• 제목/요약/키워드: Ca homeostasis

검색결과 95건 처리시간 0.029초

Immunoreactivity of Calcium-Binding Proteins in the Central Auditory Nervous System of Aged Rats

  • Hong, Seok-Min;Chung, Seung-Young;Park, Moon-Sun;Huh, Young-Buhm;Park, Moon-Suh;Yeo, Seung-Gun
    • Journal of Korean Neurosurgical Society
    • /
    • 제45권4호
    • /
    • pp.231-235
    • /
    • 2009
  • Objective : While many factors contribute to aging, changes in calcium homeostasis and calcium related neuronal processes are likely to be important. High intracellular calcium is toxic to cells and alterations in calcium homeostasis are associated with changes in calcium-binding proteins, which confine free $Ca^{2+}$. We therefore assayed the expression of the calcium binding proteins calretinin and calbindin in the central auditory nervous system of rats. Methods : Using antibodies to calretinin and calbindin, we assayed their expression in the cochlear nucleus, superior olivary nucleus, inferior colliculus, medial geniculate body and auditory cortex of young (4 months old) and aged (24 months old) rats. Results : Calretinin and calbindin staining intensity in neurons of the cochlear nucleus was significantly higher in aged than in young rats (p<0.05) The number and staining intensity of calretinin-positive neurons in the inferior colliculus, and of calbindin-positive neurons in the superior olivary nucleus were greater in aged than in young rats (p<0.05). Conclusion : These results suggest that auditory processing is altered during aging, which may be due to increased intracellular $Ca^{2+}$ concentration, consequently leading to increased immunoreactivity toward calcium-binding proteins.

Forskolin의 흰쥐적출관류부신으로 부터 Ach, Excess $K^+$, DMPP, McN-A-343에 의한 Catecholamine 분비효과의 증강작용 (Forskolin-Induced Potentiation of Catecholamine Secretion Evoked By Ach, DMPP, McN-A-343 and Excess $K^+$ From the Rat Adrenal Gland)

  • 임동윤;김원식;최철희
    • 대한약리학회지
    • /
    • 제27권2호
    • /
    • pp.167-181
    • /
    • 1991
  • Adenylate cyclase 효소를 활성화시키는 약물인 Forskolin의 흰쥐 적출관류 부신으로부터 Ach, excess $K^+$, McN-A-343 및 caffein에 의한 catecholamines (CA) 분비작용에 대한 영향을 검색하고, 그 기전을 규명코자 연구를 시행하여 다음과 같은 연구결과를 얻었다. Forskolin (1.0 uM)은 흰쥐 부신적출정맥내로 1분동안 관류시킨 후 Ach(50 ug), excess $K^+$(56 mM), DMPP (100 uM) 및 caffeine (0.3 mM)에 의한 CA 분비작용을 현저히 증강시켰으나 McN-A-343에 의한 CA분비작용에는 영향을 미치지 않았다. Forskolin 자체는 CA분비작용을 일으키지 못하였다. 또한 세포의 calcium을 제거한 상태에서도 위 약물에 의한 CA분비작용에 대하여 유의한 증강작용을 나타내었다. 그러나 McN-A-343의 CA작용에는 영향이 없었으나 위의 약물의 CA분비작용을 유의하게 강화시켰다. Cyclic AMP를 증가시키는 약물로 알려져 있는 dibutyryl cyclic AMP (DBcAMP)는 300 uM농도를 1분간 관류시 Ach, excess $K^+$ 및 DMPP의 CA 분비작용을 뚜렷하게 증강시켰으나 McN-A-343 및 caffeine의 CA분비에는 별다른 영향이 없었다. DBcAMP 자체도 CA분비작용에는 영향을 미치지 못하였으나 또한 DBcAMP는 세포의 칼슘제거시에도 위의 약물에 의한 CA분비작용을 의의있게 증강시켰다. 그렇지만, McN-A-343의 CA분비작용은 증강시키지 못하였다. 이상의 연구결과로 보아 Forskolin는 adenylate cyclase를 활성화 시킴으로써 cyclic AMP 농도를 증가시켜 세포내로 칼슘유입을 증강시키며, 또한 세포내의 칼슘이동에도 관여함으로써 cholinergic nicotinic stimulation 및 depolarization에 의한 CA분비작용을 상승시키는 것으로 사료되어진다.

