PubMed Health⌕ Search

Biomedical subjects

R Aikawa

Publications and source records attributed to R Aikawa.

26 records · Page 2Linked to original sources
PubMed1996

Protein kinase C, but not tyrosine kinases or Ras, plays a critical role in angiotensin II-induced activation of Raf-1 kinase and extracellular signal-regulated protein kinases in cardiac myocytes.

Angiotensin II (AngII) induces cardiac hypertrophy through activating a variety of protein kinases. In this study, to understand how cardiac hypertrophy develops, we examined AngII-evoked signal transduction pathways leading to the activation of extracellular signal-regulated protein kinases (ERKs), which are reportedly critical for the development of cardiac hypertrophy, in cultured cardiac myocytes isolated from neonatal rats. Inhibition of protein kinase C (PKC) with calphostin C or down-regulation of PKC by pretreatment with a phorbol ester for 24 h abolished AngII-induced activation of Raf-1 and ERKs, and addition of a phorbol ester conversely induced a marked increase in the activities of Raf-1 and ERKs. Pretreatment with two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and tyrphostin, did not attenuate AngII-induced activation of ERKs. In contrast, genistein strongly blocked insulin-induced ERK activation in cardiac myocytes. Although pretreatment with manumycin, a Ras farnesyltransferase inhibitor, or overexpression of a dominant-negative mutant of Ras inhibited insulin-induced ERK activation, neither affected AngII-induced activation of ERKs. Overexpression of a dominant-negative mutant of Raf-1 completely suppressed ERK2 activation by AngII, endothelin-1, and insulin. These results suggest that PKC and Raf-1, but not tyrosine kinases or Ras, are critical for AngII-induced activation of ERKs in cardiac myocytes.

Angiotensin II↗
PubMed1996

Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy.

We have recently shown that mechanical stress induces cardiomyocyte hypertrophy partly through the enhanced secretion of angiotensin II (ATII). Endothelin-1 (ET-1) has been reported to be a potent growth factor for a variety of cells, including cardiomyocytes. In this study, we examined the role of ET-1 in mechanical stress-induced cardiac hypertrophy by using cultured cardiomyocytes of neonatal rats. ET-1 (10(-8) approximately 10(-7) M) maximally induced the activation of both Raf-1 kinase and mitogen-activated protein (MAP) kinases at 4 and 8 min, respectively, followed by an increase in protein synthesis at 24 h. All of these hypertrophic responses were completely blocked by pretreatment with BQ123, an antagonist selective for the ET-1 type A receptor subtype, but not by BQ788, an ET-1 type B receptor-specific antagonist. BQ123 also suppressed stretch-induced activation of MAP kinases and an increase in phenylalanine uptake by approximately 60 and 50%, respectively, but BQ788 did not. ET-1 was constitutively secreted from cultured cardiomyocytes, and a significant increase in ET-1 concentration was observed in the culture medium of cardiomyocytes after stretching for 10 min. After 24 h, an approximately 3-fold increase in ET-1 concentration was observed in the conditioned medium of stretched cardiomyocytes compared with that of unstretched cardiomyocytes. ET-1 mRNA levels were also increased at 30 min after stretching. Moreover, ET-1 and ATII synergistically activated Raf-1 kinase and MAP kinases in cultured cardiomyocytes. In conclusion, mechanical stretching stimulates secretion and production of ET-1 in cultured cardiomyocytes, and vasoconstrictive peptides such as ATII and ET-1 may play an important role in mechanical stress-induced cardiac hypertrophy.

Animals↗
PubMed1996

Molecular cloning and characterization of human cardiac homeobox gene CSX1.

Accumulating evidence has suggested that homeo-domain-containing proteins play critical roles in regulating the tissue-specific gene expression essential for tissue differentiation and in determining the temporal and spatial patterns of development. In order to elucidate the mechanisms of human heart development, we have isolated a human homologue of the murine cardiac homeobox gene Csx (also called Nkx-2.5) and denoted it as CSX1. The amino acid sequence of the CSX1 homeodomain is 100% and 67% identical to that of murine Csx/Nkx-2.5 and Drosophila tinman, respectively. CSX1 has at least three isoforms generated by an alternative splicing mechanism. One of these isoforms (CSX1a) encodes a protein of approximately 35 kD that possesses the homeodomain, whereas the other two (CSX1b and CSX1c) encode a truncated protein of approximately 12 kD that is identical to the CSX1a protein at the amino-terminal 112 amino acids but lacks the homeodomain. Northern blot analysis showed that CSX1 transcripts are abundantly expressed in both fetal and adult hearts, but no signal was detected in other human tissues examined. Amplification of each isoform by reverse transcriptase-polymerase chain reaction revealed that all of the three isoforms are expressed in fetal and adult hearts and that the homeobox-containing isoform CSX1a is most abundant. The homeodomain-containing protein encoded by CSX1a binds to Csx/Nkx-2.5 binding sequences and transactivates the sequence-containing luciferase reporter gene. Unexpectedly, the homeodomain-lacking protein encoded by CSX1b also transactivates the reporter gene, although CSX1b does not bind to the Csx/Nkx-2.5 binding sequences. The highly conserved homeodomain sequence in evolution and the restricted expression in the heart suggest that CSX1 plays an important role in the development and differentiation of the human heart and that there may be two different mechanisms in transcriptional regulation by the CSX1 protein, homeodomain-dependent and -independent mechanisms.

