure to organophosphates and Parkinson's disease risk

Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

Muscarinic Receptor-Independent Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase in Rostral Ventrolateral Medulla Underlies the Sympathoexcitatory Phase of Cardiovascular Responses During Mevinphos Intoxication in the Rat

Contact Info

Product

Resources

About