Role of the Peripheral Vestibular End Organ in the Expression of c-Fos Protein in the Medial Vestibular Nucleus Following Occlusion of the Anterior Inferior Cerebellar Artery

김나리,이재희,최명애,박병건,김민선,박병림 대한평형의학회 2012 Research in Vestibular Science Vol.11 No.2

Background and Objectives: The present study investigated the role of the peripheral vestibular end organ in vestibular symptoms and temporal changes in expression of c-Fos protein in the vestibular nuclei following anterior inferior cerebellar artery (AICA) occlusion using rats with unilateral or bilateral labyrinthectomy. Materials and Methods: Expression of c-Fos protein in the vestibular nuclei was measured 2,12, 24, and 48 hours after AICA occlusion. Results: Unilateral AICA occlusion significantly induced expression of c-Fos protein bilaterally in the medial, inferior,superior, and lateral vestibular nuclei. Following AICA occlusion, the medial vestibular nucleus (MVN) showed the highest expression of c-Fos protein among the 4 vestibular nuclei. The expression of c-Fos protein was asymmetric between the bilateral MVN, showing higher expression in the MVN contralateral to the side of AICA occlusion compared to the ipsilateral MVN. The degree of asymmetry in c-Fos protein expression between the bilateral MVN peaked 12 hours after AICA occlusion. The expression of c-Fos protein gradually decreased 24 hours after AICA occlusion and returned to control levels 48 hours after AICA occlusion. Unilateral labyrinthectomy significantly decreased expression of c-Fos protein in the MVN ipsilateral to the side of labyrinthectomy following AICA occlusion. Moreover,bilateral labyrinthectomy significantly decreased expression of c-Fos protein in the bilateral MVN flowing AICA occlusion. Conclusion: These results suggest that afferent signals from the peripheral vestibular end organ are crucial to the expression of c-Fos protein in the MVN following AICA occlusion and that expression of c-Fos protein is sustained for 24 hours after AICA occlusion.

자궁내막선암의 세포주인 HEC-1-A에서 표피성장인자가 c-fos mRNA proto-oncogene 발현에 미치는 영향

박지영(JY Park),박용균(YK Park),강재성(JS Kang) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.4

Growth factors stimulate cell proliferation and differentiation through binding to specific high affinity receptors. Signalling pathway that mediate the normal functions of growth factors are commonly subverted in cancers. Proto-oncogenes are normal cellular genes whose alteration by mutation or deregulation has been implicated in the process of tumorigenesis and they play a role for control of normal cellular growth and differentiation. Epidermal growth factor is mitogenic in moderately differentiated endometrial adenocarcinoma cell line, HEC-1-A. These studies were performed to determine the effects of EGF on c-fos mRNA proto-oncogene expression, and whether EGF need new protein synthesis, and whether PKC pathway plays a role in the induction of c-fos mRNA expression in EGF treated cells. HEC-1-A cells were grown to confluency and maintained in a serum free media (0.3% BSA) 24 hours prior to treatment. The cells were treated with EGF (0, 0.01, 0.1, 1.0, 10, 100 ng/ml) and PMA (0, 0.001, 0.01, 0.1, 1, 10, 100 1000 nM) at varying times (0, 0.12, 0.25, 0.5, 1, 3, 6, 12, 24 h) and the expression of c-fos mRNA expression examined by northern blot analysis. The expession of c-fos mRNA induced by EGF and PMA was dose dependent and peak induction occurred at 1 hour, and decreased steadily after 1 hour. To determine whether PKC may mediate EGF effects on c-fos mRNA expression, the cells were preincubated without or with PMA (1000 nM) for 48 hours for down regulation of PKC, followed by EGF (100 ng/ml). Following 48 hours preincubation with PMA (1000 nM), EGF increased c-fos mRNA expression, while PMA failed to induce its expression, suggesting that EGF induces c-fos mRNA expression independent of PKC activation. To determine whether EGF need new protein synthesis in the induction of c-fos mRNA, the cells were preincubated with anisomycin, a stringent protein synthesis inhibitor, for 30 minutes followed by EGF(100 ng/ml). Anisomycin induced c-fos mRNA and augmented EGF effects on c-fos mRNA expression. These results suggest that EGF may induce c-fos mRNA expression through PKC independent pathway and the induction does not require new protein synthesis.

