RESUMEN
Inhibitory PAS domain protein (IPAS), a repressor of hypoxia-inducible factor-dependent transcription under hypoxia, was found to exert pro-apoptotic activity in oxidative stress-induced cell death. However, physiological and pathological processes associated with this activity are not known. Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. Activation of the PINK1-Parkin pathway attenuated IPAS-dependent apoptosis. IPAS was markedly induced in the midbrain following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and IPAS-deficient mice showed resistance to MPTP-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A significant increase in IPAS expression was found in SNpc neurons in patients with sporadic PD. These results indicate a mechanism of neurodegeneration in PD.
RESUMEN
The red cell Kell phenotypes were examined in 15 Japanese patients with chronic granulomatous disease. No McLeod type was found. A low incidence of the association of chronic granulomatous disease with the McLeod type in the Japanese is suggested.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Enfermedad Granulomatosa Crónica/sangre , Sistema del Grupo Sanguíneo de Kell/genética , Femenino , Humanos , Japón , Masculino , FenotipoRESUMEN
Anti-Jsa was found in a Japanese female who had never received a transfusion and had borne 3 Jsa-negative children. The antibody agglutinated Jsa cells suspended in saline and treated with proteolytic enzymes as well as reacting with those cells by the indirect antiglobulin test. This example is the first reported 'naturally occurring' anti-Jsa.
Asunto(s)
Antígenos de Grupos Sanguíneos , Sistema del Grupo Sanguíneo de Kell , Absorción , Adsorción , Anticuerpos , Prueba de Coombs , Femenino , Humanos , Japón , Persona de Mediana Edad , Péptido Hidrolasas/farmacologíaRESUMEN
'Naturally occurring' anti-Kell (K1) was found in a Japanese male who has never received a transfusion. The antibody agglutinated K:1 cells suspended in saline at 4 and 22 degrees C as well as cells suspended in albumin and treated with proteolytic enzymes.