  • PDF

Propranolol이 심근 sarcoplasmic reticulum 및 mitochondria 의 $Ca^{++}$ 조절작용에 미치는 효과에 관한 연구 (Effect of Propranolol on the $Ca^{++}$-regulation of Cardiac Sarcoplasmic Reticulum and Mitochondria)

  • 최수승
    • Journal of Chest Surgery
    • /
    • 제19권2호
    • /
    • pp.197-208
    • /
    • 1986
  • Propranolol is one of clinically useful antiarrhythmic agents and electrophysiologically classified as group II. And the negative inotropic effect which is not related to adrenolytic effect has been demonstrated with high concentration of propranolol. On the other hand, it has been well known that the calcium plays a central role in excitation-contraction coupling process of myocardium and also in electrophysiological changes of cell membrane. Author studies the effect of propranolol on calcium uptake and release in sarcoplasmic reticulum and mitochondria prepared from porcine myocardium to investigate the mechanism of action of propranolol on myocardium. The results are summarized as follow: 1] The maximum Ca++-uptake of sarcoplasmic reticulum is inhibited by propranolol in a dose dependent manner. 2] The release of calcium from sarcoplasmic reticulum is not affected by propranolol but with higher than 1x10-3 M of propranolol, rate of calcium release from sarcoplasmic reticulum is decreased. 3] Propranolol inhibits the maximum uptake and uptake rate of calcium in mitochondria non-competitively. [Ki = 6.21 x 10-4 M] 4] The rate of Na+ induced calcium release from mitochondrion shows a function of [Na+]2 and is inhibited by propranolol with the concentration significantly lower than that affect the calcium uptake in sarcoplasmic reticulum and in mitochondria [Ki = 2.91 x 10-5 M]. These results suggest that propranolol affects the intracellular calcium homeostasis which may considered to be one of the mechanism of action of propranolol on myocardium.

  • PDF

Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C

  • Choi, Keun Hee;Shin, Choong Ho;Yang, Sei Won;Cheong, Hae Il
    • Clinical and Experimental Pediatrics
    • /
    • 제58권4호
    • /
    • pp.148-153
    • /
    • 2015
  • The calcium sensing receptor (CaSR) plays an important role in calcium homeostasis. Activating mutations of CaSR cause autosomal dominant hypocalcemia by affecting parathyroid hormone secretion in parathyroid gland and calcium resorption in kidney. They can also cause a type 5 Bartter syndrome by inhibiting the apical potassium channel in the thick ascending limb of the loop of Henle in the kidney. This study presents a patient who had autosomal dominant hypocalcemia with Bartter syndrome due to an activating mutation Y829C in the transmembrane domain of the CaSR. Symptoms of hypocalcemia occurred 12 days after birth and medication was started immediately. Medullary nephrocalcinosis and basal ganglia calcification were found at 7 years old and at 17 years old. Three hypercalcemic episodes occurred, one at 14 years old and two at 17 years old. The Bartter syndrome was not severe while the serum calcium concentration was controlled, but during hypercalcemic periods, the symptoms of Bartter syndrome were aggravated.

Alteration in NCX-3 immunoreactivity within the gerbil hippocampus following spontaneous seizures

  • Park, Dae-Kyoon;Park, Kyung-Ho;Ko, Jeong-Sik;Kim, Duk-Soo
    • BMB Reports
    • /
    • 제44권5호
    • /
    • pp.306-311
    • /
    • 2011
  • Although NCX-3 is highly expressed in the brain, the distribution of NCX-3 in the epileptic hippocampus is still controversial. Therefore, to assess the distribution and pattern of NCX-3 expression in epileptic hippocampus, we performed a comparative analysis of NCX-3 immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. In SR gerbils, NCX-3 immunoreactivity was higher than pre-seizure SS gerbils, particularly in the pavalbumin (PV)-positive interneurons. Three h post-ictal, NCX-3 immunoreactivity in the SS gerbil hippocampus was markedly elevated to the level of SR gerbils. Six h post-ictal, the expression of NCX-3 was reduced to the level of pre-seizure SS gerbils. Therefore, the results of the present study suggest that down-regulation of NCX-3 expression in the SS gerbil hippo-campus may be involved in the hyperexcitability of SS gerbils due to an imbalance of intracellular $Na^+/Ca^{2+}$ homeostasis and $Ca^{2+}$ concentration.