동대동맥동신경 제거 흰쥐에서 혈압조절에 대한 전정기관의 역할

조상곤,이재효,김민선,김원철,박병림,오석규,정진원 대한순환기학회 2003 Korean Circulation Journal Vol.33 No.6

L1210 암세포에서 Multidrug Resistance-associated Protein(MRP),c-myc 및 c-fos 유전자의 발현양상

김성용 영남대학교 의과대학 1997 Yeungnam University Journal of Medicine Vol.14 No.1

항암제에 대한 내성은 내인성 또는 획득한 내성 모두가 암의 치료에 장애가 된다. P-당단백질을 encode 하고있는 mdrl 유전자의 발현이 항암제에 대해 내성을 가지고 있는 암세포에서 많이 관찰되고 있으며, 최근에는 시험관적으로 항암제에 대한 내성이 유도된 암세포주들에서 mdrl 유전자가 발현되지 않는 암세포들이 보고되고 있다. 다제내성에 관계하는 또 하나의 유전자인 MRP 발현정도를 L1210세포와 내성인 L1210변이주들에서 조사하였으며, c-myc과 c-fos 유전자의 발현변화를 관찰하였다. RT-PCR을 시행하여 L1210, L1210AdR, L1210VcR에서 MRP 유전자 발현을 확인하였으며, Northern hybridization 한 결과 L1210세포에 비하여 L1210AdR은 유전자 발현이 40% 정도 감소하였으며, L1210Cis는 90% 정도의 유전자 발현감소가 관찰되었다. c-myc과 c-fos유전자의 Northern hybridization 한 결과 L1210에 비하여 L1210AdR은 발현감소가 나타났으나, L1210VcR과 L1210Cis의 경우는 오히려 발현증가가 관찰되었다. The occurrence of multidurg resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. In this study the gene expressions of multidrug resistance-associated protein (MRP), c-myc and c-fos were investigated in L1210 cells. Adriamucin- or vincristine-resistant L1210 cells, L1210AdR or L1210VcR, respectively, has been indentiified to overexpression of mdrl gene. The expression leve of MRP gene in L1210AdR and L1210Cis was more decreased than that in L1210 cells. The c-myc and c-fos gnens were expressed boty in L1210 and resistant subines. In L1210AdR, the expressions level of c-myc and c-fos genes were decreased than in L1210. However, in L1210VcR and L1210Cis, c-myc and c-fosgene expressionwere rather increased than L1210. There results suggested that MRP does not contribute in resistance of drug-resistant L1210 cells and there is no relations between MRP and mdrl gene expression. The expression of c-myc and c-fos gene may be changed during transformation of L1210 to drug-resistant sublines.

Increased c-Fos Expression Contributes to Cell Survival Enhanced by Stromal Cell Derived Factor-1/CXCL12 in Synergy with other Cytokines in Mo7e Cells

( Ae Ran Lee ),( Jeong A Park ),( Young Eun Kim ),( Hyung Joo Kwon ),( Young Hee Lee ) 한국조직공학·재생의학회 2009 조직공학과 재생의학 Vol.6 No.14

Stromal cell-derived factor-1 (SDF-1/CXCL12) enhances the survival of hematopoietic stem cells, progenitor cells, and a human progenitor cell line MO7e, especially in synergy with other cytokines. Previously, we reported that c-Fos was synergistically induced by combined stimulation with SDF-1/CXCL12 plus other cytokines. Here, we aimed to evaluate that induced c-Fos expression is required for the survival enhancement in MO7e cells. First by using RNase protection assay, we confirmed that synergistic induction of c-Fos was unique among several stress-related genes. Since c-Fos is known as one of the components of transcription factor AP-1, we performed electrophoretic mobility shift assay. The DNA binding activity of AP-1 was also synergistically enhanced by combined stimulation, and c-Fos was identified in the DNA bound complex. To further evaluate the significance of c-Fos expression for survival of MO7e cells, we employed cell permeable c-Fos dominant negative mutant form (A-Fos-MTS) and protein transduction procedure. Inhibition of c-Fos by treatment with A-Fos-MTS significantly reduced survival of MO7e cells in the presence of SDF-1/CXCL12 plus low concentration of GM-CSF. Therefore, we suggest that induction of c-Fos and enhanced AP-1 activity contribute to survival effect of cytokines in MO7e cells.

