CHOP deficiency inhibits methylglyoxal-induced endothelial dysfunction

Choi, Yoon Young,Kim, Suji,Han, Jung-Hwa,Nam, Dae-Hwan,Park, Kwon Moo,Kim, Seong Yong,Woo, Chang-Hoon Elsevier 2016 Biochemical and biophysical research communication Vol.480 No.3

<P><B>Abstract</B></P> <P>Epidemiological studies suggested that diabetic patients are susceptible to develop cardiovascular complications along with having endothelial dysfunction. It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction rather than glucose itself. Here, we investigated the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress. Biochemical data showed that 4-PBA significantly inhibited MGO-induced protein cleavages of PARP-1 and caspase-3. In addition, it was found that high glucose-induced endothelial apoptosis was enhanced in the presence of GLO1 inhibitor, suggesting the role of endogenous MGO in high glucose-induced endothelial dysfunction. MGO-induced endothelial apoptosis was significantly diminished by the depletion of CHOP with si-RNA against human <I>CHOP</I>, but not by SP600125, a specific inhibitor of JNK. The physiological relevance of this signaling pathway was demonstrated in CHOP deficiency mouse model, in which instillation of osmotic pump containing MGO led to aortic endothelial dysfunction. Notably, the aortic endothelial dysfunction response to MGO infusion was significantly improved in CHOP deficiency mice compared to littermate control. Taken together, these findings indicate that MGO specifically induces endothelial dysfunction in a CHOP-dependent manner, suggesting the therapeutic potential of CHOP inhibition in diabetic cardiovascular complications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We examine the role of ER stress in MGO-induced endothelial apoptosis. </LI> <LI> TUDCA and CHOP depletion inhibits MGO-induced endothelial apoptosis. </LI> <LI> CHOP deficiency ameliorates MGO-induced aortic endothelial dysfunction in vivo. </LI> <LI> CHOP deficiency inhibits MGO-induced endothelial apoptosis in vivo. </LI> </UL> </P>

Sun Ginseng Protects Endothelial Progenitor Cells From Senescence Associated Apoptosis

임우석,정진영,반재준,임지연,이순태,주건,김만호 고려인삼학회 2012 Journal of Ginseng Research Vol.36 No.1

Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG),which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verifi ed that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fl uorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms. Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside Rg3 prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG),which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by β-galactosidase (β-gal) staining. Staining with 4′-6-Diamidino-2-phenylindole verifi ed that most adherent cells (93±2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of β-gal-positive EPCs was decreased from 93.8±2.0% to 62.5±3.6% by SG treatment. A fl uorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms.

Effect of Scutellariae Radix Extract on the High Glucose-Induced Apoptosis in Cultured Vascular Endothelial Cells

SUH, Kwang Sik,NAM, Yeon Ho,AHN, Young Min,KIM, Nam Jae,PARK, Cheol Young,KOH, Gwanpyo,OH, Seungjoon,WOO, Jeong Taek,KIM, Sung Woon,KIM, Jin Woo,KIM, Young Seol WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Endothelial cell apoptosis has been postulated as the initial trigger of the progression of progression disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [(3)^H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial tell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling(TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7mM) for 72h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.

Galpha12 Protects Vascular Endothelial Cells from Serum Withdrawal-Induced Apoptosis through Regulation of miR-155

이현정,이은직,서미란 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.1

Purpose: Apoptosis of vascular endothelial cells is a type of endothelial damage that is associated with the pathogenesis of cardiovasculardiseases such as atherosclerosis. Heterotrimeric GTP-binding proteins (G proteins), including the alpha 12 subunit ofG protein (Gα12), have been found to modulate cellular proliferation, differentiation, and apoptosis of numerous cell types. However,the role of Gα12 in the regulation of apoptosis of vascular cells has not been elucidated. We investigated the role of Gα12 inserum withdrawal-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its underlying mechanisms. Materials and Methods: HUVECs were transfected with Gα12 small-interfering RNA (siRNA) to knockdown the endogenousGα12 expression and were serum-deprived for 6 h to induce apoptosis. The apoptosis of HUVECs were assessed by Western blottingand terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of microRNAs were analyzedby quantitative real-time PCR. Results: Knockdown of Gα12 with siRNA augmented the serum withdrawal-induced apoptosis of HUVECs and markedly repressedthe expression of microRNA-155 (miR-155). Serum withdrawal-induced apoptosis of HUVECs was inhibited by the overexpressionof miR-155 and increased significantly due to the inhibition of miR-155. Notably, the elevation of miR-155 expressionprevented increased apoptosis of Gα12-deficient HUVECs. Conclusion: From these results, we conclude that Gα12 protects HUVECs from serum withdrawal-induced apoptosis by retainingmiR-155 expression. This suggests that Gα12 might play a protective role in vascular endothelial cells by regulating the expressionof microRNAs.

