Biomedical subjects

Ayami Kondo

Publications and source records attributed to Ayami Kondo.

5 recordsLinked to original sources

PubMed2005

The role of the sympathetic nervous system in controlling bone metabolism.

Experimental studies have generally shown that increased sympathetic nervous activity causes bone loss via an increase in bone resorption and a decrease in bone formation. Increased bone resorption is based on the stimulation of both osteoclast formation and osteoclast activity. These effects are associated with beta2-adrenergic activity towards both osteoblastic and osteoclastic cells. Decreased bone formation is based on the inhibition of osteoblastic activity through beta2-adrenergic receptors on osteoblasts. Such findings indicate that beta-blockers may be effective against osteoporosis, in which case there is increased sympathetic activity. In fact, in a population-based, case-control study, the current use of beta-blockers has been demonstrated to be associated with a reduced risk of fractures. These clinical studies suggest that pharmacological blockade of the beta-adrenergic system is beneficial to the human skeleton. In another prospective study, however, no association between beta-blocker use and fracture risk was shown in perimenopausal and older women. To confirm this important new therapeutic avenue to prevent bone loss, the relationship between the pharmacological effectiveness of beta-blockers and the pathogenesis of osteoporosis must be explored in detail.

Adrenergic Agonists↗

PubMed2004

Activation of osteoblastic functions by a mediator of pain, bradykinin.

We investigated the effects of bradykinin (BK) on the production of interleukin (IL)-6 and prostaglandin PGE(2), whose molecules are capable of stimulating the development of osteoclasts from their hematopoietic precursors as well as the signal transduction systems involved, in human osteoblasts (SaM-1 cells). BK receptors B1 (B1R) and B2 (B2R) were expressed in SaM-1 and osteosarcoma (SaOS-2, HOS, and MG-63) cells. Treatment of SaM-1 cells with BK increased the synthesis of both IL-6 and PGE(2) and the increase in both was blocked by HOE140 (B2R antagonist), but not by Des-Arg(9)-[Leu(8)]-BK (B1R antagonist). U-73122, a phospholipase C (PLC) inhibitor, suppressed BK-induced IL-6 and PGE(2) synthesis in SaM-1 cells. In addition, BK caused an increase in the intracellular Ca(2+) concentration ([Ca(2+)]i), which was inhibited by pretreatment with HOE140 or 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) blocker. Furthermore, both SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]) and PD98059 (an inhibitor of MEK, upstream of ERK) attenuated the BK-induced IL-6 and PGE(2) synthesis. BK treatment resulted in the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK)1/2, and 2-APB could suppress BK-induced phosphorylation of ERK1/2. These findings suggest that BK increased both IL-6 and PGE(2) synthesis in osteoblastic cells via B2R and that PLC, IP(3)-induced [Ca(2+)]i, MEK, and MAPKs were involved in the signal transduction in these cells.

Bradykinin↗

PubMed2003

Regulated interaction between polypeptide chain elongation factor-1 complex with the 26S proteasome during Xenopus oocyte maturation.

BACKGROUND: During Xenopus oocyte maturation, the amount of a 48 kDa protein detected in the 26S proteasome fraction (p48) decreased markedly during oocyte maturation to the low levels seen in unfertilized eggs. The results indicate that the interaction of at least one protein with the 26S proteasome changes during oocyte maturation and early development. An alteration in proteasome function may be important for the regulation of developmental events, such as the rapid cell cycle, in the early embryo. In this study, we identified p48. RESULTS: p48 was purified by conventional column chromatography. The resulting purified fraction contained two other proteins with molecular masses of 30 (p30) and 37 (p37) kDa. cDNAs encode elongation factor-1gamma and delta were obtained by an immuno-screening method using polyclonal antibodies against purified p48 complex, which recognized p48 and p37. N-terminal amino acid sequence analysis of p30 revealed that it was identical to EF-1beta. To identify the p48 complex bound to the 26S proteasome as EF-1betagammadelta, antibodies were raised against the components of purified p48 complex. Recombinant EF-1 beta,gamma and delta were expressed in Escherichia coli, and an antibody was raised against purified recombinant EF-1gamma. Cross-reactivity of the antibodies toward the p48 complex and recombinant proteins showed it to be specific for each component. These results indicate that the p48 complex bound to the 26S proteasome is the EF-1 complex. MPF phosphorylated EF-1gamma was shown to bind to the 26S proteasome. When EF-1gamma is phosphorylated by MPF, the association is stabilized. CONCLUSION: p48 bound to the 26S proteasome is identified as the EF-1gamma. EF-1 complex is associated with the 26S proteasome in Xenopus oocytes and the interaction is stabilized by MPF-mediated phosphorylation.

