• 제목/요약/키워드: protein kinase C

검색결과 453건 처리시간 0.12초

Antagonists of NMDA Receptor, Calcium Channel and Protein Kinase C Potentiate Inhibitory Action of Morphine on Responses of Rat Dorsal Horn Neuron

  • Shin, Hong-Kee;Kim, Yeon-Suk;Jun, Jong-Hun;Lee, Seo-Eun;Kim, Jae-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • 제7권5호
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    • pp.251-254
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    • 2003
  • The present study was designed to examine whether the co-application of morphine with $Ca^{2+}$ channel antagonist $(Mn^{2+},\;verapamil)$, N-methyl-D-aspartate (NMDA) receptor antagonist (2-amino-5-phosphonopentanoic acid$[AP_5]$, $Mg^{2+}$) or protein kinase C inhibitor (H-7) causes the potentiation of morphine-induced antinociceptive action by using an in vivo electrophysiological technique. A single iontophoretic application of morphine or an antagonist alone induced weak inhibition of wide dynamic range (WDR) cell responses to iontophoretically applied NMDA and C-fiber stimulation. Although there was a little difference in the potentiating effects, the antinociceptive action of morphine was potentiated when morphine was iontophoretically applied together with $Mn^{2+}$, verapamil, $AP_5$, $Mg^{2+}$ or H-7. However, the potentiating action between morphine and each antagonist was not apparent, when the antinociceptive action evoked by morphine or the antagonist alone was too strong. These results suggest that the potentiating effect can be caused by the interaction between morphine and each antagonist in the spinal dorsal horn.

Protein Kinase C-delta Stimulates Haptoglobin Secretion

  • Oh, Mi-Kyung;Park, Seon-Joo;Kim, Nam-Hoon;Kim, In-Sook
    • BMB Reports
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    • 제40권1호
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    • pp.130-134
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    • 2007
  • Haptoglobin (Hp) is a glycoprotein that is produced by hepatic cells and secreted into the circulation. While studying the physiologic functions of Hp, we found that Hp synthesized in THP-1 monocytic cells was largely retained within cells, although Hp is considered a secretory protein. To investigate the molecular mechanism on Hp secretion in THP-1 cells, in the present study, we examined the effect of protein kinase C (PKC) on Hp secretion. When several inhibitors of PKC isoforms were tested, only Rottlerin, a specific inhibitor of PKC-$\delta$, completely blocked Hp secretion from cells to culture medium. To confirm the role of PKC-$\delta$ in Hp secretion, Hp-overexpressing COS7 cells were transiently transfected with a wild-type or a dominantnegative mutant of the PKC-$\delta$ gene. Mutant PKC-$\delta$ significantly inhibited Hp secretion, whereas the wild-type gene slightly increased Hp secretion. These results demonstrate that the PKC-$\delta$ signal is involved in Hp secretion.

Lysophosphatidylcholine Enhances Chondrogenesis by the Modulation of Protein Kinase C Isoform Expression

  • Lee, Sun-Ryung;Lee, Young-Sup;Chun, Jang-Soo;Sonn, Jong-Kyoung;Kang, Shin-Sung
    • Animal cells and systems
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    • 제2권2호
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    • pp.229-232
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    • 1998
  • Lysophosphatidylcholine (LPC) has been reported to be responsible for the sustained activation of protein kinase C (PKC). As chondroqenesis is known to be regulated by PKC, this study was performed to investigate the effects of LPC on chondrogenesis of chick limb bud mesenchymes in vitro. LPC treatment of mesenchymes during micromass culture significantly enhanced chondrogenic differentiation. The most effective time of LPC on the stimulation of chondrogenesis was the first day of micromass culture. Analysis of LPC effects on the expression of PKC isoforms revealed that LPC treatment increased expression of PKCa, among the multiple PKC isoforms, in the membrane fraction on day one of culture. The stimulatory effect of LPC on chondrogenesis was abolished if PKCa was down regulated by the prolonged treatment of cells with phorbol ester. The results suqqest that LPC promotes chondrogenesis through the activation of PKCa at the early stage of chondrogenic differentiation.