제대정맥 내피세포에서 Amiloride 유도체에 의한 Apoptosis 반복

박규창,박규상,문수지,Park, Kyu Chang,Park, Kyu Sang,Moon, Soo Jee 대한소아청소년과학회 2003 Clinical and Experimental Pediatrics (CEP) Vol.46 No.1

Purpose : Human umbilical vein endothelial cells(HUVECs) play an important role in regulating blood flow by releasing vasoactive substances. It has been reported that endothelial impairment and dysfunction might be a primary cause of placental vascular disease, which is manifested clinically as preeclampsia in mother and intrauterine growth restriction in fetus. Furthermore, the frequency of apoptotic changes is increased in umbilical and placental tissues from growth-restricted pregnancies. However, the various mechanisms of umbilical endothelial cell apoptosis have not been broadly proposed. We investigate the effects of amiloride derivatives on apoptotic death of HUVECs and identify their ionic mechanism. Methods : HUVECs were purchased from Clonetics, and cultured on endothelial cell growth medium. MTT assay and flow cytometry were used for assessing cytotoxic effect and confirming the apoptosis. Changes in intracellular ion concentrations were measured with specific fluorescent dyes and fluorescence imaging analysis system. Results : Amiloride derivatives elicited cytotoxic effects on HUVECs with dose-dependent manners and the rank order of potency is HMA($IC_{50}\;11.2{\mu}M$), MIA>EIPA>>amiloride. HMA-induced cytotoxicity is dependent on extra- and intracellular pH, that is, increase extra- and intracellular pH augmented the cytotoxic effects of HMA. HMA dose-dependently reduced intracellular major ions, such as $K^+$ and $Cl^-$. Interestingly, the depletion of intracellular ions induced by HMA was also significantly enhanced at alkaline extracellular pH. Conclusion : Amiloride derivatives induce apoptosis of HUVECs with dose and pH dependent manners. They reduce intracellular $K^+$ and $Cl^-$ concentration, which is also extracellular pH dependent. 목 적 : 제대정맥은 모체의 혈액을 태아로 운반하여 산소와 영양물질을 공급하는 유일한 통로이다. 이러한 제대 혈류의 장애가 있을 시 자궁내 성장제한, 임신성 고혈압 등을 초래할 수 있다. 제대-태반 혈관의 내피세포 손상을 유발하는 원인 중 amiloride 유도체들을 중심으로 내피세포에 미치는 amiloride 유도체들의 작용을 밝히고, 세포 내 이온농도 변화와 apoptosis 간의 관계를 규명하고자 하였다. 방 법 : 인간 제대정맥 내피세포는 Clonetics로부터 구입하였으며, 내피세포 성장에 필요한 여러 성장인자가 포함된 배지에서 배양하였다. MTT 방법과 flow cytometry 방법을 이용하여 세포독성 효과 및 apoptosis를 확인하였다. 세포 내 이온농도 변화를 측정하기 위해서는 각각의 목적에 적합한 형광염료들을 세포 내에 부하시켜 놓은 뒤, 형광 현미경과 연결된 영상분석장치를 이용하여 관찰하였다. 결 과 : 1) Amiloride 유도체들은 농도 의존적으로 HUVEC의 사멸을 나타내었으며, 각각의 정도는 HMA($IC_{50}$; $11.2{\mu}M$), MIA($13.6{\mu}M$)>EIPA($30.8{\mu}M$)>>amiloride($106{\mu}M$) 순이었다. 2) 세포주기 분석결과 apoptosis의 특징적인 sub $G_0/G_1$ ploidy peak를 나타냈으며, 이러한 작용은 caspase 억제제에 의해 감소되었다. 3) Annexin-V와 propidium iodide 이중 염색 결과 apoptosis로 진행된 세포의 비율(73.0%)을 대조군(11.3%)에 비해 현저히 증가시켰다. 4) HMA에 의한 apoptosis 효과는 세포외액의 pH를 높이거나, $NH_4Cl$을 투여하여 세포내액의 pH를 높일 경우 크게 증가하였다. 5) HMA는 농도 의존적으로 세포내 주요 이온인 $K^+$ 및 $Cl^-$의 세포내 농도를 감소시켰으며, 이러한 효과 역시 세포외액의 pH를 높일수록 현저하게 증가하였다. 결 론 : 이상의 결과들로 미루어 볼 때, HUVEC에서 amiloride 유도체들에 의한 apoptosis 과정에 세포내 주요 이온 농도 감소가 일부 관여하고 있을 것이라 생각된다.

