Activation of c-Jun N-terminal kinase and p38 after cerebral ischemia upregulates cerebral sodium-glucose transporter type 1.

Cerebral ischemic stress increases cerebral sodium-glucose transporter type 1 (SGLT-1). However, the mechanism by which cerebral ischemia leads to the up-regulation of SGLT-1 remains unclear. In peripheral tissue, the activation of mitogen-activated protein kinases (MAPKs) increases SGLT-1. MAPK pathways [c-Jun N-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated protein kinase (ERK)] are activated by cerebral ischemic stress. Therefore, we confirmed the involvement of MAPKs in the up-regulation of cerebral SGLT-1 after cerebral ischemia. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO). Protein expression was assessed by western blotting. Mice received an intracerebroventricular (i.c.v.) injection of SP600125 (JNK inhibitor), SB203580 (p38 inhibitor), and PD98059 (MEK inhibitor) immediately after reperfusion. The infarction and behavioral abnormalities were assessed on days 1 and 3 after MCAO. The MAPK inhibitors suppressed the activation of JNK, p38, and ERK 3 h after MCAO. SP600125 and SB203580 administration ameliorated cerebral ischemic neuronal damage, whereas PD98059 administration exacerbated cerebral ischemic neuronal damage. SP600125 and SB203580 significantly suppressed the increase in SGLT-1 12 h after MCAO. PD98059 had no effect on SGLT-1 expression after MCAO. Our results indicate that the activation of JNK and p38 participate in the up-regulation of cerebral SGLT-1 after MCAO.

Identification and comparative analysis of the large subunit mitochondrial ribosomal proteins of Neurospora crassa.

The mitochondrial ribosome (mitoribosome) has highly evolved from its putative prokaryotic ancestor and varies considerably from one organism to another. To gain further insights into its structural and evolutionary characteristics, we have purified and identified individual mitochondrial ribosomal proteins of Neurospora crassa by mass spectrometry and compared them with those of the budding yeast Saccharomyces cerevisiae. Most of the mitochondrial ribosomal proteins of the two fungi are well conserved with each other, although the degree of conservation varies to a large extent. One of the N. crassa mitochondrial ribosomal proteins was found to be homologous to yeast Mhr1p that is involved in homologous DNA recombination and genome maintenance in yeast mitochondria.