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Identification of Phosphatidylcholine-Phospholipase D and Activation Mechanisms in Rabbit Kidney Proximal Tubule Cells

  • Chung, Jin-Ho;Chae, Joo-Byung;Chung, Sung-Hyun
    • BMB Reports
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    • 제29권1호
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    • pp.11-16
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    • 1996
  • The present study showed that receptor-mediated activation of rabbit kidney proximal tubule cells by angiotensin II, the $Ca^{2+}$ ionophore A23187, or the protein kinase C activator phorbol myristate acetate (PMA) all stimulated phospholipase D (PLD). This was demonstrated by the increased formation of phosphatidic acid, and in the presence of 0.5% ethanol, phosphatidylethanol (PEt) accumulation. Angiotensin II leads to a rapid increase in phosphatidic acid and diacylglycerol, and phosphatidic acid formation preceeded the formation of diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine hydrolyzed by Pill. On the other hand, EGTA substantially attenuated angiotensin II and A23187-induced PEt formation, and when the cells were pretreated with verapamil angiotensin II-induced Pill activation was completely abolished. These results provide the evidence that calcium ion influx is essential for the agonist-induced Pill activation. In addition, staurosporine, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but was ineffective on angiotensin II-induced PEt accumulation. $GTP{\gamma}S$ also stimulates PEt formation in digitonin-permeabilized cells, but pretreatment of the cells with pertussis toxin failed to suppress angiotensin II-induced PEt formation. From these results, we conclude that in the rabbit kidney proximal tubule cells the mechanisms of angiotensin II- and PMA-induced Pill activation are different from each other and mediated via a pertussis toxin-insensitive trimeric G protein.

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Brazilin Inhibits Activities of Protein Kinase C and Insulin Receptor Serine Kinase in Rat Liver

  • Kim, Seong-Gon;Kim, You-Me;Khil, Lee-Yong;Jeon, Sun-Duck;So, Dhong-Su;Moon, Chang-Hyun;Moon, Chang-Kiu
    • Archives of Pharmacal Research
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    • 제21권2호
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    • pp.140-146
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    • 1998
  • Hypoglycemic action of brazilin was found to be based on the improvement of peripheral glucose utility, and this action might be correlated with the insulin action pathway. In the present study we investigated the effect of brazilin on the insulin receptor autophosphorylation, protein kinase C (PKC), protein phosphatase and insulin receptor serine kinase in order to confirm whether the hypoglycemic mechanism is concerned with insulin action pathway. Brazilin was found to inhibit PKC and insulin receptor serine kinase, which are involved in the regulation of insulin signal pathway. But any significant effect was not shown on insulin receptor tyrosine kinase activity, autophosphorylation and phosphatase activity. These findings suggest that brazilin might enhance insulin receptor function by decreasing serine phosphorylation, which might mediate hypoglycemic effect of brazilin.

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Bradykinin-Mediated Stimulation of Phospholipase D in Rabbit Kidney Proximal Tubule Cells

  • Park, Kyung-Hyup;Jung, Jee-Chang;Chung, Sung-Hyun
    • Biomolecules & Therapeutics
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    • 제2권1호
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    • pp.39-46
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    • 1994
  • The present study was undertaken to demonstrate whether or not bradykinin activates a phospholipase D in rabbit kidney proximal tubule cells. By measuring the formation of [$^3$H]phosphatidic acid and [$^3$H]phosphatidylethanol we could elucidate the direct stimulation of phospholipase D by bradykinin. Bradykinin leads to a rapid increase in [$^3$H]phosphatidic acid and [$^3$H]diacylglycerol, and [$^3$H]phosphatidic acid formation preceded the formation of [$^3$H]diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine by the action of phospholipase D, not from diacylglycerol by the action of diacylglycerol kinase. In addition, the other mechanisms by which phospholipase D is activated was examined. We have found that phospholipase D was activated and regulated by extracellular calcium ion and pertussis toxin-insensitive G protein, respectively. It has also been shown that bradykinin may activate phospholipase D through protein kinase C-dependent pathway. In conclusion, we are now, for the first time, strongly suggesting that bradykinin-induced activation of phospholipase D in the rabbit kidney proximal tubule cells is mediated by a pertussis toxin-insensitive G protein and is dependent of protein kinase C.

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Phosphorylation of a 66 kDa Protein, a Putative Protein Kinase C Substrate, is Related to Chondrogenesis of Chick Embryo Mesenchymes In Vitro

  • Lee, Sun-Ryung;Sonn, Jong-Kyung;Yoo, Byung-Je;Lim, Young-Bin;Kang, Shin-Sung
    • BMB Reports
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    • 제31권4호
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    • pp.350-354
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    • 1998
  • To understand the role of protein kinase C (PKC) in the regulation of chondrogenesis, we examined proteins which are phosphorylated by PKC. Stage 23/24 chick embryo wing mesenchymes were micromass-cultured to induce chondrogenesis and cell extracts were phosphorylated in a condition that activates PKC. Several proteins including 63 and 66 kDa proteins were phosphorylated. The 66 kDa protein was phosphorylated only in the presence of phorbol 12-myristate 13-acetate (PMA) and phosphatidylserine CPS), and the phosphorylation was almost completely diminished by bisindolylmaleimide, a PKC inhibitor. In addition, partially purified PKC increased the phosphorylation of the 66 kDa protein. Treatment of cultures with lysophosphatidylcholine (LPC) promoted chondrogenesis and phosphorylation of 66 kDa protein, while PMA and thymeleatoxin inhibited both of the two events. Our results suggest that the 66 kDa protein is a putative substrate of PKC, and phosphorylation of the 66 kDa protein, probably by $PKC\alpha$ is required for chondrogenesis.

