1.Arsenic Trioxide Induces Apoptosis of HL-60 Cells via Activation of Intrinsic Caspase Protease with Mitochondrial Dysfunction.
Byung Hak JUNG ; Channy PARK ; Hak Ryul KIM ; Moo Rim PARK
Cancer Research and Treatment 2002;34(4):308-315
Arsenic trioxide (As2O3) was introduced into the treatment of refractory or relapsed acute promyelocytic leukemia and showed a striking effectiveness in China and United States multicenter study. However, the mechanistic basis for the carcinogenic or therapeutic effects of arsenics is still poorly understood. So, this study is performed to determine whether As2O3 induces apoptosis through intrinsic caspase cascades in acute promyelocytic leukemia HL-60 cells. MATERIALS AND METHODS: HL-60 cells were treated with As2O3 to investigate apoptosis through signaling of caspase cascades and mitochondrial dysfunction. RESULTS: As2O3 (>0.5 uM) decreased the viability of HL-60 cells in a dose-dependent manner, which was revealed as apoptosis shown chromatin condensation and ladder pattern DNA fragmentation. As2O3 increased the catalytic activity of caspase family cysteine proteases including caspase-3 and -9 proteases. Consistently, PARP, an intracellular biosubstrate of caspase-3 protease, was cleaved from 116 kDa to 85 kDa fragments. It also induced the change of mitochondrial membrane potential. Morever, As2O3 resulted in the increase of Bak. CONCLUSION: These data suggest that As2O3 induces apoptosis of HL-60 cells through activation of intrinsic caspase protease with mitochondrial dysfunction.
Apoptosis*
;
Arsenic*
;
Caspase 3
;
China
;
Chromatin
;
Cysteine Proteases
;
DNA Fragmentation
;
HL-60 Cells*
;
Humans
;
Leukemia, Promyelocytic, Acute
;
Membrane Potential, Mitochondrial
;
Peptide Hydrolases
;
Strikes, Employee
;
United States
2.Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure.
Ju Hwan KIM ; Da Hyeon YU ; Hak Rim KIM
The Korean Journal of Physiology and Pharmacology 2017;21(2):179-188
With the explosive increase in exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones, public concerns have grown over the last few decades with regard to the potential effects of EMF exposure on the nervous system in the brain. Many researchers have suggested that RF-EMFs can effect diverse neuronal alterations in the brain, thereby affecting neuronal functions as well as behavior. Previously, we showed that long-term exposure to 835 MHz RF-EMF induces autophagy in the mice brain. In this study, we explore whether short-term exposure to RF-EMF leads to the autophagy pathway in the cerebral cortex and brainstem at 835 MHz with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Increased levels of autophagy genes and proteins such as LC3B-II and Beclin1 were demonstrated and the accumulation of autophagosomes and autolysosomes was observed in cortical neurons whereas apoptosis pathways were up-regulated in the brainstem but not in the cortex following 4 weeks of RF exposure. Taken together, the present study indicates that monthly exposure to RF-EMF induces autophagy in the cerebral cortex and suggests that autophagic degradation in cortical neurons against a stress of 835 MHz RF during 4 weeks could correspond to adaptation to the RF stress environment. However, activation of apoptosis rather than autophagy in the brainstem is suggesting the differential responses to the RF-EMF stresses in the brain system.
Absorption
;
Animals
;
Apoptosis*
;
Autophagy*
;
Brain
;
Brain Stem*
;
Cell Phones
;
Cerebral Cortex*
;
Electromagnetic Fields
;
Mice
;
Nervous System
;
Neurons
3.Inactivation of Mad2B Enhances Apoptosis in Human Cervical Cancer Cell Line upon Cisplatin-Induced DNA Damage
Ju Hwan KIM ; Hak Rim KIM ; Rajnikant PATEL
Biomolecules & Therapeutics 2023;31(3):340-349
Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results sug-gest that Mad2B may be a critical modulator of DNA damage response.
4.A Case Report: Implantation of Balloon-Expandable Stent for Coarctation of the Aorta, Associated with Congenital Mitral Stenosis.
