Altered TRPC7 gene expression in bipolar-I disorder

Yoon, Il-Sang; Li, Peter P.; Siu, Kin Po; Kennedy, James L.; Macciardi, Fabìo; Cooke, R.G.; Parikh, Sagar V.; Warsh, Jerry J.

doi:10.1016/s0006-3223(01)01077-0

Cited by 67 publications

(47 citation statements)

References 29 publications

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“…The latter findings together with recent evidence of sexdependent abnormalities in variables such as basal and NaFstimulated cAMP production in BLCLs from BD-I patients 31 and in inositol monophosphatase 2 mRNA expression in both BLCLs and postmortem temporal cortex from BD-I patients 20 support the notion that sex-related differences in pathophysiology may occur in BD. That said, a caveat is the potential confounding effect of extraneous factors such as Li responsiveness or illness course and pattern specifiers.…”

Section: Discussionsupporting

confidence: 63%

“…6,9,20,37 Patients had a DSM-IV diagnosis of BD-I as established by the Structured Clinical Interview for DSM-IV (SCID), were physically healthy and had no recent (43 months) drug or alcohol abuse. 6 Healthy subjects had no past or current psychiatric illness as determined by SCID-I (nonpatient version) and were physically healthy as determined by systems review and physical examination.…”

Section: Subject B-lymphoblast Cell Linesmentioning

confidence: 99%

“…First, TG-induced Ca 2 þ responses, an index of SOCE, were blunted in platelets from BD patients compared with healthy subjects. 8 20 Third, chronic treatment of BLCLs from BD and healthy subjects with Li-attenuated LPA and TGinduced Ca 2 þ responses that likely involve SOCE and/or ROCE processes. 9 Recent research directed at elaborating the molecular components and/or mechanisms mediating SOCE and ROCE highlights the key role of several members of the TRP family of cation permeable channels in these processes in nonexcitable cells, such as lymphocytes and platelets.…”

Section: Introductionmentioning

confidence: 99%

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Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

et al. 2004

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Chronic lithium treatment of B-lymphoblast cell lines (BLCLs) from bipolar-I disorder (BD-I) patients and healthy subjects ex vivo attenuates agonist-and thapsigargin-stimulated intracellular calcium (Ca 2 þ ) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca 2 þ entry (SOCE) mechanisms, we determined whether chronic lithium treatment of BLCLs modified the expression of two members of the transient receptor potential channels (TRPC1 & 3), which participate in ROCE/SOCE. Chronic lithium treatment significantly reduced BLCL TRPC3 immunoreactivity (repeated-measures ANOVA, P ¼ 0.00005), with interaction effects of diagnosis (P ¼ 0.037) and sex (P ¼ 0.040). The lithium-induced decrease was greatest in BLCLs from female BD-I patients compared with those from healthy females (À27%) and with vehicle-treated BLCLs from female BD-I patients (À33%). However, lithium treatment did not affect TRPC1 and 3 mRNA levels, and TRPC1 immunoreactivity. Downregulation of TRPC3 may be an important mechanism by which lithium ameliorates pathophysiological Ca 2 þ disturbances as observed in BD.

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Section: Discussionsupporting

confidence: 63%

Section: Subject B-lymphoblast Cell Linesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

et al. 2004

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“…TRPM2 mRNA levels were significantly reduced in BLCLs from BD patients showing elevated BLCL [Ca 2 þ ] B and varied inversely with [Ca 2 þ ] B (Yoon et al, 2001b). Furthermore, in preliminary experiments, sustained elevation of BLCL [Ca 2 þ ] i by ionomycin treatment suppressed TRPM2 mRNA levels (Yoon, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…These include a marked blunting of Gprotein activated phosphoinositide (PI) hydrolysis (Jope et al, 1996) and altered mRNA expression levels of two candidate proteins, which may have important roles in Ca 2 þ homeostasis, inositol monophosphatase (IMPase) type II (Yoon et al, 2001a), and a transient receptor potential channel, TRPM2 (TRPC7 in earlier nomenclature) (Yoon et al, 2001b), a ligand-gated plasma membrane ion channel which also mediates Ca 2 þ entry into cells.…”

