FAS/TNF R1 INITIATED HEPATOCYTE DEATH IN MEDIATE BY BID

  • Yin, Xiao-Ming, (PI)

Project: Research project

Project Details

Description

Description: Programmed cell death, or apoptosis is a fundamental biological process in development and homeostasis control within all multicellular organisms. Disturbances in the regulation of apoptosis may result in diseases such as cancer or autoimmunity. The apoptosis pathways include components that are at the cell surface and serve as receptor molecules for death signals, such as Fas or TNF-receptor 1. The engagement of the death receptors leads to recruitment and subsequent activation of caspases, the central executors in the death pathway. However, other death signals, such as radiation and chemotherapeutic drugs may activate caspases by inducing release of cytochrome c from mitochondria. The mitochondrial pathway is susceptible to the regulation of Bcl-2 family proteins. The pro-apoptosis members of this family (Bid or Bax) can induce cytochrome c release, whereas the anti-apoptosis members of the family (Bcl-2 or Bcl-xL) can inhibit its release. Recently it has been shown that the cytosolic pathway initiated by Fas or TNF-R1 can be linked to the mitochondrial pathway via Bid, a pro-apoptosis member of the Bcl-2 family. More importantly, it seems that this connection plays a critical role in the development of hepatocyte apoptosis induced by Fas/TNF-R1 activation. The applicant has previously generated a bid-deficient animal model and thus intend to use this model to study: 1) the role of Bid in Fas/TNF-R1 -initiated hepatic injury in vivo; 2) the mitochondrial events induced by Bid in hepatocyte apoptosis; 3) the molecular mechanisms of Bid in regulating mitochondrial apoptotic events.
StatusFinished
Effective start/end date7/20/002/29/12

Funding

  • National Institutes of Health: $154,934.00
  • National Institutes of Health: $218,579.00
  • National Institutes of Health: $181,283.00
  • National Institutes of Health: $148,541.00
  • National Institutes of Health: $14,564.00
  • National Institutes of Health: $218,579.00
  • National Institutes of Health: $218,985.00
  • National Institutes of Health: $217,194.00
  • National Institutes of Health: $225,107.00
  • National Institutes of Health: $220,829.00
  • National Institutes of Health: $218,579.00
  • National Institutes of Health: $63,645.00

ASJC

  • Medicine(all)

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