Related Experiment Videos
Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death
S Blackshaw1, A Sawa, A H Sharp
1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Summary
Type 3 inositol trisphosphate receptors (IP(3)R3) play a key role in programmed cell death (apoptosis). Increased IP(3)R3 levels are observed across diverse tissues undergoing apoptosis, suggesting a broad involvement in cell death mechanisms.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- The cellular mechanisms of calcium entry regulating cell proliferation and apoptosis remain unclear.
- Previous research indicated selective augmentation of type 3 inositol (1,4,5) trisphosphate receptors (IP(3)R3) in lymphocytes during programmed cell death.
Purpose of the Study:
- To investigate the role of IP(3)R3 in various apoptotic paradigms across different tissues.
- To determine if IP(3)R3 augmentation is a common feature of apoptosis.
Main Methods:
- Analysis of IP(3)R3 mRNA and protein levels in diverse apoptotic models.
- Utilizing antisense oligonucleotides to inhibit IP(3)R3 function in specific cell types.
Main Results:
- IP(3)R3 mRNA and protein levels were found to increase in multiple tissues undergoing apoptosis, including cerebellar granule cells, dorsal root ganglia, hair follicles, and intestinal villi.
- Elevated IP(3)R3 levels were also observed in neurotoxic damage induced by kainate.
- In chick dorsal root ganglia neurons, antisense inhibition of IP(3)R3 selectively prevented nerve growth factor deprivation-induced apoptosis.
Conclusions:
- Type 3 inositol trisphosphate receptors (IP(3)R3) are actively involved in the process of cell death (apoptosis).
- The augmentation of IP(3)R3 is a conserved mechanism observed in diverse tissues during apoptosis.