Seung Hyuk CHOI ; Sang Hak LEE ; Myeng Gon KIM ; Se Joong RIM ; Do Yun LEE ; Won Heum SHIM
Korean Circulation Journal 1998;28(5):819-824
Coarctation of aorta is a rare cause of secondary hypertension, and premature death will occur if no appropriate treatment is given. The only effective treatment was surgery before 1980, but restenosis was frequent. Several works on percutaneous transluminal angioplasty of the disease were reported. In patients with previously operated recoarctation, there is no doubt that balloon angioplasty is now the first choice of the therapy because of the surgical risks of reoperation. Nevertheless, there has still been some controversy regarding the application of this therapy to native coarctation, because of the potential risk of aortic disruption and the high incidence of restenosis. There have been some clinical reports of successful stent implantation for coarctation without major complications since 1991. We report on our experience with balloon-expandable stent implantation for native coarctation of the aorta in a 23-year-old man with congenital mitral stenosis. Aortogram showed a coarcted aortic segment of 3 mm in diameter and 25 mm long just distal to the left subclavian artery. The peak systolic pressure gradient across the coarctation before stent implantation was 100 mmHg. Stent implantation was performed with 14 X 40 mm balloon with Palmaz P308 stent. The peak systolic pressure gradient decreased to zero and the diameter of the coarctation of aorta increased to 14 mm after stent implantation immediately. The patient tolerated well and no significant complications were encountered during the procedure.
Angioplasty
;
Angioplasty, Balloon
;
Aortic Coarctation*
;
Blood Pressure
;
Humans
;
Hypertension
;
Incidence
;
Mitral Valve Stenosis*
;
Mortality, Premature
;
Reoperation
;
Stents*
;
Subclavian Artery
;
Young Adult
5.A Case Report: Implantation of Balloon-Expandable Stent for Coarctation of the Aorta, Associated with Congenital Mitral Stenosis.
Seung Hyuk CHOI ; Sang Hak LEE ; Myeng Gon KIM ; Se Joong RIM ; Do Yun LEE ; Won Heum SHIM
Korean Circulation Journal 1998;28(5):819-824
Coarctation of aorta is a rare cause of secondary hypertension, and premature death will occur if no appropriate treatment is given. The only effective treatment was surgery before 1980, but restenosis was frequent. Several works on percutaneous transluminal angioplasty of the disease were reported. In patients with previously operated recoarctation, there is no doubt that balloon angioplasty is now the first choice of the therapy because of the surgical risks of reoperation. Nevertheless, there has still been some controversy regarding the application of this therapy to native coarctation, because of the potential risk of aortic disruption and the high incidence of restenosis. There have been some clinical reports of successful stent implantation for coarctation without major complications since 1991. We report on our experience with balloon-expandable stent implantation for native coarctation of the aorta in a 23-year-old man with congenital mitral stenosis. Aortogram showed a coarcted aortic segment of 3 mm in diameter and 25 mm long just distal to the left subclavian artery. The peak systolic pressure gradient across the coarctation before stent implantation was 100 mmHg. Stent implantation was performed with 14 X 40 mm balloon with Palmaz P308 stent. The peak systolic pressure gradient decreased to zero and the diameter of the coarctation of aorta increased to 14 mm after stent implantation immediately. The patient tolerated well and no significant complications were encountered during the procedure.
Angioplasty
;
Angioplasty, Balloon
;
Aortic Coarctation*
;
Blood Pressure
;
Humans
;
Hypertension
;
Incidence
;
Mitral Valve Stenosis*
;
Mortality, Premature
;
Reoperation
;
Stents*
;
Subclavian Artery
;
Young Adult
6.A Case of Cysticercosis in the Scrotum.
Ha Sung RIM ; Min Eui KIM ; Jong Hak LEE ; Dae Soo CHANG
Korean Journal of Urology 1982;23(5):721-722
Cysticercosis is a parasitic disease which results when man serves as the intermediate host of Taenia Solium, the pork tape warm; the larvae, cysticercus, develop in various body tissue. We have recently experienced a case of cysticercosis in the scrotum diagnosed by excision & biopsy.
Biopsy
;
Cysticercosis*
;
Cysticercus
;
Larva
;
Parasitic Diseases
;
Scrotum*
;
Taenia solium
7.Intraparenchymal Pericatheter Cyst as a Complication of a Ventriculo-Peritoneal Shunt in a Premature Infant.
Hae Ri RIM ; Sung Kyoo HWANG ; Soon Hak KWON ; Heng Mi KIM
Journal of Korean Neurosurgical Society 2011;50(2):143-146
A ventriculo-peritoneal shunt is a standard surgical management for hydrocephalus, but complications may impede the management of this disease. Obstruction of the catheter is one of the most common complications and manifests clinically in various ways. Intraparenchymal cyst development after shunt malfunction has been reported by several authors, but the underlying mechanism and optimal treatment methods are debatable. The authors report a case of intraparenchymal cyst formation around a proximal catheter in a premature infant after a ventriculo-peritoneal shunt and discuss its pathogenesis and management.
Catheters
;
Humans
;
Hydrocephalus
;
Infant, Newborn
;
Infant, Premature
;
Ventriculoperitoneal Shunt
8.Analysis of the Factors that Influence the Range of Motion after Total Knee Arthroplasty.