흰쥐 해마에서 수영운동이 c-fos, c-jun 발현에 미치는 영향

이성호(Sung-Ho Lee) 한국콘텐츠학회 2011 한국콘텐츠학회논문지 Vol.11 No.1

본 연구는 흰쥐 해마에서 c-fos, c-jun 발현에 수영운동이 미치는 영향을 규명하는 것이다. 실험 대상은 생후 4주 흰쥐(4-weeks aged rat)와 생후 4개월 흰쥐(16-weeks aged rat)를 사용하였다. 두 집단 모두 대조군, 실험군으로 분류하였으며, 수영 운동은 1일 1시간 하였으며 1, 3, 7일 실시한 후 다음과 같은 결과를 얻을 수 있었다. c-fos, c-jun 단백질 발현에 있어서 두 실험군 모두 운동 1, 3, 7일에서 유의하게 증가하였으며, 7일이 가장 많이 증가하였고 3일, 1일 순으로 증가 하였다. 두 실험군을 비교했을 때 생후 4주 그룹이 4개월 그룹보다 더 많은 c-fos, c-jun 단백질 발현을 보여 통계적으로 유의하게 나타났다. 따라서 수영 운동이 해마에서 c-fos, c-jun 단백질 발현을 증가시키는 것으로 나타나 운동의 효과가 있는 것으로 보이며, 수영 운동에 의한 초기발현 유전자의 활성화로 인하여 학습 및 기억과 같은 인식기능을 예방 및 개선시키며 신경성장 및 회복에 긍정적인 효과가 있는 것으로 보인다. This study is to examine the effect of swimming exercise on the expression of c-fos, c-jun protein in rat hippocampus. 4-weeks aged rats and 16-weeks aged rats were used in experimental materials. All of two groups were classified into control and swimming exercise group. Swimming exercise was practiced for an hour a day. The results were got as follows after practical application in 1 day, 3days, 7 days. The expression of c-fos, c-jun protein was increased in all of the two experimental groups significantly in 1 day, 3days, 7 days. It was increased gradually in order of after 1 day, 3days, 7 days. There seems to be the effect of swimming exercise increasing the expression of c-fos, c-jun protein in hippocampus. Therefore swimming exercise can improve cognitive function such as learning and memory and prevent through activating immediate - early gene by swimming exercise. And it seems to have the positive effect on growth and recovery of nerve.

단일 전기경련충격에 의한 흰쥐 변연계의 Fos 발현의 증가

이성필 大韓神經精神醫學會 1996 신경정신의학 Vol.35 No.1

저자들은 아직까지 명확히 밝혀지지 않은 ECS의 대뇌 해부학적 작용부위를 알아 보기위하여 흰쥐에 단일 전기경련충격을 가하고 면역세포화학법의 방법으로 시간에 경과에 따른 Fos 발현을 측정하여 전기경련충격과 연관된 기전을 추측해 보고자 본 연구를 하였다. 체중 200∼300g Sprague-Dawley종 수컷 흰쥐를 사용하여 ECS 후 시간의 경과에 따른 c-fos 단백질(Fos)발현의 차이를 보기 위하여 ECS 후 즉시, 30분 후, 1시간 후, 2시간 후, 4시간 후, 8시간 후, 24시간 후에 각각(n=6) 면역세포화학법의 방법으로 Fos 발현을 조사하였고 이를 대조군인 위충격군과 비교하여 다음과 같은 결과를 얻었다. 1) ECS군이 대조군에 비하여 Fos 발현세포가 유의한 증가를 보인 부위는 치상회(dentate gyrus), 해마(hippo-campus), 이상피질(pyriform cortex) 복내측 시상하부(ventromedial hypothalamus), 편도체(amygdala)였으며 이중 치상회에서 Fos 발현세포가 가장 많이 증가되어 있었다. 그러나 변연계 경련(limbic seizure)의 주작용 부위로 알려진 흑질(substantia nigra)에서는 ECS군과 대조군 모두 Fos발현세포가 관찰되지 않았다. 2) 시간에 경과에 따른 Fos의 발현의 차이를 조사하였을때 ECS군에서는 ECS후 1시간후에 최고치에 달하다가 ECS 8시간후에 기저치로 돌아왔다. 그러나 대조군인 위충격군에서는 시간의 경과에 따른 유의한 차이가 없었다. 이상의 결과에서 전기경련축격은 대뇌의 치상회, 해마, 편도체, 이상피질, 그리고 복내측 시상하부의 c-fos 발현을 증가시키며 전기경련충격의 치료효과는 상기 구조물을 통하여 나타난다고 생각된다. Objects : Although the electroconvulsive therapy has been widely used for the treatment for major psychiatric illnesses, its mechanism of action is not clearly understood, yet. And the researches concerning the mechanism of action of electroconvulsive shock (ECS) have been focussed mostly about the neurotransmitter and receptor. In recent years, however, an alternative approach using c-fos protein (Fos) is newly accepted among several researchers in an attempt to understand the mechanism of action of ECS. The fact that c-fos, a kind of immediate early gene, is expressed by various physiological and pharmacologic stimuli in central nervous system shed light on the possibility of using it as a marker for neuronal activity. This study was designed to investigate the possible anatomical locations related to the action of ECS by observing the expression of c-fos with immunocytochemistry. Methods : The author investigated the affected areas and time-course of ECS in rat brain using Fos immunohistochemistry. The 84 Sprague-Dawley strain rats were divided into two groups, as experimental and control ones. The emergences of c-fos were measured rightly, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours after ECS treatments. Results : From the experiment, the following results were obtained ; 1) Fos expression increased significantly in the dentate gyrus, hippocampus, pyriform cortex, ventromedial hypothalamus and amygdala of experinmental group than the control group. 2) Fos expression reached maximum 1 hour after the ECS treatment and returned to the background level in 8 hours in the experimental group. Conclusion : These results imply that the mechanism of action of ECS might be mediated through the various areas of the brain, largely at the limbic system and cerebral cortex. And it is notable that the substantial increase of Fos was observed in the limbic system, which is known to be closely related to affective illnesses.

