Phosphatidylserine Translocase and Calcium Channels

磷脂酰丝氨酸转位酶和钙通道

基本信息

  • 批准号:
    6460322
  • 负责人:
  • 金额:
    $ 3.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-05-01 至 2004-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Chemotherapy causes apoptosis of brain tumor cells, which are then cleared through phagocytosis. In peripheral tissue, phagocytosis is preceded by a recognition process in which scavenger macrophages selectively bind to phosphatidylserine (PS) molecules that are exposed on the surface of the apoptotic cells. During the current granting period, the applicant's team has shown that PS plays a central role also in the recognition of apoptotic neurotumor cells by the resident scavenger cells of the brain, the microglia. The enzyme that plays a central role in the inner-membrane sequestering of PS in healthy cells is the aminophospholipid translocase (APTL), which is also a Mg2+-ATPase and belongs to a recently classified subfamily of P-type ATPase. It is highly expressed in the CNS, but its regulation and role in neurons are poorly understood. Its inhibition or down regulation results in the typical apoptotic feature of PS-externalization. In order to study the regulation profile of this enzyme, the mouse APTL cDNA was overexpressed from vector pCMV6 in the calcium channel-deficient hybrid neuroblastoma cells, HN2. In addition to showing a 15-fold increase in phosphatidylserine translocase activity, all the clones surprisingly displayed significant levels of voltage-gated calcium channels. Another cell line (HN2V32) that was prepared by stable expression of a heterologous gene also harbored in pCMV6, did not display any voltage-gated calcium current. The central goal of this renewal application is to characterize the proximal promoter of the APTL gene, and also understand the correlation between overexpressed APTL and the appearance of voltage-gated calcium channels. The proximal promoter sequence will be obtained using "Rapid Amplification of cDNA Ends" (5'-RACE) and S1 nuclease digestion analysis. Functional activity and sequence features of the promoter will be tested using serially deleted segments of the promoter sequence to drive expression of the chloramphenical acetyl transferase (CAT) reporter gene. Software analysis of the promoter sequence will reveal the presence of enhancer/repressor elements. Possible synergism between APTL and pCMV6 in the expression of the pore-forming alpha1 subunit of voltage-gated calcium channels will be tested by expressing APTL cDNA from a vector completely different from pCMV6 and then testing the APTL-overexpressing clones for the expression of alpha1 subunits. Possible cross talk between APTL and the alpha1 subunits will be tested by expressing epitope-tagged APTL and then testing the effect of APTL expression levels on the expression of calcium channel alpha1 subunits. Also, APTL expression will be suppressed by antisense treatment to look for its effect on the expression and activity of calcium channels. Results from this project will shed new light on the regulation and role of the protein APTL in brain neurons and apoptotic neurotumor cells.
描述(申请人提供):化疗引起脑细胞凋亡

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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PROBAL BANERJEE其他文献

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{{ truncateString('PROBAL BANERJEE', 18)}}的其他基金

A Chemical Strategy of Developing Resistance-Proof, Immune-Friendly Drugs
开发抗耐药性、免疫友好型药物的化学策略
  • 批准号:
    10113275
  • 财政年份:
    2021
  • 资助金额:
    $ 3.3万
  • 项目类别:
The 5-HT1A Receptor and Brain Development
5-HT1A 受体和大脑发育
  • 批准号:
    7445477
  • 财政年份:
    2007
  • 资助金额:
    $ 3.3万
  • 项目类别:
The 5-HT1A Receptor and Brain Development
5-HT1A 受体和大脑发育
  • 批准号:
    7487561
  • 财政年份:
    2006
  • 资助金额:
    $ 3.3万
  • 项目类别:
The 5-HT1A Receptor and Brain Development
5-HT1A 受体和大脑发育
  • 批准号:
    7253430
  • 财政年份:
    2006
  • 资助金额:
    $ 3.3万
  • 项目类别:
The 5-HT1A Receptor and Brain Development
5-HT1A 受体和大脑发育
  • 批准号:
    7144542
  • 财政年份:
    2006
  • 资助金额:
    $ 3.3万
  • 项目类别:
The 5-HT1A Receptor and Brain Development
5-HT1A 受体和大脑发育
  • 批准号:
    7120857
  • 财政年份:
    2005
  • 资助金额:
    $ 3.3万
  • 项目类别:
REGULATION OF APOPTOSIS BY THE SEROTONIN 1A RECEPTOR
5-羟色胺 1A 受体对细胞凋亡的调节
  • 批准号:
    2612538
  • 财政年份:
    1998
  • 资助金额:
    $ 3.3万
  • 项目类别:
Phosphatidylserine Translocase and Calcium Channels
磷脂酰丝氨酸转位酶和钙通道
  • 批准号:
    6747822
  • 财政年份:
    1998
  • 资助金额:
    $ 3.3万
  • 项目类别:
Regulation of ATPase II and Clearance of Cancer Cells
ATPase II 的调节和癌细胞的清除
  • 批准号:
    6944110
  • 财政年份:
    1998
  • 资助金额:
    $ 3.3万
  • 项目类别:
Phosphatidylserine Translocase and Calcium Channels
磷脂酰丝氨酸转位酶和钙通道
  • 批准号:
    6561733
  • 财政年份:
    1998
  • 资助金额:
    $ 3.3万
  • 项目类别:

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