Channel Function of TRPML1 Prompts Lipolysis in Mature Adipocytes

  • Kim, Mi Seong;Kim, Min Seuk
    • International Journal of Oral Biology
    • /
    • 제43권1호
    • /
    • pp.23-27
    • /
    • 2018
  • Increased intracellular levels of $Ca^{2+}$ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated $Ca^{2+}$ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a $Ca^{2+}$-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

Glutamate에 의한 세포내 칼슘농도변화와 세포독성과의 관계 (Intracellular Calcium Concentration in the Glutamate-induced Cytotoxicity in PCl2 Cell)

  • 황인영;신임철;송연숙;성민제;박혜지;이윷모;박철범;이명구;오기완
    • Toxicological Research
    • /
    • 제18권4호
    • /
    • pp.355-362
    • /
    • 2002
  • Pathophysiological elevation of intracellular calcium concentration ($[Ca^{2+}]_1$) in the neuron has been considered as an important responsible factor in the neuronal cell damages. However the mechanism of increase of $[Ca^{2+}]_1$ and the relationship between $[Ca^{2+}]_1$ level and cytotocixity have not been fully demonstrated. In the present study, real-time alteration of $[Ca^{2+}]_1$and cellular response (cell damages) in the pheochromocytoma cells (PC12) stimulated by glutamate were investigated. Glutamate dose dependently decreased cell viability determined propidium iodide fluorescence method and morphology change. Conversely related with cell damages, glutamate dose dependently increased the level of[Ca$^{2+}$$_{i}$ . To investigate the mechanism of glutamate-induced increase of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$, was first measured in the cell cultured in calcium free media and in the presence of dantrolene, an inhibitor of calcium release from ryanodine receptor located in endoplasmic reticulum (ER). Similar to the increase$[Ca^{2+}]_1$ in the calcium-containing media, glutamate dose dependently increased $[Ca^{2+}]_1$ in the cell cultured in free calcium media. However pretreatment (2 hr) with 20~50 $\mu\textrm{M}$ dantrolene substantial lowered glutamate-induced increase of $[Ca^{2+}]_1$, suggesting that release of calcium from ER may be major sourse of increase of $[Ca^{2+}]_1$ in PC12 cells. Dantrolene-induced inhibition of $[Ca^{2+}]_1$ resulted in recovery of cytotoxicity by glutamate. Relevance of N-methy-D-aspartate (NMDA) receptor, a type of glutamte receptor on glutamate-induced incense of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$ was also determined in the cells pretreated (2 hr) with NMDA receptor antagonist MK-80l. Glutamate-induced increase of $[Ca^{2+}]_1$ was reduced by MK-801 dose dependently. Furthermore, glutamate-induced cytotoxicity was also prevented by MK-80l. These results demonstrate that glutamte increase $[Ca^{2+}]_1$ dose dependently and thereby cause cytotoxicity. The increase of $[Ca^{2+}]_1$ may release from ER, especially through ryanodine receptor and/or through NMDA receptor Alteration of calcium homeostasis through disturbance of ER system and/or calcium influx through NMDA receptor could contribute glutamate-induced cell damages.s.

Calmodulin of Olive Flounder Paralichthys olivaceus : Cloning and Expression Analysis

  • Hong, Gyeong-Eun;Kong, Hee Jeong;Nam, Bo-Hye;Kim, Young-Ok;Kim, Woo-Jin;Lee, Sang-Jun;Choi, Tae-Jin
    • 한국해양바이오학회지
    • /
    • 제2권4호
    • /
    • pp.234-237
    • /
    • 2007
  • Calmodulin은 $Ca^{2+}$ 결합단백질로서 생체 내에서 $Ca^{2+}$ 의존적 기작을 통하여 다양한 생물학적 기능에 관여한다. 본 연구에서는 넙치 Paralichthys olivaceus의 cDNA library로부터 Calmodulin cDNA를 분리 동정하였다. 염기 서열 및 아미노산 서열을 분석한 결과, 넙치 Calmodulin cDNA는 782개의 nucleotides로 구성되어 있고, 4개의 잘 보존된 $Ca^{2+}$결합 motifs (EF-I, EF-II, EF-III, EF-IV)를 가지는 149개의 아미노산 잔기를 전사할 수 있는 open reading frame을 포함한다. 또한 번역된 아미노산 서열은 인간, 쥐, zebrafish, 개구리의 Calmodulin 아미노산 서열과 100% 동일성을 보이며 보라성게, 침팬지의 Calmodulin 아미노산 서열과 각각 97, 99%의 동일성을 보인다. 넙치 Calmodulin 전사체는 뇌와 장 조직에서 많은 양이 발현되었고, 신장, 아가미, 눈, 근육, 피부, 지느러미에서도 발현이 관찰되었다. 또한 넙치 Calmodulin 전사체는 수정 후 7일째의 발생 초기 단계 시료에서도 발현되어 수정 후 34일째까지 그 발현이 서서히 증가하였다. 이상의 결과들로부터 넙치 Calmodulin은 넙치의 발생 초기 단계에서 필요한 단백질로 생각되며 아마 항상성 유지에 중요한 역할을 할 것으로 예상된다.