STAT3 phosphorylation at Tyr705 affects DRP1 (dynamin-related protein 1) controlled-mitochondrial fission during the development of apoptotic-resistance in pulmonary arterial endothelial cells

Zhang Han,Chen Li,Li Jiachen,Sun Jiashu,Zhao Qixu,Wang Sheng,Li Gang 한국유전학회 2024 Genes & Genomics Vol.46 No.7

Background The apoptosis-resistant pulmonary arterial endothelial cells (PAECs) are known to be major players in the pulmonary remodeling of pulmonary arterial hypertension (PAH) and exhibit an abnormal metabolic profile with mitochondrial dysfunction. Mitochondrial fission has been shown to regulate the apoptosis of several cell types, but this is largely unexplored in the PAECs. Objective The roles of mitochondrial fission control by Dynamin related protein-1 (DRP1) in the development of PAECs apoptosis suppression were investigated in present study and the potential mechanisms behind this were furtherly explored. Methods The mitochondrial morphology was investigated in PAECs from PAH rats with the pulmonary plexiform lesions, and the relations of it with DRP1 expression and apoptosis were furtherly identified in apoptosis-resistant PAECs induced by hypoxia. PAECs were isolated from rats with severe PAH and from normal subjects, the apoptotic-resistant PAECs were induced by hypoxia. DRP1 gene knockdown was achieved via DRP1-siRNA, DRP1 and STAT3 phosphorylation were blocked using its inhibitors, respectively. Apoptosis was analyzed by flow cytometry, and mitochondrial morphology was investigated by transmission electron microscope and confocal microscopy. Results The PAECs isolated from PAH rats with the pulmonary plexiform-like lesions and displayed lower apoptotic rate with increased DRP1 expression and mitochondrial fragmentation. In addition, similar observations were achieved in apoptosis-resistant PAECs induced by hypoxia. Targeting DRP1 using siRNA and pharmacologic blockade prevented the mitochondrial fission and subsequent apoptotic resistance in PAECs under hypoxia. Mechanistically, STAT3 phosphorylation at Tyr705 was shown to be activated in both PAH and hypoxia-treated PAECs, leading to the regulation of DRP1 expression. Of importance, targeting STAT3Tyr705 phosphorylation prevented DRP1 disruption on apoptosis in PAECs under hypoxia. Conclusions These data indicated that STAT3 phosphorylation at Tyr705 impacted DRP1-controlled mitochondrial fission during the development of apoptosis-resistance in PAECs, suggesting mitochondrial dynamics may represent a therapeutic target for PAH. Background The apoptosis-resistant pulmonary arterial endothelial cells (PAECs) are known to be major players in the pulmonary remodeling of pulmonary arterial hypertension (PAH) and exhibit an abnormal metabolic profile with mitochondrial dysfunction. Mitochondrial fission has been shown to regulate the apoptosis of several cell types, but this is largely unexplored in the PAECs. Objective The roles of mitochondrial fission control by Dynamin related protein-1 (DRP1) in the development of PAECs apoptosis suppression were investigated in present study and the potential mechanisms behind this were furtherly explored. Methods The mitochondrial morphology was investigated in PAECs from PAH rats with the pulmonary plexiform lesions, and the relations of it with DRP1 expression and apoptosis were furtherly identified in apoptosis-resistant PAECs induced by hypoxia. PAECs were isolated from rats with severe PAH and from normal subjects, the apoptotic-resistant PAECs were induced by hypoxia. DRP1 gene knockdown was achieved via DRP1-siRNA, DRP1 and STAT3 phosphorylation were blocked using its inhibitors, respectively. Apoptosis was analyzed by flow cytometry, and mitochondrial morphology was investigated by transmission electron microscope and confocal microscopy. Results The PAECs isolated from PAH rats with the pulmonary plexiform-like lesions and displayed lower apoptotic rate with increased DRP1 expression and mitochondrial fragmentation. In addition, similar observations were achieved in apoptosis-resistant PAECs induced by hypoxia. Targeting DRP1 using siRNA and pharmacologic blockade prevented the mitochondrial fission and subsequent apoptotic resistance in PAECs under hypoxia. Mechanistically, STAT3 phosphorylation at Tyr705 was shown to be activated in both PAH and hypoxia-treated PAECs, leading to the regulation of DRP1 expression. Of importance, targeting STAT3Tyr705 phosphorylation prevented DRP1 disruption on apoptosis in PAECs under hypoxia. Conclusions These data indicated that STAT3 phosphorylation at Tyr705 impacted DRP1-controlled mitochondrial fission during the development of apoptosis-resistance in PAECs, suggesting mitochondrial dynamics may represent a therapeutic target for PAH.

