Direct interactions of methamphetamine with the nucleus

Asanuma, Masato; Hayashi, Teruo; Ordonez, Sonia; Ogawa, Norio; Cadet, Jean Lud

doi:10.1016/s0169-328x(00)00128-5

Cited by 25 publications

(16 citation statements)

References 25 publications

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“…METH is a cationic lipophilic molecule that can diffuse into mitochondria and be retained by these organelles (Asanuma et al, 2000; Davidson et al, 2001). Accumulation of positively charged molecules in the mitochondria results in dissipation of the electrochemical gradient established by oxidative phosphorylation and inhibit ATP synthesis, causing energy deficiency and subsequent mitochondrial dysfunction (Wallace, 2005).…”

Section: Involvement Of Mitochondrial Pathways In Meth-induced Neurodmentioning

confidence: 99%

Methamphetamine toxicity and messengers of death

Krasnova¹,

Cadet²

2009

Brain Research Reviews

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529

534

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Methamphetamine (METH) is an illicit psychostimulant that is widely abused in the world. Several lines of evidence suggest that chronic METH abuse leads to neurodegenerative changes in the human brain. These include damage to dopamine and serotonin axons, loss of gray matter accompanied by hypertrophy of the white matter and microgliosis in different brain areas. In the present review, we summarize data on the animal models of METH neurotoxicity which include degeneration of monoaminergic terminals and neuronal apoptosis. In addition, we discuss molecular and cellular bases of METH-induced neuropathologies. The accumulated evidence indicates that multiple events, including oxidative stress, excitotoxicity, hyperthermia, neuroinflammatory responses, mitochondrial dysfunction, endoplasmic reticulum stress converge to mediate METH-induced terminal degeneration and neuronal apoptosis. When taken together, these findings suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity. Keywords methamphetamine; neurotoxicity; dopamine; oxidative stress; serotonin; cell death Epidemiology of Methamphetamine AbuseAbuse of the illegal psychostimulant, methamphetamine (METH), has become an international public health problem with an estimated 15-16 million users worldwide, a total which exceeds the number of people who abuse heroin and cocaine and makes METH the second most widely abused drug after cannabis (United Nations Office on Drugs and Crime, 2007). The inexpensive production of METH, its low cost, and long duration of action have made it a very desirable commodity. Indeed, METH is a popular drug of abuse in Australia (Australian Institure for Health and Welfare, 2005), Canada (Canadian Centre on Substance Abuse, 2005), Czech Republic and Slovakia (European Monitoring Center for Drugs and Drug Addiction, 2007). During the last decade, Southeast Asia and East Asia have become global hubs for METH production and trafficking, with a coincident epidemic of psychostimulant abuse in these regions (United Nations Office on Drugs and Crime, 2007). It is estimated that over half of the world's METH consumers reside in Southeast Asia and East Asia (United Nations Office on Drugs and Crime, 2007). Japan, in particular, has experienced several epidemics of crystal METH abuse, including a peak in 1999-2000. Since the late 1990s, METH use rose to epidemic Correspondence: Jean Lud Cadet M.D., Chief, Molecular Neuropsychiatry Reasearch Branch, Intramural Research Program, NIDA/NIH/ DHHS, 251 Bayview Boulevard, Baltimore, MD 21224, USA, jcadet@intra.nida.nih.gov, Tel: 443-740-2656, Fax: 443-740-2856. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before...

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Section: Involvement Of Mitochondrial Pathways In Meth-induced Neurodmentioning

confidence: 99%

Methamphetamine toxicity and messengers of death

Krasnova¹,

Cadet²

2009

Brain Research Reviews

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529

534

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“…A role for the ER in METH toxicity is supported by the fact that apoptotic doses of METH (Jayanthi et al, 2004) also influence the expression of proteins, such as caspase-12, GRP78/BiP (glucose-regulated protein/immuno-globulin heavy chain binding protein) and CHOP/GADD153 (C/EBP homology protein/ growth arrest and DNA damage 153) that participate in ER-induced apoptosis (Zinszner et al, 1998). The observed ER stress in METH-induced neurotoxicity might be secondary, in part, to direct effects of the psychostimulant (Asanuma et al, 2000), to METH-mediated oxidative stress (Cadet et al, 1994a;Cadet and Brannock, 1998;Jayanthi et al, 1998), and to shifts in BAX/Bcl-2 ratios induced by the drug .…”

Section: Involvement Of the Endoplasmic Reticulum (Er)-dependent Deatmentioning

confidence: 99%

Neurotoxicity of substituted amphetamines: Molecular and cellular mechanisms

et al. 2007

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The amphetamines, including amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are among abused drugs in the US and throughout the world. Their abuse is associated with severe neurologic and psychiatric adverse events including the development of psychotic states. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. The purpose of the present review is to summarize the toxic effects of AMPH, METH and MDMA. The paper also presents some of the factors that are thought to underlie this toxicity. These include oxidative stress, hyperthermia, excitotoxicity and various apoptotic pathways. Better understanding of the cellular and molecular mechanisms involved in their toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of amphetamine use disorders in humans.

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“…ER stress and calcium dysregulation have recently been implicated in METH-induced cellular demise by our recent observations that apoptotic doses of the drug can cause activation of calpain, a Ca 2ϩ -responsive cytosolic cysteine protease (172) that is an important early mediator of ER-dependent cell death (168). ER stress might be secondary to direct effects of METH, a very lipophilic drug (173); to METH-mediated oxidative stress (44,90,96); to shifts in the balance of BAX/Bcl-2 ratio induced by the drug (74); or to functional impairments of Na ϩ /H ϩ and Na ϩ /Ca 2ϩ antiporters (118). We found, in addition, that apoptotic doses of METH influence the pattern of expression of proteins that participate in ER-induced apoptosis and in the ER-mediated unfolded protein response (UPR) (174).…”

Section: Possible Involvement Of the Endoplasmic Reticulum (Er)-depenmentioning

confidence: 99%

Speed kills: cellular and molecular bases of methamphetamine‐induced nerve terminal degeneration and neuronal apoptosis

Cadet¹,

Jayanthi²,

Deng³

2003

FASEB j.

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259

246

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Methamphetamine (METH) is a drug of abuse that has long been known to damage monoaminergic systems in the mammalian brain. Recent reports have provided conclusive evidence that METH can cause neuropathological changes in the rodent brain via apoptotic mechanisms akin to those reported in various models of neuronal death. The purpose of this review is to provide an interim account for a role of oxygen-based radicals and the participation of transcription factors and the involvement of cell death genes in METH-induced neurodegeneration. We discuss data suggesting the participation of endoplasmic reticulum and mitochondria-mediated activation of caspase-dependent and -independent cascades in the manifestation of METH-induced apoptosis. Studies that use more comprehensive approaches to gene expression profiling should allow us to draw more instructive molecular portraits of the complex plastic and degenerative effects of this drug.

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Direct interactions of methamphetamine with the nucleus

Cited by 25 publications

References 25 publications

Methamphetamine toxicity and messengers of death

Methamphetamine toxicity and messengers of death

Neurotoxicity of substituted amphetamines: Molecular and cellular mechanisms

Speed kills: cellular and molecular bases of methamphetamine‐induced nerve terminal degeneration and neuronal apoptosis

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