Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5 ′ -diphosphate bound conformation

Srinivasan, Chandra; Toon, Jason; Amari, Louis; Abukhdeir, Abde M.; Hamm, Heidi E.; Geraldes, Carlos F. G. C.; Ho, Yee-Kin; Freitas, Duarte Mota de

doi:10.1016/j.jinorgbio.2003.12.023

Cited by 22 publications

(20 citation statements)

References 40 publications

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“…Recently conducted nuclear magnetic resonance (NMR) studies with bovine IMPase [17] and binding site modeling studies [18] that calculated Gibbs free energy values for Mg 2+ and Li + binding sites on various IMPases and glycogen synthase kinase 3␤ (GSK-3␤) reveal that Li + can compete with Mg 2+ when certain conditions permit its physical accessibility to these proteins. Similar observations have been made by Srinivasan et al [19] with guaninenucleotide binding proteins (G-proteins). It should be noted that Li + competition with Mg 2+ is not thought to be universal with all proteins [18].…”

Section: Introductionsupporting

confidence: 84%

mRNA Transcript abundance during plant growth and the influence of Li+ exposure

et al. 2014

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Lithium (Li) toxicity in plants is, at a minimum, a function of Li(+) concentration, exposure time, species and growth conditions. Most plant studies with Li(+) focus on short-term acute exposures. This study examines short- and long-term effects of Li(+) exposure in Arabidopsis with Li(+) uptake studies and measured shoot mRNA transcript abundance levels in treated and control plants. Stress, pathogen-response and arabinogalactan protein genes were typically more up-regulated in older (chronic, low level) Li(+)-treatment plants and in the much younger plants from acute high-level exposures. The gene regulation behavior of high-level Li(+) resembled prior studies due to its influence on: inositol synthesis, 1-aminocyclopropane-1-carboxylate synthases and membrane ion transport. In contrast, chronically-exposed plants had gene regulation responses that were indicative of pathogen, cold, and heavy-metal stress, cell wall degradation, ethylene production, signal transduction, and calcium-release modulation. Acute Li(+) exposure phenocopies magnesium-deficiency symptoms and is associated with elevated expression of stress response genes that could lead to consumption of metabolic and transcriptional energy reserves and the dedication of more resources to cell development. In contrast, chronic Li(+) exposure increases expression signal transduction genes. The identification of new Li(+)-sensitive genes and a gene-based "response plan" for acute and chronic Li(+) exposure are delineated.

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Section: Introductionsupporting

confidence: 84%

mRNA Transcript abundance during plant growth and the influence of Li+ exposure

et al. 2014

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“…41–43 GTPases are a target of lithium, a drug frequently used to treat BD; and therefore, a role for G-proteins in disease processes of BD has long been hypothesized. 44–59 …”

Section: Discussionmentioning

confidence: 99%

Rare deleterious mutations are associated with disease in bipolar disorder families

et al. 2016

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Bipolar disorder (BD) is a common, complex, and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5 090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (p<0.05 after Bonferroni correction) and disease specificity was supported by the absence of the mutations in patients with SZ. In addition, we found rare, functional mutations in known causal genes for neuropsychiatric disorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.

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“…At therapeutic concentrations, lithium is known to inhibit a phosphodiesterase family of enzymes, which includes fructose 1,6-biphosphatase (FBPase), bisphosphate nucleotidase (BPNase), inositol monophosphatase (IMPase), and inositol polyphosphate 1-phosphatase (IPPase) all sharing a common sequence motif (York et al, 1995; Spiegelberg et al, 1999; Gould, 2006). Competition with magnesium for binding sites also modulates actions of lithium on G-protein-mediated cellular signaling transduction pathways (GTP binding and cyclic AMP production) through inhibition of adenylyl cyclase (Ebstein et al, 1976; Ebstein et al, 1978; Andersen and Geisler, 1984; Ebstein et al, 1987; Newman and Belmaker, 1987; Avissar et al, 1988; Mørk and Geisler, 1989; Minadeo et al, 2001; Srinivasan et al, 2004). Lithium selectively inhibits specific isoforms of adenylyl cyclase that are associated with antidepressant-like behaviors in animal models (Mann et al, 2008; Mann et al, 2009).…”

Section: Lithium and Magnesiummentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

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Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

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Competition between lithium and magnesium ions for the G-protein transducin in the guanosine 5 ′ -diphosphate bound conformation

Cited by 22 publications

References 40 publications

mRNA Transcript abundance during plant growth and the influence of Li+ exposure

mRNA Transcript abundance during plant growth and the influence of Li+ exposure

Rare deleterious mutations are associated with disease in bipolar disorder families

Molecular actions and clinical pharmacogenetics of lithium therapy

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