Base Sequence↗
PubMed1985

Enzyme immunoassay for elcatonin, a synthetic analogue of eel calcitonin, in plasma.

An enzyme immunoassay for the direct measurement of elcatonin, a synthetic analogue of eel calcitonin with hypocalcemic activity, in rat and dog plasma was developed. Elcatonin was conjugated to beta-galactosidase using an N-succinimidyl ester, and the product was used as the tracer. The antibody-bound tracer was precipitated using a second antibody. The nonequilibrated procedure gave better sensitivity and precision than the equilibrated procedure. The nonequilibrated method was sensitive at quantifiable concentrations as low as 0.2 ng/mL using 0.1 mL of plasma and was also reproducible, with RSD values generally less than +/- 10%. Plasma levels in rats and dogs were determined by this competitive enzyme immunoassay after intramuscular or intravenous injection of 40 U/kg (8 micrograms/kg) of elcatonin.

Animals↗
PubMed1984

Enhanced rectal absorption of [Asu1,7]-eel calcitonin in rats using polyacrylic acid aqueous gel base.

The effects of polyacrylic acid aqueous gel on the absorption of rectally administered [Asu1,7]-eel calcitonin, a calcitonin analogue, were investigated in rats. The [Asu1,7]-eel calcitonin (1 U/kg) was given into the rectal loop in gel bases at various pH (5.5-8.5) and polyacrylic acid concentrations (0.01-1.0% w/v). The maximum hypocalcemic effect was obtained in approximately 30 min after administration of the analogue in a 0.1% w/v polyacrylic acid gel base at pH 5.5. The plasma calcium level decreased by approximately 18% from the initial level. Rectal administration in vehicles such as polyethylene glycol 1000, triglyceride fatty acid mixture base, or saline solution had little or no hypocalcemic effect at a dose of 5 U/kg. The results indicated that a polyacrylic acid aqueous gel base significantly improved the absorption of this analogue. Furthermore, rectal administration in a polyacrylic acid gel base (0.1% w/v; pH 5.5) required a dose 35 times greater than an intravenously administered dose to achieve an equivalent hypocalcemic effect.

Acrylic Resins↗
PubMed1979

[Degradation of ampicillin by urine of patients with complicated urinary tract infections and its protective effect of dicloxacillin (author's transl)].

In vitro enzymatic degradation rate of ampicillin (AB-PC) in urine of patients with complicated urinary tract infection and its protective effect of dicloxacillin (MDI-PC) was studied using a specific fluorometric assay for aminobenzylpenicilloic acid (AB-PA), which is converted from AB-PC by bacterial beta-lactamase. The results showed that average degradation rate of AB-PC in the urine of 10 patients were 12.2%, 21.5%, 34.3% and 48.2% at 15, 30, 60 and 120 minutes, respectively. While MDI-PC prevented the enzymatic transformation of AB-PC in such urinary samples and the average degradation rates at 15, 30, 60 and 120 minutes were considerably reduced to 7.7%, 12.2%, 21.6% and 32.8%, respectively. In vivo urinary excretion rate of AB-PA was compared between a total of 5 patients and 4 healthy volunteers after oral administration of 250 mg AB-PC. It was found that the patients excreted 9.1%, 10.7% and 12.7% of total dose at 0 approximately to 2 hours, 2 approximately to 4 hours, 4 approximately to 6 hours, respectively, while the average excretion rates in healthy volunteers were 1.54%, 2.88% and 7.94%, respectively. In 4 patients cross-over administration study, the combined dose of AB-PC and MDI-PC has been proved to clearly decrease the urinary excretion rate of AB-PA in 2 cases, but there was no significant difference in the average rate between the single and the combined dose.

Ampicillin↗