Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury

Oxidative stress is critical for causing cardiac injuries during ischemia-reperfusion (IR), yet the molecular mechanism for this remains unclear. In the present study, we observe that hypoxia and reoxygenation, a component of ischemia, effectively induces apoptosis in the cardiac myocytes from neonatal rats and it concomitantly leads to induction of GADD153, an apoptosis-related gene. Furthermore, IR injury of rat heart showed a GADD153 overexpression in the ischemic area where the TUNEL reaction was positive. A downregulation of cardiac ankyrin repeat protein (CARP) was also observed in this ischemic area. Promoter deletion and reporter analysis revealed that hypoxia transcriptionally activates a GADD153 promoter through the AP-1 element in neonatal cardiomyocytes. Ectopic overexpression of GADD153 resulted in the downregulation of CARP expression. Accordingly, the induction of GADD153 mRNA were followed by the CARP down-regulation in an in vivo rat coronary ischemia/reperfusion injury model. These results suggest that GADD153 over-expression and the resulting downregulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.

The Usefulness of 3D-Surface Rendering of the MRI in Surgical Treatment of Patients with Intractable Neocortical Epilepsy

BACKGROUND: This study is designed to indicate the role of 3D-surface rendering of the MRI in defining and resect-ing the epileptogenic zone. METHODS: 25 healthy volunteers and 55 patients were studied. Conventional MRI and 3D-surface rendering were performed. Sulcal and gyral patterns were assesed by a neuroradiologist and a neurologist with-out the clinical informations. Chronic video-EEG monitoring with surface and subdural grid electrodes, and PET were done. Resection was performed based on data of the EEG recordings and 3D-surface rendering. RESULTS: Conventional MRI identified structural abnormality ("MRI-identifiable lesion") in 20 patients. 20 of 35 patients without structural abnormality in conventional MRI revealed abnormal sulcal and gyral patterns in 3D-surface rendering of MRI ("3D-identifiable lesion"). Subdural grid EEGs recorded focal or diffuse ictal EEG onset from the region of "3D-identifiable lesion". Histopathologic findings revealed cortical dysplasia in 48 and neocortical gliosis in seven. Overall surgical out-come, at the average follow up period of 32.5 months, showed class I in 63.6%, class II in 25.5%, and class III in 10.9%. Among 20 patients with "MRI-identifiable lesion", 80% were in class I and 20% were in class II. Among 35 patients without "MRI-identifiable lesion", 54.3% were in class I, 28.6% were class II, and 17.1% were in class III. 80% of 20 patients with "3D-identifiable lesion" showed class I and 20% of 15 patients without "3D-identifiable lesion" showed class I. CONCLUSIONS: Identification of "MRI-identifiable lesion" or "3D-identifiable lesion" was of value in defining the epileptogenic zone. Resection of "MRI-identifiable lesion" or "3D-identifiable lesion", which were epilep-togenic in EEGs, promised a good surgical outcome.

Effects of Propofol on the Cytosolic Calcium Concentration of the Astrocytoma Cells / 대한마취과학회지

BACKGROUND: Propofol is a widely-used intravenous anesthetic with a rapid onset, short duration of action and rapid elimination but the molecular mechanisms of action are not completely understood. Not only neurons but astrocytes are potential substrates for anesthetics, specifically for propofol. Intracellular calcium ion ([Ca2 ]i) is known to play a key role in the transduction and propagation of various chemical signals in astrocytes. METHODS: In the present study, the effects of propofol on the intracellular calcium concentration of astrocytoma cells by using a fura-2 fluorescence spectroscopy was investigated. RESULTS: In an isotonic standard solution, propofol (50 and 500microM) produced a transient increase in [Ca2 ]i while the intralipid did not change [Ca2 ]i. In several cells (20%), a transient increase in [Ca2 ]i was followed by sustained elevation which was sensitive to depletion of external calcium. A propofol-induced increase in [Ca2 ]i was not altered by an L-type calcium channel blocker (nifedipine 2microM). In cells bathed in a Ca2 -free external solution, a transient increase in [Ca2 ]i was observed. After the pretreatment of cyclopiazonic acid (CPA), an endoplasmic reticulum Ca2 -ATPase blocker, propofol 500microM did not produce any significant increase in [Ca2 ]i. Carbachol, which is known to release calcium from the inositol 1,4,5-triphosphate (IP3)-induced calcium release (IICR) stores, prevented the [Ca2 ]i increase by propofol and vice versa. High concentrations of caffeine (10 mM), which release calcium from the calcium-induced calcium release (CICR) stores, had no effect on [Ca2 ]i. CONCLUSIONS: From the above results, it is suggested that an increase in [Ca2 ]i by propofol in astrocytoma cells is mainly due to calcium release from the IICR stores.