허혈-재관류시에 골격근에서의 heat shock protein 및 c-fos 유전자 발현에 관한 연구

정윤규,유임주,정혜선,김현,서영석 대한해부학회 1995 Anatomy & Cell Biology Vol.28 No.2

후계(後谿), 위중(委中), 후계배위중(後谿配委中) 침자(鍼刺)가 백서(白鼠)의 신경병리성(神經病理性) 동통억제(疼痛抑制) 및 c-Fos 단백(蛋白) 발현(發顯)에 미치는 영향(影響)

정정희,윤대환,나창수,유충열,윤여충,조명래,Jung, Jung-hee,Yun, Dae-whan,Na, Chang-su,Ryu, Choong-ryul,Yun, Yeo-chung,Cho, Myung-rae 대한침구의학회 2004 대한침구의학회지 Vol.21 No.1

Objective: We have studied to know effects of acupuncture at SI3, BL40, SI3 BL40 on mechnical allodynia, cold allodynia and c-fos protein expression in a model of neuropathic pain of rat. Methods: A model of neuropathic pain was made by injuring tibial nerve and sural nerve while common peroneal nerve was maintained. after 2 weeks, we performed behavioral tests for 7 days to try out mechnical allodynia using von frey filament and cold allodynia using acetone, which are calculated by counting withdrawal response on foot. Rat brains removed and sliced on 8th days. Serial sections were immunohistochemically reacted with polyclonal c-fos antibody. The numbers of c-Fos protein immunoreactive neurons in the central gray were examined using scion image program. Results: Mechanical allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. Cold allodynia in the SI3, BL40, SI3 BL40 groups were diminished compared with the control group. c-Fos protein expression on the central gray in the SI3 group were lower than that of the control group. Conclusions: We have noticed that acupuncture at SI3, BL40, SI3 BL40 diminished mechanical allodynia and cold allodynia in a model of neuropathic pain compared with the control group. c- Fos protein expression in the central gray of that group was also decreased compared with the control group. pain control using acupunture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

c-fos Expression in Bladder-Specific Spinal Neurons after Spinal Cord Injury Using Pseudorabies Virus

임영재,홍창희,진메화,이봉희,한상원 연세대학교의과대학 2008 Yonsei medical journal Vol.49 No.3

Purpose: c-fos expression in spinal neurons that are activated by lower urinary tract stimulation are not organ specific. In this experiment, we demonstrated changes of c-fos expression in bladder-specific preganglionic neurons (PGNs) and interneurons using pseudorabies virus (PRV). Materials and Methods: Forty Sprague-Dawley rats were used. We identified the neuronal pathway associated with the bladder by injecting PRV into the detrusor. An immunohistochemical method was used to stain Fos-protein encoded by the c-fos gene. Immunofluorescent staining for PRV was performed to evaluate changes in bladder- specific spinal neurons. Results: Immunofluorescent staining with choline acetyltransferase (ChAT) revealed that the sacral parasympathetic nucleus (SPN) regions contained 9.8 PGNs/ section. In rats with chronic spinal cord injury by intravesical saline instillation, 82.4±10.3% of PGNs in SPN exhibited Fos- immunoreactive (IR). Two and a half days after PRV infection, PRV-IR PGNs were observed at 5.4 PGNs/ section, and 2.7 ±1.6% of them exhibited Fos-IR. Unlike ChAT-IR PGNs, PRV-IR PGNs are bladder-specific neurons and PRV-IR and Fos-IR cells found in the back of PRV-IR PGNs are bladder- specific interneurons. Three days after PRV infection, we observed many PRV-IR and Fos-IR cells in the dorsal commissure. These neurons are interneurons distributed in the bladder. Conclusion: We confirmed that in chronic spinal cord injury, the patterns of c-fos expression in bladder-specific spinal neurons were similar to those in voiding-reflex related spinal neurons, which had already been demonstrated earlier. We believe that our methodology can be applied to study interactions between voiding and other organs as well, such as the urethra and prostate.