• BMB Reports
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• 제47권2호
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• pp.69-79
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• 2014

$Ca^{2+}$ release from intracellular stores and influx from extracellular reservoir regulate a wide range of physiological functions including muscle contraction and rhythmic heartbeat. One of the most ubiquitous pathways involved in controlled $Ca^{2+}$ influx into cells is store-operated $Ca^{2+}$ entry (SOCE), which is activated by the reduction of $Ca^{2+}$ concentration in the lumen of endoplasmic or sarcoplasmic reticulum (ER/SR). Although SOCE is pronounced in non-excitable cells, accumulating evidences highlight its presence and important roles in skeletal muscle and heart. Recent discovery of STIM proteins as ER/SR $Ca^{2+}$ sensors and Orai proteins as $Ca^{2+}$ channel pore forming unit expedited the mechanistic understanding of this pathway. This review focuses on current advances of SOCE components, regulation and physiologic and pathophysiologic roles in muscles. The specific property and the dysfunction of this pathway in muscle diseases, and new directions for future research in this rapidly growing field are discussed.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.93-103
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• 2024

Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca²⁺ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca²⁺ entry (SOCE) which is critical for cellular Ca²⁺ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca²⁺ stores were depleted in the absence of extracellular Ca²⁺, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca²⁺ entry channels. Intracellular Ca²⁺ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca²⁺ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.

• Tuberculosis and Respiratory Diseases
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• 제85권2호
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• pp.147-154
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• 2022

Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drug-resistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear. Methods: Afatinib-mediated changes in the level of store-operated Ca²⁺ entry (SOCE)-related proteins and intracellular Ca²⁺ level in non-small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation. Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca²⁺ ATPase [SERCA2]) decreased after afatinib treatment in non-small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinib-resistant non-small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca²⁺. Moreover, extracellular Ca²⁺ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca²⁺. Conclusion: Extracellular Ca²⁺ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca²⁺ is essential for determining anti-cancer drug efficacy.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.1-8
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• 2013

Understanding the cellular and molecular mechanisms involved in the development and progression of pulmonary hypertension (PH) remains imperative if we are to successfully improve the quality of life and life span of patients with the disease. A whole plethora of mechanisms are associated with the development and progression of PH. Such complexity makes it difficult to isolate one particular pathway to target clinically. Changes in intracellular free calcium concentration, the most common intracellular second messenger, can have significant impact in defining the pathogenic mechanisms leading to its development and persistence. Signaling pathways leading to the elevation of $[Ca^{2+}]_{cyt}$ contribute to pulmonary vasoconstriction, excessive proliferation of smooth muscle cells and ultimately pulmonary vascular remodeling. This current review serves to summarize the some of the most recent advances in the regulation of calcium during pulmonary hypertension.

• KSBB Journal
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• 제23권1호
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• pp.37-43
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• 2008

(주)녹십자는 1986년 "훽나인"을 B형 혈우병 치료제로 제조품목허가를 받아 B형 혈우병치료제 공급을 시작하였다. 또한 1991년 New York Blood Center에서 selvent/detergent 바이러스 불활화 방법을 도입하여 제조공정에 추가한 후 혈액유래 바이러스로부터 안전한 제품을 생산하여 왔다. 하지만 이 제품은 혈액응고 제2인자, 제7인자, 제10인자가 함유된 제9인자 복합체로, 정맥 혈전증과 파종성 혈관내응고병증 같은 혈전형성 부작용이 일어날 가능성이 있어, 훽나인보다 순도, 유효성, 바이러스 안전성이 우수한 제품의 개발이 필요하였다. 이를 위해 고순도 제9인자 제제인 "GreenNine VF" 제조공정을 개발하였다. GreenNine VF 제조공정은 기존의 훽나인 생산 공정에 heparin 친화성 크로마토그래피와 양이온 크로마토그래피가 추가된 공정으로, 바이러스 안전성을 증진시키기 위한 바이러스 필터 공정도 포함하고 있다. 이러한 공정에 의해서 산업적 규모로 생산된 GreenNine VF는 훽나인에 비해 순도와 바이러스 안전성이 월등히 높은 것으로 확인되었다. 또한 고순도 혈액응고 제9인자 제제인 Mononine, Octanyne, Berinin HS, Immunine STIM plus 600보다 순도가 더 높았다. Cryo-poor plasma 1,600 L를 원료로 사용했을 때 1 batch 당 250IU 분병제품 2,400병 이상, 500 IU 분병제품 1,200병 이상을 생산할 수 있었다.