소의 대동맥 내피세포에서 산화저밀도 지단백에 의한 아포프토시스에 백일해 독소 및 콜레라 독소가 미치는 영향

손호영(Ho Young Son),강성구(Sung Ku Kang),강무일(Moo Il Kang),차봉연(Bong Youn Cha),이광우(Kwang Woo Lee),장상아(Sang Ah Chang),최윤희(Yoon Hee Choi),문성대(Sung Dae Moon),안유배(Yoo Bae Ahn),손현식(Hyun Sik Son),윤건호(Kun Ho Yoon) 대한내과학회 1999 대한내과학회지 Vol.56 No.5

Objectives : Oxidized LDL is thought to play a key role in atherogenesis. Among their wide variety of biological properties, oxidized LDL injures the endothelium as an early event of atherogenesis. However, the mechanisms by which oxidized LDL injures endothelial cells are not definitely known. In order to evaluate the involvement of GTP-binding protein on the mechanism of apoptosis, we studied the effects of pertussis and cholera toxin on oxidized LDL-induced apoptosis in bovine aortic endothelial cells(BAECs). Methods : Oxidized LDL elicited apoptosis in cultured BAECs as shown by characteristic morphological and biochemical changes. Chromatin condensation and nucleus fragmentation were visualized by using fluorescence microscopy of intact cells staining by acridine orange/ ethidium bromide. DNA fragmentation was quantified by an ELISA with specific antibody for bromodeoxyuridine- labelled DNA fragments and confirmed with DNA ladder formation. Results : Studies using a combination of bacterial toxins which change the function of GTP-binding protein suggest that oxidized LDL-induced apoptosis was regulated by GTP-binding protein. Oxidized LDL-induced apoptosis was not changed by pretreatment of BAECs with pertussis toxin. In contrast, pretreatment with cholera toxin completely prevented the oxidized LDL- induced apoptosis. Conclusion : These results show that oxidized LDL induces apoptosis of BAECs and suggest that cholera toxin-sensitive G-proteins are involved in signal transduction of oxidized LDL-induced apoptosis of BAEC.

혈관내피세포에서 c-Jun N-terminal kinase에 의해 조절되는 세포사멸에 고농도의 피노실빈이 미치는 효과

송지나(Jina Song),박진선(Jinsun Park),정은실(Eunsil Jeong),소아영(A-Young So),피재호(Jaeho Pyee),박헌용(Heonyong Park) 한국생명과학회 2015 생명과학회지 Vol.25 No.4

