首乌丹参方预处理对大鼠心肌缺血再灌注损伤PKC与iNOS mRNA表达的影响

目的观察首乌丹参方(GTSMP)对大鼠心肌缺血再灌注损伤(I/R)保护作用。方法将实验大鼠分为假手术组、模型组、首乌丹参方高剂量组(9g生药/kg)、首乌丹参方中剂量组(4.5g生药/kg)、首乌丹参方低剂量组(2.25g生药/kg)、阳性对照药复方丹参滴丸组(4.5g生药/kg)、工具对照药消心痛组(1.67mg/kg),共7组。采用结扎大鼠冠状动脉前降支30min/开放120min建立心肌I/R模型。通过RT-PCR分子生物学方法,观察蛋白激酶C(PKC) mRNA和iNOS mRNA的表达情况以及首乌丹参方预处理对其的影响。结果与假手术组相比,模型组和首乌丹参方各组PKC mRNA表达均有所下降;与模型组相比,首乌丹参方中剂量组、复方丹参滴丸组和消心痛组表达上调,均表现出显著性差异,首乌丹参方高剂量组及低剂量组也能促进PKC mRNA的表达,但没有显著性差异;假手术组心肌iNOS mRNA弱表达,模型组呈现高表达,首乌丹参方可下调iNOS mRNA基因表达。结论首乌丹参方预处理可促进I/R的大鼠心肌的PKC表达,下调I/R大鼠心肌iNOS mRNA的表达;其通过激动PKC,使心肌组织iNOS mRNA弱表达,可能是首乌丹参方对缺血再灌注损伤的心肌的保护效应机制之一。     

核因子-kappa B活化对鼻息肉组织中PKC、IL-8表达活性的影响

目的探讨核因子-kappa B p65(NF-κB p65)活化对鼻息肉组织中蛋白激酶C-α(PKC-α)和白细胞介素- 8(IL-8)表达的影响及其在鼻息肉发病机制中的可能作用。方法息肉组织标本35例,正常下鼻甲黏膜16例,免疫组织化学技术检测NF-κB p65、PKC-α、IL-8的表达活性。结果鼻息肉中的NF-κB p65、PKC-α和IL-8表达活性明显高于下鼻甲黏膜,差异有统计学意义(P<0.01);NF-κB p65表达活性与PKC-α和IL-8呈正相关(r分别为0.902,0.946,P<0.01);PKC-α表达活性与IL-8呈正相关(r=0.970,P<0.01)。结论NF-κB-PKC信号传导通道可以调节IL-8的表达活性,是鼻息肉发病的重要机制之一。     

PKC抑制剂灯盏花素乙对内脏炎症痛大鼠脊髓NO/cGMP信号转导系统的影响

目的探讨灯盏花素乙在甲醛复制的内脏炎症痛中的作用及其对NO/cGMP信号转导系统的影响。方法成年健康Wistar大鼠,随机分为4组:正常对照组、内脏炎症痛组、溶媒组和灯盏花素乙组。观察:①鞘内注射灯盏花素乙后大鼠行为学变化,以15min为一个时间段,共2h,计算疼痛分数;②致痛后30min取脊髓,用分光光度计法测定NOS活性、NO产量和放射免疫法测定cGMP含量。结果①灯盏花素乙组在前90min内疼痛分数低于内脏炎症痛组(P<0.05orP<0.01);②内脏炎症痛、溶媒和灯盏花素乙组脊髓的NOS活性、NO产量和cGMP含量均高于正常对照组(P<0.05orP<0.01),灯盏花素乙组低于内脏炎症痛组(P<0.01)。结论①灯盏花素乙能减轻甲醛复制的内脏炎症痛;②灯盏花素乙可能通过抑制脊髓内PKC的激活,进而抑制NO/cGMP信号转导系统的激活。     

Down-modulation through protein kinase C-α of lipopolysaccharide-induced expression of membrane CD14 in mouse bone marrow granulocytes

We have previously shown that stimulation of mouse bone marrow granulocytes (BMC) by lipopolysaccharide (LPS) induces the expression of CD14. We found here that phorbol 12-myristate 13-acetate (PMA) blocks this LPS effect. The aim of this study was to investigate the mechanism by which PMA can block the LPS signaling pathway in BMC. The unmodified binding of a radiolabeled LPS in PMA-treated cells indicated that the PMA effect was not the consequence of a shedding or an internalization of the LPS receptor, but was rather due to a biochemical event that follows the interaction of LPS with its receptor. The observations that a selective activator of protein kinase C (PKC)-α (sapintoxin D) mimics the PMA effect, whereas a selective PKC-α inhibitor (Ro-320432) antagonizes this effect, suggest a regulatory role of PKC-α in the LPS signaling pathway in mouse BMC.     