• 생물정신의학
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• 제2권1호
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• pp.28-37
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• 1995

Clinical neuropsychology which belongs to the necuroscience field is concerned with relationship between human behaviors and the brain structure. Clinical neuropsychology has grown to be a specialized separate field within psychology over the last twenty years. Clinical neuropsychology offers an objective methodology to consider the mind-body interaction and evaluate the behavioral consequences and functional deficits associated with brain lesions. Clinical neuropsychological assessment is composed of cognitive, perceptual, motor and emotional function through various neuropsychological examinations such as Halsted-Reitan and Luria-Nebraska batteries, and computerized neuropsychological test such as PCIS Vienna Test System and Stim. The goals of neuropsychological evaluation are to identify of neuropsychological dysfuncitions, to develop execute and monitor treatment plans, and to make rehabilitation programs. Recently, the neuropsychiatric patients are increasing in number and 15-20% of acute psychiatric patients suffer from organic mental problems. Moreover, clinical neuropsychology has an increasingly important role in both neurobehavioral foundation and clinical application. So, psychiatrists must play a major role in the development of clinical neuropsychology in psychiatry.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.363-372
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• 2020

Gardenia jasminoides (GJ) is a widely used herbal medicine with anti-inflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJ_EtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJ_EtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJ_HEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJ_HEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited I_ORAI1 and interleukin-2 production in CD3/CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4⁺ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

• Journal of Korean Neurosurgical Society
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• 제61권1호
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• pp.66-74
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• 2018

Objective : The aim of this study was to identify the susceptibility genes responsible for lumbar spondylosis (LS) in Korean patients. Methods : Data from 1427 subjects were made available for radiographic grading and genome wide association studies (GWAS) analysis. Lateral lumbar spine radiographs were obtained and the various degrees of degenerative change were semi-quantitatively scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single-nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed and the association between the SNPs and case-control status was analyzed by stepwise logistic regression analyses. Results : The top 100 SNPs with a cutoff p-value of less than $3.7{\times}10^{-4}$ were selected for joint space narrowing, while a cutoff p-value of $6.0{\times}10^{-4}$ was applied to osteophytes and the Kellgren-Lawrence (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds ratio [OR]=17.58, $p=1.6{\times}10^{-4}$), stromal interaction molecule 2 (STIM1, rs210781, OR=5.53, $p=5{\times}10^{-4}$), and transient receptor potential cation channel, subfamily C (rs11224760, OR=3.99, $p=4.8{\times}10^{-4}$), respectively. Leucine-rich repeat-containing G protein-coupled receptor 4 was significantly associated with both disc space narrowing and osteophytes (rs1979400, OR=2.01, $p=1.1{\times}10^{-4}$ for disc space narrowing, OR=1.79, $p=3{\times}10^{-4}$ for osteophytes), while zinc finger and BTB domain containing 7C was significantly and negatively associated with both osteophytes and a K-L grade >2 (rs12457004,OR=0.25, $p=5.8{\times}10^{-4}$ and OR=0.27, $p=5.3{\times}10^{-4}$, respectively). Conclusion : We identified SNPs that potentially contribute to the pathogenesis of LS. This is the first report of a GWAS in an Asian population.