피노실빈은 소나무 등에서 흔히 관찰되는 스틸벤노이드이다. 혈관내피세포에서 ~pM에서 ~nM 정도의 낮은 농도의 피노실빈은 세포성장, 세포이동, 항염증반응을 유도한다. 그러나 최근에 고농도의 피노실빈이 소 대동맥 내피세포의 세포사를 유발하고 있음이 보고되었으나, 그 자세한 기전이나 경로 연구가 미흡하여 이번 연구에서 고농도 피노실빈의 세포사 유발 경로를 규명하기 위한 실험을 수행하였다. 고농도의 피노실빈은 caspase-3 절단, 포스파티딜 세린의 플립플롭, 핵 분절 등을 유도하는 것으로 보아 세포사멸을 통한 세포사를 유발함을 알았다. 또한 혈청기아나 100 μM etoposide에 의하여 촉발하는 caspase-3 활성/핵분절이 추가적으로 증가하는 현상이 관찰되었다. 이는 피노실빈이 일으키는 세포사멸은 혈청기아나 etoposide에 의해 일어나는 세포사멸과는 다른 경로로 진행됨을 의미하므로 고농도의 피노실빈에 의해 촉발되는 세포신호전달을 탐색한 결과, JNK와 eNOS가 관여함을 알았다. 두 신호전달 물질 중에 어느 것이 피노실빈 유도 세포사에 중요한 지를 알기 위한 추가적인 실험을 진행하였다. 그 결과, JNK 억제자인 SP-600125는 피노실빈에 의한 세포사멸을 억제하였으나, eNOS 억제자인 L-NAME은 아무런 영향이 없는 것으로 보아 JNK가 피노실빈에 의해 유발되는 세포사멸에 관여하는 세포신호 전달물질임을 알았다. Pinosylvin is a stilbenoid found in the Pinus species. Pinosylvin at ~pM to ~nM concentrations induces cell proliferation, cell migration and anti-inflammatory activity in endothelial cells. However, it was recently reported that pinosylvin at high concentrations (50 to 100 μM) induces cell death in bovine aortic endothelial cells. In this study, we conducted a series of experiments to discover how pinosylvin at a high concentration (50 μM) induces endothelial cell death. Pinosylvin at the high concentration was shown to induce endothelial cell apoptosis through enhancing caspase-3 activity, flip-flop of phosphatidyl serine, and nuclear fragmentation. We found that pinosylvin at the high concentration additively increased caspase-3 activity enhanced by serum-starvation or treatment with 100 μM etoposide. We also determined that pinosylvin at the high concentration promoted activations of c-Jun N-terminal kinase (JNK) and endothelial nitric oxide synthetase (eNOS). We further ran a series of experiments to find out which signaling molecule plays a critical role in the pinosylvin-induced apoptosis. We finally found that SP-600125, a JNK inhibitor, had an inhibitory effect on the pinosylvin-induced endothelial cell death, but L-NAME, an eNOS inhibitor, had no effect. These data indicate that JNK is involved in the pinosylvin-induced apoptosis. Collectively, pinosylvin at high doses induces cell apoptosis via JNK activation.

Hypoxanthine causes endothelial dysfunction through oxidative stress-induced apoptosis

Kim, You-Jin,Ryu, Hye-Myung,Choi, Ji-Young,Cho, Jang-Hee,Kim, Chan-Duck,Park, Sun-Hee,Kim, Yong-Lim Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS) are implicated in the pathogenesis of vascular diseases. ROS are generated and hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are associated with an increased level of hypoxanthine. We aimed to study the direct role of hypoxanthine in endothelial dysfunction in human umbilical vascular endothelial cells (HUVECs). Hypoxanthine induced cell death and production of ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein expression related to apoptosis. When cells were pretreated with <I>N</I>-acetylcysteine or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk and <I>N</I>-acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the ROS production and caspase pathway. Thus, an increased extracellular concentration of hypoxanthine induces endothelial dysfunction through ROS production and regulates expression of apoptosis-related proteins in HUVECs. These effects are expected to be associated with some vascular diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Hypoxanthine induced H<SUB>2</SUB>O<SUB>2</SUB> production in endothelial cells. </LI> <LI> Hypoxanthine induced ROS-related apoptosis in HUVECs. </LI> <LI> Hypoxanthine promoted endothelial dysfunction via a mechanism involving the caspase-3. </LI> </UL> </P>

방사선 조영제로 유발된 Apoptosis에 의한 혈관내피세포 손상

이식,김상균,정수진,이상연,성미정,문상옥,김원,박성광 대한혈관외과학회 2004 Vascular Specialist International Vol.20 No.1