||HOSSAIN MD. SHAMIM, Masataka Ifuku, Sachiko Take, Jun Kawamura, Miake, Kiyotaka, Toshihiko Katafuchi, Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling, PLOSone, DOI: 10.1371/journal.pone.0083508, 2013.12, Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer’s patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders..
||Lei Li, Sachio Morimoto, Sachiko Take, Dong-Yun Zhan, Cheng-Kun Du, Yuan-Yuan Wang, Xue-Li Fan, Tatsuya Yoshihara, Fumi Takahashi, Toshihiko Katafuchi, Toshiyuki Sasaguri, Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure, Journal of Molecular and Cellular Cardiology, Volume 53, Issue 6, 760-767, 2012.12, Inherited or non-inherited dilated cardiomyopathy (DCM) patients develop varied disease phenotypes leading to death after developing congestive heart failure (HF) or sudden death with mild or no overt HF symptoms, suggesting that environmental and/or genetic factors may modify the disease phenotype of DCM. In this study, we sought to explore unknown genetic factors affecting the disease phenotype of monogenic inherited human DCM. Knock-in mice bearing a sarcomeric protein mutation that causes DCM were created on different genetic backgrounds; BALB/c and C57Bl/6. DCM mice on the BALB/c background showed cardiac enlargement and systolic dysfunction and developed congestive HF before died. In contrast, DCM mice on the C57Bl/6 background developed no overt HF symptoms and died suddenly, although they showed considerable cardiac enlargement and systolic dysfunction. BALB/c mice have brain serotonin dysfunction due to a single nucleotide polymorphism (SNP) in tryptophan hydroxylase 2 (TPH2). Brain serotonin dysfunction plays a critical role in depression and anxiety and BALB/c mice exhibit depression- and anxiety-related behaviors. Since depression is common and associated with poor prognosis in HF patients, we examined therapeutic effects of anti-depression drug paroxetine and anti-anxiety drug buspirone that could improve the brain serotonin function in mice. Both drugs reduced cardiac enlargement and improved systolic dysfunction and symptoms of severe congestive HF in DCM mice on the BALB/c background. These results strongly suggest that genetic backgrounds involving brain serotonin dysfunction, such as TPH2 gene SNP, may play an important role in the development of congestive HF in DCM..
||Katafuchi, T., Duan, S., Take, S. and Yoshimura, M., Cytokine-induced suppression of medial preoptic neurons: Mechanisms and neuromodulatory effects, Annals of the New York Academy of Sciences, 1153, 76-81, 2009.02.
||Katafuchi, T., Kondo T., Take, S., Yoshimura, Brain cytokines and 5-HT in fatigue., Ann. NY. Acad. Sci., 2006.12.
||Katafuchi, T., Kondo, T., Take, S. and Yoshimura, M., Involvement of enhanced expression of brain interferon-α and serotonin transporter in poly I:C-induced fatigue in rats., Eur. J. Neurosci., in press, 2005.01.
||Katafuchi, T., Duan, S., Take, S. and Yoshimura, M., Modulation of glutamate-induced outward current by prostaglandin E2 in rat dissociated preoptic neurons., Brain Res., 10.1016/j.brainres.2005.01.002, 1037, 1-2, 180-186, 1037: 180-186, 2005.01.
||Katafuchi. T., Kondo, T., Yasaka, K., Kubo, K., Take, S. and Yoshimura, M., Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-α mRNA in rats: a model for immunologically induced fatigue., Neuroscience, 10.1016/S0306-4522(03)00365-8, 120, 3, 837-845, 120: 837-845, 2003.01.
||Katafuchi, T., Takaki, A., Take, S., Kondo, T. and Yoshimura, M., Endotoxin inhibitor blocks heat exposure-induced expression of brain cytokine mRNA in aged rats., Mol. Brain Res., 10.1016/S0169-328X(03)00331-0, 118, 1-2, 24-32, 118: 24-32, 2003.01.