Cadmium-induced Apoptosis in HL-60 Cells Via Signal Transduction / 대한산업의학회지

OBJECTIVES: Apoptosis is a process of active cell death, distinct from necrosis and characterized by specific morphological and biochemical features. Apoptosis induced by metals and metal-related deleterious conditions has only recently been studied. Although the toxic effects of heavy metals are well described, little is known about the mechanism of apoptosis via cadmium toxicity. Therefore, this study is designed to define the induction mechanism of apoptosis by which cadmium exerts its cytotoxic effect on human promyelocytic leukemic HL-60 cells. The cytotoxic effects of cadmium on HL-60 cells are studied in regards to apoptotic signal transduction pathways. METHODS: The mode of cadmium-induced apoptosis was investigated in HL-60 cells. HL-60 cells were treated with various concentrations of cadmium and antioxidants after which the viability of the cells were measured by MTT assay. The morphological features of cadmium- induced apoptosis were evaluated by fluoromicroscopy and the DNA fragmentation was analyzed using 1.5% agarose gel electrophorosis. Kinase activity was assayed by autoradiography and activity of NF-kappaB and nuclear proteins were measured by EMSA. RESULTS: Cadmium (125 microM) induces the characteristic morphological features of apoptosis, which are characterized by a shrinkage of the cytoplasm and a condensation of chromatin. In addition, cadmium induced the ladder pattern of DNA fragmentation. Antioxidants(Sodium nitroprusside, glutathione and N-acethylcysteine), which were not toxic to the cells, did not suppress apoptosis induced by cadmium. Cadmium enhances the expression of several classes of genes at elevated cytotoxic concentrations. Poly(ADP-ribose) polymerase(PARP) was predominantly in the fragmented form when doses of 125 microM were used. Since PARP is cleaved by CPP32 (caspase-3), we next determined if cadmium was capable of effecting changes in CPP32 activity. The results of these experiments showed that cadmium increased caspase-3 activity in a time dependent manner, corresponding to the time of appearance of fragmented PARP. Cadmium also increased the phosphotransferase activities of c-JUN N-terminal kinase (JNK). Furthermore, cadmium increased the activation of transcriptional factors including the activation of protein-1 (AP-1) and NF-kappaB . CONCLUSIONS: These results suggest that cadmium induces the apoptotic death of HL-60 cells via the activation of a DEVD-specific caspase, JNK and transcriptional factors such as AP-1 and NF-kappaB .

Visualization and Quantitative Analysis of Bulbar Palsy and Its Progression Using Sound Spectrography: A case report

Distortion of vowels in dysarthria associated with amyotrophic lateral sclerosis can be detected at the perceptual, physiological, and acoustical levels of analysis. Sound spectrography was used to analyse the formants of vowels which reflect position and space of articulatory organs. We analyse status and progression of dysarthria in 54 year old women with amyotrophic lateral sclerosis using sound spectrography. Target formant frequencies were measured from select words containing the vowels /a/, /e/, /i/, /o/, /u/. Results revealed that dysarthric patient exhibited smaller vowel space areas and less systematic changes in vowel spaces for pronouncing different vowels in comparison with normal control. Changes of vowel formants in sound spectrographic analysis reflected progression of dysarthric symptom in this patient. We conclude that acoustic analysis of vowels using sound spectrography is a useful tool to visualize and quantitatively analyse the severity and progression of dysarthria due to paralytic articulatory organ.

The Effect of Sprint and Heavy Resistance Training on Muscle Strength, Endurance and Muscle Fiber Type

OBJECTIVE: The purpose of this study is to compare muscle strength, endurance and the change of myosin heavy chain isoform after sprint training(ST) and heavy resistance training(HRT). METHOD: Fourteen young athletes were enrolled and were randomly assigned into each training group. Before and after training for 8 weeks, the strength and the endurance were evaluated using isokinetic exercise system(Cybex 6000). The specimens of muscle biopsy were obtained from vastus lateralis muscle and were analysed for muscle fiber type using one dimensional electrophoresis. RESULTS: Peak torque, total work and mean power were increased significantly in both groups, but endurance ratio increased only in the sprint training group(P0.05). CONCLUSION: This study shows that it is possible to increase muscle strength and to achieve fiber type transformation with the sprint training and the high resistance training.

Sacral Dermatomal Somatosensory Evoked Potentials Its Techniques and Clinical Significance

Pudendal nerve somatosensory evoked potential (PSEP) study has been utilized for the evaluation of neurogenic dysfunctions of bowel, bladder and sex. However, the reluctance of sexual organ exposure during the study can be a serions limiting factor. Sacral dermatomal somatosensory evoked potential (SDSEP) study stimulating sacral dermatome can be an alternative or a supportive method for the PSEP study. The purpose of this study is to present the techniques, normal values and clinical significance of SDSEP study in spinal cord injured patients. Thirty control subjects and thirty-five spinal cord injured patients were enrolled for the study. Using ring electrodes, S3 dermatome was stimulated by Nicolet Viking IV EMG/EP system. Evoked responses were recorded at the cortex(Cz'-Fz) by the needle electrodes. The latencies and amplitudes of SDSEP and PSEP responses were obtained and analyzed. In control subjects, the P1 latencies of SDSEP were 34.72+/-2.68 msec for the right and 33.54+/-1.95 msec for the left. The N1 latencies were 43.06+/-2.31 msec for the right and 42.14+/-2.29 msec for the left, respectively. The P1N1 amplitudes of control subjects were 0.73+/-0.40 V for the right and 0.69+/-0.22 V for the left. The coincidence of SDSEP and PSEP was 86.7% of the spinal cord injured patients. In conclusion, SDSEP study could be used for the evaluation of neurogenic dysfunctions of bladder, bowel, and sex in conjunction with the PSEP study.