  • PDF

Solute Carrier SLC41A1 'A MINI REVIEW'

  • Basnet Hom Bahadur
    • 한국환경성돌연변이발암원학회지
    • /
    • 제25권2호
    • /
    • pp.60-65
    • /
    • 2005
  • The human solute carrier, SLC41Al, is a $Mg^{2}+$ transporter that is regulated by extracellular magnesium. Although intracellular magnesium plays a fundamental role in cellular metabolism, little is known about how $Mg^{2}+$ is taken up and controlled by cells. Magnesium plays a fundamental role in cellular metabolism so that its control within the body is critical. Magnesium homeostasis is principally a balance between intestinal absorption of dietary magnesium and renal excretion of urinary magnesium. The kidney, mainly the distal convoluted tubule, controls magnesium reabsorption. Although renal reabsorption is under the influence of many hormones, selective regulation of magnesium transport is due to intrinsic control involving transcriptional processes and synthesis of transport proteins. Using microarray analysis, identification of the genetic elements involved with this transcriptional control has been begun. SLC41A1(GenBank Accession No. AJ514402), comprises 10 putative transmembrane domains, two of which are highly homologous to the integral membrane part of the prokaryote transports $Mg^{2}+$ and other divalent cations $Sr^2+,\;Zn^2+,\;Cu^2+,\;Fe^2+,\;Co^2+,\;Ba^2+,\;and\;Cd^2+,\;but\;not\;Ca^2+,\;Mn^2+,\;and\;Ni^2+.$ Transport of $Mg^{2}+$ by SLC41Al is rheogenic, voltage dependent, and not coupled to Na or Cl. Expressed SLC41Al transports a range of other divalent cations: $Mg^{2+},\;Sr^{2+},\;Zn^{2+},\;Cu^{2+},\;Fe^{2+},\;Co^{2+},\;Ba^{2+},\;and\;Cd^{2+}$. The divalent cations $Ca^{2+},\;Mn^{2+},\;and\;Ni^{2+}$and the trivalent ion $Gd^{3+}$ did not induce currents nor did they inhibit $Mg^{2+}$ transport. The nonselective cation $La^{3+}$ abolishes $Mg^{2+}$ uptake. Computer analysis of the SLC41Al protein structure reveals that it belongs to MgtE protein family & suggested that the human solute carrier, SLC41Al, might be a eukaryotic $Mg^{2+}$ transporter closely related $(60-70\%)$ protein encoded by SLC41A2 is a $Mg^{2}+$ transporter that might be involved in magnesium homeostasis in epithelial cells also transports a range of other divalent cations: $Ba^2,\;Ni^2,\;CO^2,\;Fe^2,\;or\;Mn^2,\;but\;not\;Ca^2,\;Zn^2,\;or\;Cu^{2+}$ that may have related functional properties.

  • PDF

종대황과 선복화 에탄올 추출물의 인간 피부 세포주인 HaCaT 세포에서 NRF2/ARE에 의존적인 유전자 발현의 유도를 통한 항산화 효과 (Ethanol Extracts of Rheum undulatum and Inula japonica Protect Against Oxidative Damages on Human Keratinocyte HaCaT cells through the Induction of ARE/NRF2-dependent Phase II Cytoprotective Enzymes)

  • 유옥경;이용걸;도기환;금영삼
    • 생명과학회지
    • /
    • 제27권3호
    • /
    • pp.310-317
    • /
    • 2017
  • 본 연구진은 HaCaT-ARE-luciferase 세포를 이용하여 400 여개의 약용식물 에탄올 추출물 중 NRF2/ARE 유도효과가 있는 신규 추출물을 검색하였고 이를 통하여 종대황(Rheum undulatum)과 선복화(Inula japonica)의 주정 추출물이 HaCaT-ARE-luciferase 세포에서 ARE 활성을 강하게 유도하는 것을 관찰하였다. 종대황과 선복화 에탄올 추출물은 HaCaT 세포에서 생존(viability)을 증가시켰고 NRF2/ARE에 의존적인 phase II cytoprotective 효소인 heme oxygenase-1 (HO-1)와 NADPH:quinone oxidoreductase-1 (NQO1)의 전사 및 단백질 발현을 강하게 유도하였다. 또한 종대황과 선복화 추출물은 HaCaT 세포에서 TPA로 유도한 세포 내 활성 산소 및 이를 통하여 생성되는 스트레스 마커인 8-hydroxydeoxyguanosine (8-OH-dG)과 4-hydroxynonenal (4HNE)의 발생을 강하게 억제하였다. 본 연구는 종대황과 선복화의 에탄올 추출물이 인간 피부 세포주인 HaCaT 세포에서 NRF2/ARE에 의존적인 유전자 발현의 유도를 통하여 강력한 항산화 효과를 발휘한다는 것을 증명한다.