Section: Introductionmentioning

confidence: 99%

Chronic Lithium Treatment Attenuates Intracellular Calcium Mobilization

Wasserman

Corson

Sibony

et al. 2004

Neuropsychopharmacol

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Elevated basal intracellular calcium (Ca 2 þ ) levels ([Ca 2 þ ] B ) in B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients implicate altered Ca 2 þ homeostasis in this illness. Chronic lithium treatment affects key proteins modulating intracellular Ca 2 þ signaling. Thus, we sought to determine if chronic exposure to therapeutic lithium concentrations also modifies intracellular Ca 2 þ homeostasis in this surrogate cellular model of signal transduction disturbances in BD. BLCLs from BD-I (N ¼ 26) and healthy subjects (N ¼ 17) were regrown from frozen stock and incubated with 0.75 mM lithium or vehicle for 24 h (acute) or 7 days (chronic). [Ca 2 þ ] B , lysophosphatidic acid (LPA)-stimulated Ca 2 þ mobilization ([Ca 2 þ ] S ), and thapsigargin-induced store-operated Ca 2 þ entry (SOCE) were determined using ratiometric fluorometry with Fura-2. Compared with vehicle, chronic lithium exposure resulted in significantly higher [Ca 2 þ ] B (F ¼ 8.47; p ¼ 0.006) in BLCLs from BD-I and healthy subjects. However, peak LPA-stimulated [Ca 2 þ ] S and SOCE were significantly reduced (F ¼ 11.1, p ¼ 0.002 and F ¼ 8.36, p ¼ 0.007, respectively). Acute lithium exposure did not significantly affect measured parameters. In summary, the effect of chronic lithium to elevate [Ca 2 þ ] B in BLCLs while attenuating both receptor-stimulated and SOCE components of intracellular Ca 2 þ mobilization in BLCLs suggests that modulation of intracellular Ca 2 þ homeostasis may be important to the therapeutic action of lithium.

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Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder

Chun

Macciardi

et al. 2005

American J of Med Genetics Pt B

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Disturbed intracellular calcium (Ca(2+)) homeostasis has been implicated in bipolar disorder (BD). Reduced mRNA levels of the transient receptor potential Ca(2+) permeable channel melastatin type 2, TRPM2, in B lymphoblast cell lines (BLCL) from bipolar I disorder (BD-I) patients showing elevated basal intracellular Ca(2+) ([Ca(2+)](B)), an index of altered intracellular Ca(2+) homeostasis, along with its location within a putative BD susceptibility locus (21q22.3), implicates the involvement of this gene in the Ca(2+) abnormalities and the genetic diathesis to BD. We tested this hypothesis by examining the association of selected single nucleotide polymorphisms (SNPs) and their haplotypes, spanning the TRPM2 gene, with BD and BLCL [Ca(2+)](B), in a case control design. The 5' TaqMan SNP assay was used to detect selected SNPs. BLCL [Ca(2+)](B) was determined by ratiometric fluorometry. SNP rs1618355 in intron 18 was significantly associated with BD as a whole (P < 7.0 x 10(-5); odds ratio (OR) = 2.60), and when stratified into BD-I (P < 7.0 x 10(-5), OR = 2.48) and BD-II (P = 7.0 x 10(-5), OR = 2.88) subgroups. In addition, the alleles of the individual SNPs forming a seven marker at-risk haplotype were in excess in BD (12.0% in BD vs. 0.9% in controls; P = 2.3 x 10(-12)). A weak relationship was also detected between BLCL [Ca(2+)](B) and TRPM2 SNP rs1612472 in intron 19. These findings suggest genetic variants of the TRPM2 gene increase risk for BD and support the notion that TRPM2 may be involved in the pathophysiology of BD.

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Altered TRPC7 gene expression in bipolar-I disorder

Cited by 67 publications

References 29 publications

Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

Chronic Lithium Treatment Attenuates Intracellular Calcium Mobilization

Association of the putative susceptibility gene, transient receptor potential protein melastatin type 2, with bipolar disorder

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