Protein Kinase C Theta Modulates PCMT1 through hnRNPL to Regulate FOXP3 Stability in Regulatory T Cells

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Modulation of atrial contraction by PKA and PKC during the compensated phase of eccentric cardiac hypertrophy

Abstract. Calcium homeostasis is intimately regulated by protein kinase phosphorylation cascades that are also involved in the induction and maintenance of cardiac hypertrophy. In addition, the development of cardiac hypertrophy has been associated with alteration in the activation of the adrenergic system. Therefore, we investigated the specific role of protein kinase A (PKA) and C (PKC) on cardiac muscle contractile activity in the presence and absence of adrenergic stimulation. Isolated left atrial preparations from sham– and volume overload–induced cardiac hypertrophied rats were superfused with Tyrode and electrically stimulated at 0.75 Hz. Contraction was assessed in the basal and pre–stimulated (norepinephrine, 10^–9M) states. Specific inhibitors, KT 5720 for PKA and Ro-32-0432 for PKC, were used. Peak tension development in left atria from sham–operated rats was more sensitive to PKC– than PKA–inhibition, whereas this differential sensitivity was abolished in the hypertrophied hearts. This difference was mainly due to an increase in the role of PKA in the contractile response. Developed peak tension by left atria from shunt rats was higher than that from sham rats, but when expressed to relative tissue mass, hypertrophied muscle showed weaker contraction than that from the sham group. In addition, the left atrial velocity of contraction in the sham is PKA–sensitive, while that of the shunt is PKC–sensitive. Furthermore, the velocity of relaxation shows dependency on both protein kinases, with PKC having a greater effect than PKA in the hypertrophied group. NE increased the PTD and the velocity of contraction (+dT/dt) through PKA and PKC dependent mechanisms, without affecting the velocity of relaxation (–dT/dt) in atrial muscle from sham rats. In contrast, during eccentric hypertrophy NE effectively reduced PTD as well as the –dT/dt through a PKC–dependent mechanism. The present study demonstrates that during early development of moderate eccentric cardiac hypertrophy there is: (1) a reduced specific peak tension developed due to an imbalance in the PKA and PKC activation; (2) a change in the protein kinase dependence of the velocity of contraction and relaxation from PKA to PKC with atrial hypertrophy; and (3) a negative inotropic response to adrenergic receptor stimulation. These functional responses may play a critical role in the cardiac performance during the progression of eccentric cardiac hypertrophy into the decompensated phase and heart failure.     

PKC/CPI-17通路对冠状动脉旁路移植术桥血管张力的影响

目的观察PKC/CPI-17通路对冠状动脉旁路移植术(CABG)中不同类型桥血管张力的影响,探讨其对糖尿病桥血管痉挛的作用。方法使用体外血管环灌流的方法,观察基础状态下及蛋白激酶C(PKC)激动剂(PMA)和抑制剂(Cal-C)灌流条件下,去甲肾上腺素(PE)和乙酰胆碱(Ach)介导的废弃桥血管张力的变化。比较糖尿病组和非糖尿病组桥血管上述张力变化,并以Western blot的方法评价两组患者桡动脉(RA)桥血管PKC、CPI-17蛋白表达的差异。结果 RA、大隐静脉(GSA)对PE收缩反应强于乳内动脉(IMA)(P0.01,P0.05);PMA使PE诱导的RA收缩作用增强,Cal-C使PE诱导的RA收缩作用减弱。糖尿病组RA对PE最大收缩反应[(3.78±0.62)g]明显强于非糖尿病组[(3.21±0.75)g,P0.05]。且糖尿病组RA和IMA中PKC、CPI-17蛋白表达显著上升(P0.05)。结论 PKC/CPI-17通路在CABG术桥血管痉挛中发挥重要作用,糖尿病通过影响该通路的表达影响桥血管痉挛。