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Endosulfan Induces CYP1A1 Expression Mediated through Aryl Hydrocarbon Receptor Signal Transduction by Protein Kinase C

  • Han, Eun Hee;Kim, Hyung Gyun;Lee, Eun Ji;Jeong, Hye Gwang
    • Toxicological Research
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    • 제31권4호
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    • pp.339-345
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    • 2015
  • CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.

흡연특이성 발암물질이 특정 Protein Kinase C Isoform에 미치는 영향 (Effects of Tobacco-Specific Carcinogen on Protein Kinase C Isoforms)

  • 강형석;고무성;박기성;이섭;전상훈;권오춘
    • Journal of Chest Surgery
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    • 제36권9호
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    • pp.666-673
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    • 2003
  • 폐암의 주된 원인으로 알려진 흡연은 그 악성세포 발현기전이 아직 정확히 규명된 바 없다. 이에 저자들은 흡연에 의한 발암성의 지표로 흡연 중에 특이적으로 존재하는 강력한 발암물질인 NNK(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone)를 이용하여 흡연에 따른 폐암의 발생과 그 Protein kinase C (PKC) isoform과 관련된 기전에 관한 연구를 시도하였다. 대상 및 방법: 인체 상피세포를 NNK에 노출시킨 후 saturation density, soft agar colony formation, cell aggregation 및 foci의 출현 등의 양상을 파악하여 세포 발암성 여부를 관찰하였으며 NNK를 15분간 노출시킨 후 PKC의 변화는 세포 내 PKC isoform의 양을 cytosolic fraction과 membrane fraction으로 분리하여 측정하여 분석하였다. 결과: NNK 투여군에서 saturation density, soft agar colony formation, cell aggregation 및 foci의 출현 시기 등의 세포 발암성을 뚜렷이 나타내었으며 PKC isoform분석의 경우 PKC-$\alpha$의 membrane fraction의 뚜렷한 증가를 보였으며 이러한 활성은 용량-의존적인 형태를 유지하였다. PKC-$\varepsilon$은 NNK 처리 시 용량-의존적으로 cytosol fraction의 감소 및 membrane fraction의 증가를 뚜렷하게 보였고 NNK에 의한 PKC-λ의 변화는 감지되지 않았다. 결론: 본 연구는 화학적 발암물질인 NNK가 인체발암화에 관여함을 재차 확인하면서 초기 과정에 관여하는 PKC isoform의 변화를 분석함으로써 total PKC활성이 아닌 isoform 각각에 대한 변화를 확인하였다는 점에서 앞으로 인체상피세포 기원의 폐암 생성 기전 연구에 기여할 것으로 생각한다.

피부화상으로 유도된 심근손상에서 Protein Kinase C의 역할 (The Role of Protein Kinase C in the Cardiac Injury Induced by Skin Burn)

  • 문혜정;조현국;박원학
    • Applied Microscopy
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    • 제33권4호
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    • pp.299-313
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    • 2003
  • 본 연구는 피부화상으로 유도된 심근손상에서 protein kinase C (PKC)의 역할을 알아보고자 하였다. 수컷 흰 쥐(SD계)에 15%의 피부전층화상을 유도한 뒤, PKC activator인 phorbol 12-myristate 13-acetate (PMA)와 PKC inhibitor인 bisindolylmaleimide (BIS)를 투여하여 5시간, 24시간 후에 심장을 적출하여 생화학적 미세구조적 입체해석학적 방법을 실시하였다. 혈청 AST와 creatinine 은 화상 후 5시간군과 화상 후 5시간+BIS 투여군에서 높게 나타났고, KC와 MPO 활성은 PMA 투여군이 BIS 투여군보다 낮게 나타났다. 미세구조적 관찰 결과 PMA 투여군에서는, 화상으로 인한 핵의 분열, 과수축대 형성, 사이원반의 분리 현상이 다소 완화된 형태로 관찰되었고, BIS 투여군에서는 화상 단독군에서 나타나는 형태적 변화 뿐만 아니라 비정상적인 형태의 사립체도 일부 관찰되었다. 전체적으로 5시간에서 24시간군으로 가면서 손상이 완화된 양상을 나타내었다. 입체해석학적 결과에서는 화상으로 인한 근원섬유의 체적밀도 감소가 PMA와 BIS 투여로 인해 증가되었고, 사립체의 체적밀도와 수밀도의 증가는 BIS군에서 가장 높게 나타났다. 결론적으로 PKC의 활성화는 화상으로 인해 손상된 심근에서 염증반응을 감소시켜 심근 손상을 보호한다고 사료된다.