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1.
Front Plant Sci ; 8: 772, 2017.
Article in English | MEDLINE | ID: mdl-28553305

ABSTRACT

Stomata are the main gateways for water and air transport between leaves and the environment. Inward-rectifying potassium channels regulate photo-induced stomatal opening. Rice contains three inward rectifying shaker-like potassium channel proteins, OsKAT1, OsKAT2, and OsKAT3. Among these, only OsKAT2 is specifically expressed in guard cells. Here, we investigated the functions of OsKAT2 in stomatal regulation using three dominant negative mutant proteins, OsKAT2(T235R), OsKAT2(T285A) and OsKAT2(T285D), which are altered in amino acids in the channel pore and at a phosphorylation site. Yeast complementation and patch clamp assays showed that all three mutant proteins lost channel activity. However, among plants overexpressing these mutant proteins, only plants overexpressing OsKAT2(T235R) showed significantly less water loss than the control. Moreover, overexpression of this mutant protein led to delayed photo-induced stomatal opening and increased drought tolerance. Our results indicate that OsKAT2 is an inward- rectifying shaker-like potassium channel that mainly functions in stomatal opening. Interestingly, overexpression of OsKAT2(T235R) did not cause serious defects in growth or yield in rice, suggesting that OsKAT2 is a potential target for engineering plants with improved drought tolerance without yield penalty.

2.
Clin Exp Pharmacol Physiol ; 44(6): 671-679, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28370165

ABSTRACT

Excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischaemic brain injury. Therefore, PARP-1 inhibition after ischaemic stroke has been attempted in successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischaemic injury in an in vitro model. The half-life of JPI-289 after intravenous or oral administration in rats was relatively long (1.4-1.5 hours) with 65.6% bioavailability. The inhibitor strongly inhibited PARP-1 activity (IC50 =18.5 nmol/L) and cellular PAR formation (IC50 =10.7 nmol/L) in the nanomolar range. In rat cortical neuronal cells, JPI-289 did not affect cell viability up to 1 mmol/L as assayed by Trypan blue staining (TBS) and lactate dehydrogenase (LDH) assay. Treatment of JPI-289 for 2 hours after 2 hours of oxygen glucose deprived (OGD) rat cortical neuron attenuated PARP activity and restored ATP and NAD+ levels. Apoptosis-associated molecules such as apoptosis inducing factor (AIF), cytochrome C and cleaved caspase-3 were reduced after JPI-289 treatment in the OGD model. The present findings suggest that the novel PARP-1 inhibitor, JPI-289, is a potential neuroprotective agent which could be useful as a treatment for acute ischaemic stroke.


Subject(s)
Brain/cytology , Enzyme Inhibitors/pharmacology , Naphthyridines/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Animals , Apoptosis/drug effects , Brain/drug effects , Cell Hypoxia/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Intracellular Space/drug effects , Intracellular Space/metabolism , Naphthyridines/chemistry , Naphthyridines/pharmacokinetics , Neurons/cytology , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacokinetics , Rats , Signal Transduction/drug effects , Solubility
3.
Muscle Nerve ; 38(4): 1336-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18816602

ABSTRACT

We report the clinical characteristics, genetic analysis, and muscle biopsy findings of a family with Emery-Dreifuss muscular dystrophy and a novel mutation (Leu162Pro) in the LMNA gene. Within this single family, the age of onset and disease severity varied among the family members. In addition, focal defects of nuclear membranes with chromatin blebs in endothelial cells was shown via electron microscopy.


Subject(s)
Genes, Recessive/genetics , Genetic Predisposition to Disease/genetics , Lamin Type A/genetics , Muscular Dystrophy, Emery-Dreifuss/diagnosis , Muscular Dystrophy, Emery-Dreifuss/genetics , Point Mutation/genetics , Adult , Age of Onset , Amino Acid Substitution/genetics , Chromatin/pathology , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Chromosome Disorders/physiopathology , DNA Mutational Analysis , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Genetic Markers , Humans , Leucine/genetics , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Emery-Dreifuss/physiopathology , Nuclear Envelope/metabolism , Nuclear Envelope/pathology , Pedigree , Proline/genetics
4.
Exp Neurol ; 205(2): 336-46, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17433298

ABSTRACT

Glycogen synthase kinase (GSK)-3 has recently been implicated in the pathogenesis of neurodegenerative diseases. Although the neuroprotective effects of GSK-3 inhibitors in Alzheimer's disease have been established, their effects on amyotrophic lateral sclerosis (ALS) have not been well defined. This study was undertaken to evaluate the effects of GSK-3 inhibition in the G93A-SOD1 mouse model of ALS. Groups of G93A-SOD1 mice were treated with varying concentrations of GSK-3 inhibitor VIII, a specific GSK-3 inhibitor that crosses the BBB, intraperitoneally 5 days a week after 60 days of age. The GSK-3 inhibitor VIII treatment significantly delayed the onset of symptoms and prolonged the life span of the animals, and inhibited the activity of GSK-3 in a concentration-dependent manner. Furthermore, this treatment preserved survival signals and attenuated death and inflammatory signals. These data suggest that GSK-3 plays an important role in the pathogenic mechanisms of ALS and that inhibition of GSK-3 could be a potential therapeutic candidate for ALS.


Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/genetics , Enzyme Inhibitors/therapeutic use , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/genetics , Superoxide Dismutase/genetics , Amyotrophic Lateral Sclerosis/pathology , Animals , Blotting, Western , Caspase 3/metabolism , Cell Death/drug effects , Cyclooxygenase 2/metabolism , Cytochromes c/metabolism , Cytosol/enzymology , Disease Progression , Humans , In Situ Nick-End Labeling , Intercellular Adhesion Molecule-1/metabolism , Mice , Mice, Transgenic , Motor Neurons/pathology , Poly(ADP-ribose) Polymerases/metabolism , Postural Balance/drug effects , Spinal Cord/metabolism , Spinal Cord/pathology , Superoxide Dismutase-1 , Thiazoles/therapeutic use , Urea/analogs & derivatives , Urea/therapeutic use
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