Yong Hoon KIM ; Keun Woo KIM ; Hak Jin MIN ; Ui Seoung YOON ; Kook Heoung CHO ; Dae Young KIM ; Sang Rim KIM
Journal of the Korean Knee Society 1999;11(1):20-25
A satisfactory range of motion is one of the important goal of total knee arthroplasty. We investigated the factors that may influence the range of motion after total knee arthroplasty in 49 arthroplasties of 36 patients with minimum follow-up of 12 months. For minimizing the effect of other variables we included only osteoarthritic patients who received primary AGC(BIOMET) knees, cemented fixation of all three component by one surgeon. Some factors that may affect final results were verified. These factors include BMI(ratio of weight and height), preoperative range of motion, preoperative X-ray findings such as sever- ity of spur change and varus deformity, early continuous passive motion trial. Statistical analysis was done by Students t test. The statistically significant factors which influenced the range of motion after arthroplasty were the preoperative flexion deformity and range of flexion, varus deformity, and spur change.
Arthroplasty*
;
Congenital Abnormalities
;
Follow-Up Studies
;
Humans
;
Knee*
;
Range of Motion, Articular*
9.Possible Effects of Radiofrequency Electromagnetic Field Exposure on Central Nerve System
Ju Hwan KIM ; Jin Koo LEE ; Hyung Gun KIM ; Kyu Bong KIM ; Hak Rim KIM
Biomolecules & Therapeutics 2019;27(3):265-275
Technological advances of mankind, through the development of electrical and communication technologies, have resulted in the exposure to artificial electromagnetic fields (EMF). Technological growth is expected to continue; as such, the amount of EMF exposure will continue to increase steadily. In particular, the use-time of smart phones, that have become a necessity for modern people, is steadily increasing. Social concerns and interest in the impact on the cranial nervous system are increased when considering the area where the mobile phone is used. However, before discussing possible effects of radiofrequency-electromagnetic field (RF-EMF) on the human body, several factors must be investigated about the influence of EMFs at the level of research using in vitro or animal models. Scientific studies on the mechanism of biological effects are also required. It has been found that RF-EMF can induce changes in central nervous system nerve cells, including neuronal cell apoptosis, changes in the function of the nerve myelin and ion channels; furthermore, RF-EMF act as a stress source in living creatures. The possible biological effects of RF-EMF exposure have not yet been proven, and there are insufficient data on biological hazards to provide a clear answer to possible health risks. Therefore, it is necessary to study the biological response to RF-EMF in consideration of the comprehensive exposure with regard to the use of various devices by individuals. In this review, we summarize the possible biological effects of RF-EMF exposure.
Apoptosis
;
Brain
;
Cell Phones
;
Central Nervous System
;
Electromagnetic Fields
;
Human Body
;
In Vitro Techniques
;
Ion Channels
;
Magnets
;
Models, Animal
;
Myelin Sheath
;
Nervous System
;
Neurons
;
Smartphone
10.Exposure to 835 MHz RF-EMF decreases the expression of calcium channels, inhibits apoptosis, but induces autophagy in the mouse hippocampus.
Ju Hwan KIM ; Uy Dong SOHN ; Hyung Gun KIM ; Hak Rim KIM
The Korean Journal of Physiology and Pharmacology 2018;22(3):277-289
The exponential increase in the use of mobile communication has triggered public concerns about the potential adverse effects of radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones on the central nervous system (CNS). In this study, we explored the relationship between calcium channels and apoptosis or autophagy in the hippocampus of C57BL/6 mice after RF-EMF exposure with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Firstly, the expression level of voltage-gated calcium channels (VGCCs), a key regulator of the entry of calcium ions into the cell, was confirmed by immunoblots. We investigated and confirmed that pan-calcium channel expression in hippocampal neurons were significantly decreased after exposure to RF-EMF. With the observed accumulation of autolysosomes in hippocampal neurons via TEM, the expressions of autophagy-related genes and proteins (e.g., LC3B-II) had significantly increased. However, down-regulation of the apoptotic pathway may contribute to the decrease in calcium channel expression, and thus lower levels of calcium in hippocampal neurons. These results suggested that exposure of RF-EMF could alter intracellular calcium homeostasis by decreasing calcium channel expression in the hippocampus; presumably by activating the autophagy pathway, while inhibiting apoptotic regulation as an adaptation process for 835 MHz RF-EMF exposure.
Absorption
;
Animals
;
Apoptosis*
;
Autophagy*
;
Calcium Channels*
;
Calcium*
;
Cell Phones
;
Central Nervous System
;
Down-Regulation
;
Electromagnetic Fields
;
Hippocampus*
;
Homeostasis
;
Ions
;
Mice*
;
Neurons