Animals↗

PubMed2003

Activation of the peripheral sympathetic nervous system increased the expression of cyclooxygenase-2 (COX-2) mRNA in mouse calvaria.

Pharmacological stimulation of adrenoceptor was demonstrated to increase the synthesis of prostaglandin (PG)-E(2), well known to modulate bone metabolism by regulating development and function of osteoclasts and osteoblasts, in cultured osteoblastic cells. Recently, intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS), which caused the inflammatory stimuli in the brain, was demonstrated to increase the outflow of the peripheral sympathetic nervous system. In this study, to clarify the physiological role of sympathetic nerves to bone metabolism in vivo, we examined the effect of LPS (i.c.v.) on the expression of cyclooxygenase-2 (COX-2) mRNA in mouse calvaria, using reverse transcription-polymerase chain reaction analysis. The expression of COX-2 mRNA was increased by LPS (i.c.v.) in mouse calvaria. The treatment with the neurotoxin 6-hydroxydopamine or beta-blocker inhibited the central LPS-induced COX-2 mRNA in mouse calvaria. In addition, the treatment of calvaria with isoprenaline, beta-agonist, or noradrenaline increased PGE(2) synthesis in the organ culture system. These findings show that central LPS-induced COX-2 mRNA was mediated by the activation of postganglionic sympathetic nerve fibers and beta-adrenoceptor in mouse calvaria and suggest that in vivo activation of the sympathetic nervous system modulates bone metabolism.

Animals↗

PubMed2003

In vivo stimulation of sympathetic nervous system modulates osteoblastic activity in mouse calvaria.

Previously, we demonstrated that epinephrine induced the expression of interleukin (IL)-6 mRNA via beta-adrenoceptors in cultured human osteoblastic cells. IL-6 is well known to modulate bone metabolism by regulating the development and function of osteoclasts and osteoblasts. Recently, restraint stress and intracerebroventricular injection of lipopolysaccharide (LPS) have been reported to induce the expression of IL-6 mRNA in peripheral organs in mice in which expression is mediated by the activation of the sympathetic nervous system. To prove the physiological role of sympathetic nerves in bone metabolism in vivo, we examined by RT-PCR analysis the effects of restraint stress and intracerebroventricular injection of LPS on IL-6 mRNA expression in mouse calvaria. The expression of IL-6 mRNA in mouse calvaria was stimulated by either restraint stress (30 min) or intracerebroventricular injection of LPS (50 ng/mouse, 60 min). The treatment of mice with the neurotoxin 6-hydroxydopamine (6-OHDA, 100 mg x kg-1 x day-1 ip for 3 days) inhibited LPS (icv)-induced expression of IL-6 mRNA in their calvaria. The expression of IL-6 mRNA induced by the restraint stress was not influenced by 6-OHDA, which destroys noradrenergic nerve terminals. Furthermore, pretreatment with a beta-blocker, propranolol (15 or 25 mg/kg ip), inhibited both stress- and LPS-induced increases in the level of IL-6 mRNA, but pretreatment with an alpha-blocker, phentolamine (5 mg/kg sc), did not inhibit them in mouse calvaria. In addition, treatment of calvaria with isoprenaline or norepinephrine increased IL-6 synthesis in the organ culture system. These results indicate that in vivo adrenergic stimulation modulates the osteoblastic activity in mouse calvaria via noradrenergic nerve terminals.

Animals↗