Biomedical subjects

Noboru Sasagawa

Publications and source records attributed to Noboru Sasagawa.

21 records · Page 2Linked to original sources

PubMed2002

A secreted form of human ADAM9 has an alpha-secretase activity for APP.

ADAM9 (MDC9, meltrin gamma) is a member of the ADAM family of metalloproteases, which play important roles in cell-cell fusion, intracellular signaling, and other cellular functions. Here we cloned a novel form of human ADAM9, designated hADAM9s (s for short), which lacks the carboxyl-terminus. Human ADAM9s was found to be secreted from transfected COS cells. RT-PCR analysis demonstrated that the mRNA for hADAM9s is expressed in human brain, liver, heart, kidney, lung, and trachea. When hADAM9s was co-expressed in COS cells with APP and treated with phorbol ester, the APP was digested exclusively at the alpha-secretory site. These results suggest that hADAM9s has an alpha-secretase-like activity for APP. Non-amyloidgenic cleavage of APP may occur at the plasma membrane. Our new results support a new therapeutic strategy to decrease in the Abeta content by directly activating ADAM9 in the extracellular space.

ADAM Proteins↗

PubMed2002

Identification of a dopamine receptor from Caenorhabditis elegans.

The neurotransmitter dopamine regulates locomotion and egg laying in the nematode Caenorhabditis elegans. We have cloned a cDNA encoding the C. elegans G protein-coupled receptor (CeDOP1). The deduced amino acid sequence of the cloned cDNA shows high sequence similarities with D1-like dopamine receptors from other species. Three splice variants that differ in the length of the predicted third intracellular loop and C-terminal tail were identified. COS-7 cells transiently transfected with CeDOP1 showed high affinity binding to [(125)I]iodo-lysergic acid diethylamide (K(D)=3.43 +/- 0.83 nM). Dopamine showed the highest affinity (K(i)=0.186 microM) for this receptor among several vertebrate and invertebrate amine neurotransmitters tested, suggesting that the natural ligand for this receptor is dopamine.

Animals↗

PubMed2002

The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy.

Chloroquine myopathy is a drug poisoning disease involving rimmed vacuole formation. By Western blot analysis, we investigated posttranslational modification of LC3 in cultured cells with a high concentration of chloroquine, and found that the autophagosome membrane-bound form of LC3 increased dose-dependently. We also constructed a disease model by excessive chloroquine injection into rats and unusual immunohistochemical alteration was chased using anti-LC3 antibodies. With chloroquine treatment, muscle atrophy occurred predominantly in soleus muscle and unusual autophagosomes were accumulated. Therefore, we concluded that autophagy plays an important role in rimmed vacuole formation in certain muscular atrophies.

Animals↗