Disease relevance of Mtpn

• To investigate the physiological role of this protein, we examined the effect of V-1 overexpression on cell toxicity induced by nitric oxide (NO) used at low concentrations [1].
• To define the characteristics of each transcript and its pathophysiological significance, we examined transcripts of myotrophin in SHR heart during progression of hypertrophy [2].
• Our data strongly suggest that myotrophin appears to be a candidate gene for cardiac hypertrophy and heart failure [2].
• The gene encoding myotrophin has been cloned and expressed in E. coli [2].
• It is also suggested that V-1 expression is increased by hypertension in DS rat atrium [3].
• Myotrophin-induced myocyte growth and initiation of hypertrophy thus require nuclear co-translocation of myotrophin and p65, in a manner that depends crucially on the myotrophin hairpin loops [4].

Psychiatry related information on Mtpn

• V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats [5].

High impact information on Mtpn

• Increased protein kinase C activity in myotrophin-induced myocyte growth [6].
• The mechanism by which myotrophin stimulates protein synthesis and initiates myocardial hypertrophy is not known [6].
• Pretreatment of myocytes with staurosporine also reduced the myotrophin-induced mRNA levels of c-fos and beta-myosin heavy chain [6].
• To evaluate the subcellular events whose occurrence was due to myotrophin and translocation of PKC, we studied the effect of genistein, a tyrosine kinase inhibitor, on myotrophin-induced neonatal myocyte growth [6].
• Our data suggest that myotrophin exerts its action on protein synthesis, possibly through a tyrosine kinase-coupled pathway and translocation of PKC from the cytosol to the cell membrane [6].

Biological context of Mtpn

• Taken together, these results indicate that V1 protein plays an important role in protection against cell death induced by NO at low levels by promoting the synthesis of BH(4) [1].
• Moreover, these findings suggest the up-regulation of V1 expression as a possible therapeutic target for protection against the insult of NO-induced oxidative stress [1].
• Equilibrium folding and stability of myotrophin: a model ankyrin repeat protein [7].
• V-1 acts as a positive and coordinate regulator of gene expression of catecholamine biosynthetic enzymes in PC12D cells [8].
• Recently, myotrophin gene has been mapped and shown to be a novel gene localized in human chromosome 7q-33 [2].

Anatomical context of Mtpn

• Previously we reported that the synthesis of catecholamines, dopamine, and noradrenaline was enhanced by overexpression of V-1 protein, a neuronal protein active in the initial stage of development of the rat cerebellum, in the neuronal cell line PC12D, a model of dopamine cells (Yamakuni et al. [1998] J. Biol. Chem. 273:27051-27054) [1].
• Myotrophin has been shown to stimulate protein synthesis in myocytes and likely plays an important role in the initiation of cardiac hypertrophy, a major cause of mortality in humans [9].
• The present study was conducted to investigate the mechanism controlling expression of V-1 in the adrenal gland [8].
• Immunohistochemical analysis demonstrated that noradrenergic chromaffin cells more highly expressed V-1 than adrenergic chromaffin cells preferentially expressing the glucocorticoid receptor in rat adrenal glands [8].
• Down-regulation of V-1 also occurred during in vivo muscle differentiation from embryonic to postnatal stages, reaching an undetectable level in mature skeletal muscle [10].

Associations of Mtpn with chemical compounds

• Overexpression of V-1 prevents nitric oxide-induced cell death: involvement of enhanced tetrahydrobiopterin biosynthesis [1].
• High K(+)-induced dopamine secretion in V-1 overexpressing clones was shown to be markedly potentiated compared with control clones carried with a vector alone [11].
• Western blotting showed that in cultured bovine adrenal medullary cells, dexamethasone, a synthetic glucocorticoid, inhibited expression of V-1, and that this inhibition was prevented by RU-486, a glucocorticoid receptor antagonist [8].
• Genistein attenuated the [3H]leucine incorporation induced by myotrophin [6].
• The effect of myotrophin on the stimulation of PKC activity and [3H]leucine incorporation was abolished by pretreatment with either staurosporine or H-7, two selective, pharmacological PKC inhibitors [6].

Other interactions of Mtpn

• The increased BH(4) synthesis by V-1 overexpression was dose dependently inhibited by pretreatment with diaminohydroxypyrimidine (DAHP), an inhibitor of GTP-cyclohydrolase I, which is the rate-limiting enzyme for the biosynthesis of BH(4), concomitantly with the loss of protective effect afforded by V-1 overexpression [1].
• Our data showed that both cyclic stretch and exposure to high pressure caused significant increase in the transcript levels of myotrophin followed by expression of beta-myosin heavy chain and atrial natriuretic factor associated with an increase in myocardial protein synthesis [12].
• Neuronal activity and neurotrophic factors, known to be involved in granule cell differentiation, are major physiologic regulators of CREB function [13].
• The results demonstrate that a dramatic increase in the tonic NMDA receptor-channel activity occurs during the stages of granule cell differentiation, migration and synaptogenesis, which is driven by endogenous glutamate release and regulated by NMDA receptor density and local glutamate uptake [14].

Analytical, diagnostic and therapeutic context of Mtpn

• Northern blot analysis of myotrophin mRNA showed multiple transcripts [2].
• One of the proteins, V-1, was isolated using a liquid-chromatography system, and its amino acid sequence was determined by analysis of the purified protein [15].
• V-1 expression was shown to be increased in the atrial myocytes of these DS rats, but not in the sympathetic axons, when assayed by immunohistochemistry [3].
• Our successive studies were conducted to evaluate the pathophysiological significance of myotrophin; a solid-phase radioimmunoassay technique was developed for quantifying the protein in hypertrophied and normal hearts [16].
• As measured in the behaviorally tested rats, antisense treatment resulted in a reduced binding of radiolabeled AVP in the septum, but not in other limbic brain areas (receptor autoradiography), and an increased amount of V1 receptor mRNA (reverse transcriptase PCR), indicating translational arrest and ongoing transcriptional activity [5].

References