Disease relevance of Dusp1

• Previously we found that rat mesangial cells express 3CH134/CL100 protein-tyrosine phosphatase (PTPase) in response to reactive oxygen intermediates (ROIs), and we now extend these studies to glomerulonephritis (GN), where ROI have been demonstrated to play a role [1].
• The influence of cell hydration on the heat shock response was investigated in H4IIE hepatoma cells at the levels of HSP70 expression, MAP kinase activation, induction of c-jun and the MAP kinase phosphatase MKP-1, heat resistance, and development of tolerance/sensitization to arsenite after a priming heat treatment [2].
• This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1 [3].
• Microarray, northern blot, and western blot analyses confirmed that MKP-1 mRNA and protein levels were up-regulated by hypoxia by approximately 8-fold [4].
• Here we provide evidence that the vascular response to acute hypertension also includes induction of MAP kinase phosphatase-1 (MKP-1), which has been shown to function in the dephosphorylation and inactivation of MAP kinases [5].

Psychiatry related information on Dusp1

• In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats [6].
• MKP-1 induced in rat brain after electroconvulsive shock is independent of regulation of 42- and 44-kDa MAPK activity [7].

High impact information on Dusp1

• Included among these were the genes for preprorelaxin, mitogen-activated protein kinase kinase 3, and the dual specificity protein phosphatase, rVH6 [8].
• The time course of the reduction in MKP-1 message correlated with increased tyrosine phosphorylation and elevated p44 MAP kinase enzymatic activity [9].
• We investigated the role of a dual-specificity tyrosine phosphatase, MAP kinase phosphatase-1 (MKP-1), in smooth muscle cell proliferation [9].
• After balloon injury of the rat carotid artery, expression of MKP-1 decreased greatly, whereas that of MAP kinases, especially p44 MAP kinase, increased [9].
• In rat arterial smooth muscle cells overexpressing MKP-1, growth was arrested in the G1 phase and entry into the S phase was blocked [9].

Chemical compound and disease context of Dusp1

• Cobalt and deferoxamine also increased MKP-1 mRNA levels, suggesting that hypoxia-inducible factor proteins may play a role in the regulation of MKP-1 by hypoxia [4].
• We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment [10].

Biological context of Dusp1

• Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway [11].
• Consistently, transfection with a wild-type MKP-1, but not its catalytically inactive mutant MKP-1CS, attenuated H(2)O(2)-induced apoptosis [11].
• These results indicate that rat CCH134/CL100 PTPase is actively induced in glomeruli as part of an acute immune injury at least in part related to oxidative stress [1].
• Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase-1, C/EBP-beta and ILAD-1, a novel gene with homology to arrestins [12].
• The rat homologue of 3CH134/CL100 was cloned from a rat macrophage cDNA library [1].

Anatomical context of Dusp1

• NEAP had a sequence characteristic of a dual-specificity phosphatase (DSP), and was preferentially expressed in neuroendocrine cells/tissues as well as in skeletal muscle and heart [13].
• In this study, we investigated signaling pathways involved in oxidative stress-induced MKP-1 expression and its role in apoptosis of rat mesangial cells [11].
• Re-exposure to the cue after 3 weeks of withdrawal reinstated heroin-seeking behaviour, which resulted in IEG expression of ania-3, MKP-1, c-fos and Nr4a3 in the medial prefrontal cortex (mPFC), and of ania-3 in the orbital frontal cortex (OFC) and nucleus accumbens core (NAC) [14].
• In anti-glomerular basement membrane (GBM) antibody (Ab) GN in rats, the 3CH134/CL100 PTPase mRNA was expressed in glomeruli as early as 30 minutes after anti-GBM Ab injection [1].
• Mitogen-activated protein kinase phosphatase-1 (MKP-1): >100-fold nocturnal and norepinephrine-induced changes in the rat pineal gland [15].

Associations of Dusp1 with chemical compounds

• TG selectively induced a sustained increase in MAPK phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by 2-APB, but not by nimodipine [16].
• Inhibition of MKP-1 by a protein tyrosine phosphatase inhibitor (vanadate) enhanced H(2)O(2)-triggered apoptosis [11].
• Selective inhibitors of individual MAP kinases or a dominant-negative mutant of c-jun significantly suppressed the expression of MKP-1 by H(2)O(2) [11].
• In this study, we investigated the mechanisms through which norepinephrine (NE) regulates MAPK phosphatase-1 (MKP-1) expression in rat pinealocytes [17].
• At the postreceptor level, treatment with dibutyryl cAMP caused parallel increases in MKP-1 mRNA and protein [17].

Physical interactions of Dusp1

• Site-directed mutagenesis of the reporter construct combined with band-shift and in vivo studies revealed that part of the constitutive activity of the MKP-1 promoter resides in two GC boxes bound by Sp1 and Sp3 transcription factors in the minimal promoter [18].

Enzymatic interactions of Dusp1

• Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual-specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids [19].

Regulatory relationships of Dusp1

• Overexpression of wild-type MKP-1 inhibited the phosphorylation of JNK and p38 in cardiomyocytes [20].
• Both actinomycin D and MKP-1 antisense oligonucleotides inhibited MKP-1 mRNA expression and caused prolonged activation of the p42 and p44 MAP kinases as measured by in-gel-kinase assays and Western blot [21].
• Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity [22].
• MAPK kinase inhibitor PD 98059 did abolish AA-stimulated activation of extracellular signal-regulated kinases but not MKP-1 induction [23].
• In addition, in CCL39 cells expressing an estradiol-inducible deltaRaf-1::ER chimera, activation of Raf alone is sufficient to induce MKP-1 and MKP-2 [24].

Other interactions of Dusp1

• These data elucidate, for the first time, that induction of MKP-1 by H(2)O(2) is mediated by the MAP kinase-AP-1 pathway and that the induced MKP-1 is involved in cellular defense against oxidative stress-induced apoptosis of mesangial cells [11].
• Immunofluorescent image analysis demonstrated trapping of phospho-p38 MAPK in the cytoplasm by MKP-1/CS/green fluorescent protein [25].
• ET-1-stimulated expression of COX-2 was increased in MKP-1/CS versus LacZ or green fluorescent protein-infected control cells [25].
• MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions [26].
• Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production [22].

Analytical, diagnostic and therapeutic context of Dusp1

• Northern and Western blot analyses showed that H(2)O(2) induced expression of MKP-1 mRNA and protein in a dose-dependent manner, without affecting the stability of the transcript [11].
• MKP-1 expression was high in arterial tissue by Northern analysis, and MKP-1 message was detected mainly in the arterial smooth muscle layer by in situ hybridization [9].
• In this study, we examined the regulation of mitogen-activated protein kinase phosphatase (MKP-1) expression by insulin in primary vascular smooth muscle cell cultures [22].
• Angiotensin II stimulated 3CH134 protein synthesis after 1 h as measured by immunoprecipitation of 3CH134 from [35S]methionine-labeled cells using affinity-purified antibodies [27].
• Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of MKP-1 mRNA followed by elevated MKP-1 protein expression in rat aorta [5].

References