Biomedical subjects

Tadashi Kurihara

Publications and source records attributed to Tadashi Kurihara.

4 recordsLinked to original sources

PubMed2003

Suppression of lipopolysaccharide-dependent tumor necrosis factor alpha induction in rat microglia, in which protein kinase C alpha is down-regulated.

Microglia are thought to produce a cytotoxic cytokine, tumor necrosis factor alpha (TNF alpha), in the pathological brain. Thus, the mechanism that suppresses the induction of TNF alpha in microglia is of interest. We found that lipopolysaccharide (LPS)-induced TNF alpha is strongly suppressed by pretreatment with specific protein kinase C (PKC) inhibitors, Gö6976 and bisindolylmaleimide, suggesting that PKC alpha plays a role in the signaling cascade of TNF alpha induction. Therefore, the association of PKC alpha with TNF alpha induction was investigated in PKC alpha-deficient microglia prepared by pretreatment with phorbol-12-myristate-13-acetate (PMA). PMA-pretreated microglia strongly decreased the TNF alpha induction in the absence of PKC alpha when activated with LPS. The lack of PKC alpha in the PMA-treated microglia was confirmed by determining conventional PKC activity. Taken together, the present study demonstrated that PKC alpha is a requisite PKC isoform in the signaling cascade of TNF alpha induction in LPS-stimulated microglia.

Animals↗

PubMed2003

Activation of microglia with lipopolysaccharide leads to the prolonged decrease of conventional protein kinase C activity.

The activation of microglia by lipopolysaccharide (LPS) results in the induction of harmful factors including nitric oxide and tumor necrosis factor alpha (TNFalpha). Such microglial activation was suggested to be mediated by PKC activity based on the results of an inhibitor experiment. To clarify the relationship between microglial activation and PKC activity, conventional PKC (cPKC) activity was measured by enzyme-linked immunosorbent assay (ELISA) in LPS-activated microglia. LPS stimulation caused a time- and dose-dependent decrease (70%) of specific activity of cPKC, ascribed to the decreasing amounts of PKCalpha. However, the remaining PKC activity (30%) was sustained despite longer incubation or higher LPS concentration. Therefore, it is suggested that LPS-stimulated microglia require priming by PKC activation for the induction of harmful factors, while only a part (30%) of original PKC activity is sufficient for durable microglial activation.

Animals↗

PubMed2002

Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro.

In analyzing the regulation of neurotrophin production/secretion from microglia, C8-ceramide (D-erythro-sphingosine, N-octanoyl-) was found to induce secretion of brain-derived neurotrophic factor (BDNF) from microglia in vitro. In the present study, the action of C8-ceramide in secreting neurotrophic and harmful factors was investigated and compared with the effects of lipopolysaccharide (LPS). C8-ceramide as well as LPS enhanced the production/secretion of BDNF but, different from LPS, did not induce tumor necrosis factor alpha, interleukin-1beta, or nitric oxide. The C8-ceramide-induced BDNF release was significantly suppressed by protein kinase C (PKC) inhibitor, bisindolylmaleimide, which targets PKC isoforms, alpha, beta, gamma, delta and epsilon. However, it was not suppressed by a specific inhibitor of PKCalpha. Furthermore, PKCbeta and gamma were undetected in the microglia. Therefore, PKCdelta and/or epsilon appear to be functioning PKC isoforms. In contrast, none of the mitogen-activated protein kinases (MAPKs) and none of the transcription factors, including the cAMP response element-binding transcription factor (CREB) and nuclear factor kappaB (NFkappaB) were activated in the microglia in response to C8-ceramide. These results indicate that ceramide-induced BDNF release in microglia is mediated by a signaling pathway associated with PKCdelta and/or epsilon, but not with activation of MAPKs, CREB and NFkappaB.

Animals↗

PubMed2002

Scintigraphic assessment of patients with electrocardiographic left ventricular hypertrophy with ST-T changes without apparent cause.

PURPOSE: Some patients who show electrocardiographic left ventricular hypertrophy with ST-T changes (ECG-LVH) are difficult to evaluate using routine examinations. To clarify the pathologic process in these patients, the authors performed several scintigraphic examinations. MATERIALS AND METHODS: Twenty-nine patients with ECG-LVH, without apparent cause, such as left ventricular (LV) systolic overloading or increased LV mass, were examined by myocardial I-123 MIBG imaging, I-123 BMIPP imaging, and exercise-induced stress perfusion imaging. In addition to the visual assessment of each image, we calculated global and regional myocardial washout of I-123 MIBG (%washout). The LV was assessed using conventional echocardiography. RESULTS: Visually observed abnormalities were located exclusively at the LV apex with all imaging methods and were detected in 76%, 52%, and 17% of patients by I-123 MIBG, I-123 BMIPP, and perfusion imaging, respectively. A follow-up study revealed that the apical defects of I-123 MIBG were subsequently followed by defects of I-123 BMIPP and then perfusion abnormalities. In patients with an apical defect revealed by I-123 MIBG imaging, apical %washout was high. In nine patients who underwent myocardial biopsy, myocardial disarray was observed at the apical regions. CONCLUSIONS: In many patients with ECG-LVH without apparent cause, sympathetic abnormalities are observed at the apex, similar to pathologic changes in hypertrophic cardiomyopathy. These abnormalities may lead to changes in fatty acid metabolism and perfusion.

3-Iodobenzylguanidine↗