Neuroprotection Signaling of Nuclear Akt in Neuronal Cells

Akt is one of the central kinases that perform a pivotal function in mediating survival signaling in a wide range of neuronal cell types in response to growth factor stimulation. The recent findings of a number of targets for Akt suggest that it prohibits neuronal death by both impinging on the cytoplasmic cell death machinery and by regulating nuclear proteins. The presence of active Akt in the nuclei of mammalian cells is no longer debatable, and this has been corroborated by the finding of multiple targets in the nucleus of PC12 cells. However, it is also clear that the nuclear Akt signaling exists independent of the cytosolic Akt signaling, thereby showing a distinctive feature of nuclear Akt signaling as opposed to its cytosolic counterpart. The principal objective of this review is to summarize our current state of knowledge regarding nuclear Akt signaling in neuronal survival, and to introduce current theories regarding the roles of nuclear Akt in neuron.

Neuroprotection signaling pathway of nerve growth factor and brain-derived neurotrophic factor against staurosporine induced apoptosis in hippocampal H19-7 cells

Neurotrophins protect neurons against excitotoxicity; however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic morphology and caspase-3 activity by upregulating phosphorylation of the tropomyosin receptor kinase (Trk) receptor. Inhibition of Trk receptor by K252a altered the neuroprotective effect of both NGF and BDNF whereas inhibition of the p75 neurotrophin receptor (p75NTR) had no effect. Impairment of the PI3K/Akt pathway or overexpression of dominant negative (DN)-Akt abolished the protective effect of both neurotrophins, while active Akt prevented cell death. Moreover, knockdown of Akt by si-RNA was able to block the survival effect of both NGF and BDNF. Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.

Erratum

No abstract available.

Simvastatin inhibits induction of matrix metalloproteinase-9 in rat alveolar macrophages exposed to cigarette smoke extract

Matrix metalloproteinase-9 (MMP-9) may play an important role in emphysematous change in chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality and morbidity worldwide. We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, attenuates emphysematous change and MMP-9 induction in the lungs of rats exposed to cigarette smoke. However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients. Presently, we examined the related signaling for MMP-9 induction and the inhibitory mechanism of simvastatin on MMP-9 induction in AMs exposed to cigarette smoke extract (CSE). In isolated rat AMs, CSE induced MMP-9 expression and phosphorylation of ERK and Akt. A chemical inhibitor of MEK1/2 or PI3K reduced phosphorylation of ERK or Akt, respectively, and also inhibited CSE-mediated MMP-9 induction. Simvastatin reduced CSE-mediated MMP-9 induction, and simvastatin-mediated inhibition was reversed by farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). Similar to simvastatin, inhibition of FPP transferase or GGPP transferase suppressed CSE-mediated MMP-9 induction. Simvastatin attenuated CSE-mediated activation of RAS and phosphorylation of ERK, Akt, p65, IkappaB, and nuclear AP-1 or NF-kappaB activity. Taken together, these results suggest that simvastatin may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of RAS in the signaling pathways, in which Raf-MEK-ERK, PI3K/Akt, AP-1, and IkappaB-NF-kappaB are involved.

Characterization of Korean Leptospira interrogans Isolates by Pulsed-Field Gel Electrophoresis of Not I Digests of DNA / 감염과화학요법

BACKGROUND: Many strains of Leptospira interrogans have been isolated in Korea since 1984. Most isolates were identified as serovar lai by serological methods. The pulsed field gel electrophoresis (PFGE) patterns of Korean isolates have not been investigated currently. METHODS: 29 reference strains and 29 Korean isolates of Leptospira interrogans were characterized by PFGE. Chromosomes were digested by the Not I restriction enzyme and subsequently PFGE was performed in CHEF-DRII (Bio Rad Lab) with 3 pulse times (30 seconds 13 hours, 60 seconds 13 hours, 120 seconds 14 hours) at 150 V (4.5 V/cm). RESULTS: 12 serogroup reference strains and most 17 serovars reference strains in the serogroup Icterohaemoffhagie showed the unique Not I restriction patterns. Most isolates identified serologically as serovar lai showed the same PFGE patterns as the serovar lai reference strain. The strain HM3 and 18R identified serologically as new serovars yeonchon and hongchon respectively showed the same PFGE patterns as serovar lai. The strain AP31, CH88-19 and NR13 that were different from serovar lai by serological methods showed the PFGE patterns indistinguishable from serovar lai reference strain. The strain HY2 that was identified as serovar lai, and the strain 30R that was different from serovar lai serologically showed the PFGE patterns slightly different from serovar lai reference strain. CONCLUSION: The PFGE profile of most Korean isolates Leptospira interrogans serologically identified as serovar lai is identical to the reference strain serovar lai. PFGE analysis thus may be applied to identify serovar of isolates and to investigate the genetic diversity of related serovar.

Characterization of Korean Leptospira interrogans Isolates by Pulsed-Field Gel Electrophoresis of Not I Digests of DNA / 감염과화학요법

BACKGROUND: Many strains of Leptospira interrogans have been isolated in Korea since 1984. Most isolates were identified as serovar lai by serological methods. The pulsed field gel electrophoresis (PFGE) patterns of Korean isolates have not been investigated currently. METHODS: 29 reference strains and 29 Korean isolates of Leptospira interrogans were characterized by PFGE. Chromosomes were digested by the Not I restriction enzyme and subsequently PFGE was performed in CHEF-DRII (Bio Rad Lab) with 3 pulse times (30 seconds 13 hours, 60 seconds 13 hours, 120 seconds 14 hours) at 150 V (4.5 V/cm). RESULTS: 12 serogroup reference strains and most 17 serovars reference strains in the serogroup Icterohaemoffhagie showed the unique Not I restriction patterns. Most isolates identified serologically as serovar lai showed the same PFGE patterns as the serovar lai reference strain. The strain HM3 and 18R identified serologically as new serovars yeonchon and hongchon respectively showed the same PFGE patterns as serovar lai. The strain AP31, CH88-19 and NR13 that were different from serovar lai by serological methods showed the PFGE patterns indistinguishable from serovar lai reference strain. The strain HY2 that was identified as serovar lai, and the strain 30R that was different from serovar lai serologically showed the PFGE patterns slightly different from serovar lai reference strain. CONCLUSION: The PFGE profile of most Korean isolates Leptospira interrogans serologically identified as serovar lai is identical to the reference strain serovar lai. PFGE analysis thus may be applied to identify serovar of isolates and to investigate the genetic diversity of related serovar.