• 수면정신생리
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• 제9권1호
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• pp.41-47
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• 2002

목 적 : 여러 모의 연구(simulated study)에서 순환제 교대근무자의 야간 근무에 따른 수면장애와 작업수행의 어려움에 대해 광치료가 치료적 도구로 제안되고 있어 실제 순환제 교대 근무 환경에서의 야간 근무 동안 광치료의 효과를 평가하고자 하였다. 방 법 : 연구대상인 5명의 병동 근무 간호사들은 기초평가단계 동안 연속적인 3일간의 낮 근무 후 650 lux의 실내 조명 하에서 연속적인 3일간의 야간근무를 하도록 계획되었으며, 2주 후의 광치료시행단계에서는 동일한 순환주기로 근무하는 동안 자정부터 오전 4시까지 2500 lux의 광박스를 이용한 광치료를 시행하였다. 야간근무 후의 낮수면은 actiwatch를 이용하여 평가되었으며 야간 근무 동안은 스탠포드 졸리움 척도를 이용한 각성상태, 고막체온, STIM을 이용한 수행능력 및 visual analogue를 이용한 우울감, 불안감, 신체적 불편감, 피로감을 기초평가단계와 광치료시행단계 각각에서 야간근무 첫째날과 셋째날을 비교평가하였다. 결 과 : 야간근무 후의 낮 수면은 기초평가단계와 광치료 시행단계 모두 야간 근무 1일째와 3일째에 유의한 차이를 보이지 않았다. 일주기리듬의 위상 변화를 알아보기 위해 측정된 고막 온도는 야간근무 3일째에 기초평가단계에서는 위상전진을 나타낸 반면 광치료시행단계에서는 위상변화가 없었다. 또한, 각성상태, 우울감, 불안감, 피로감, 신체적 불편감, 졸리움 등의 변화도 기초평가단계에서 야간근무 3일째에 유의하게 악화된 반면 광치료시행단계에서는 변화가 없었다. 주의력에서는 광치료시행단계에서만 야간근무 3일째가 1일째에 비해 유의하게 호전되는 양상을 나타내었다. 결 론 : 본 연구는 위약효과를 배제할 수는 없지만, 실제근무 환경에서 단기간의 광치료가 순환제 교대근무자들의 주간 수면의 질을 뚜렷하게 변화시키진 않았으나, 야간 근무동안 졸리움 감소와 주의력 향상을 통한 야간 업무 수행능력의 호전 가능성을 제시해 주고 있다.

• 대한지역사회작업치료학회지
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• 제5권1호
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• pp.23-34
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• 2015

목적 : 신경근 전기자극치료와 함께 적용된 자가 삼킴 운동이 삼킴 장애 환자의 삼킴 기능 향상에 미치는 효과를 알아보고자 하였다. 연구방법 : 2013년 5월부터 2015년 4월까지 서울 소재 A 종합병원에서 삼킴 장애로 진단받아 삼킴 재활치료가 의뢰된 입원 환자들을 대조군과 실험군으로 나누었다. 두 군 모두 VitalStim을 이용해 신경근 전기자극치료를 받는 60분 동안 30분간 삼킴 재활치료를 받았고, 실험군은 추가적으로 남는 30분간 자가 삼킴 운동 프로그램을 시행하였다. 중재는 3주간 주 5회 진행되었다. 의무기록 열람을 통해 대상자들의 일반적 정보를 조사하였고, 중재 전후 삼킴 기능의 변화를 알아보기 위해 비디오 투시 삼킴 장애 검사와 침습-흡인 척도를 시행하였다. 결과 : 중재 전 두 군의 삼킴 기능에 유의한 차이가 없었다. 중재 전후 대조군은 비디오 투시 삼킴 장애 척도 총점, 조롱박오목의 잔여물과 흡인에서 유의한 차이를 보였고, 실험군은 비디오 투시 삼킴 장애 척도 총점, 후두개계곡의 잔여물, 조롱박오목의 잔여물에서 유의한 차이를 보였다(p<.05). 중재 전후 대조군과 실험군의 삼킴 기능 차이를 비교한 결과 유의한 차이가 없었다. 결론 : 신경근 전기자극치료와 함께 적용된 삼킴 재활치료 또는 삼킴 재활치료와 자가 삼킴 운동이 삼킴 장애 환자의 인후두 기능 향상에 유의한 영향을 미침을 알 수 있었으나 추가적으로 적용된 자가 삼킴 운동이 유의한 변수로 작용하지 않음을 알 수 있었다.