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Free radical-dependent Ca2+ signaling: role of Ca2+-induced Ca2+ release
Antioxidants & Redox Signaling
|August 9, 2001
Summary
Free radicals initiate calcium release from scallop sarcoplasmic reticulum (SR). This release then triggers a calcium-induced calcium release (CICR) mechanism, amplifying the initial effect.
Area of Science:
- Biochemistry
- Cellular Physiology
- Muscle Contraction
Background:
- Free radicals can induce Ca2+ release from scallop sarcoplasmic reticulum (SR).
- The precise mechanism amplifying this initial Ca2+ release is not fully understood.
Purpose of the Study:
- To investigate the role of calcium-induced calcium release (CICR) in Fe3+/ascorbate-induced Ca2+ release from scallop SR.
- To elucidate the interplay between free radical production and subsequent Ca2+ release dynamics.
Main Methods:
- Scallop SR vesicles were incubated with the fluorescent Ca2+ indicator fluo-3.
- Exposure to Fe3+/ascorbate initiated Ca2+ release.
- Reactive oxygen species production was monitored using dihydrorhodamine and malondialdehyde assays.
- Specific inhibitors (Ruthenium red) and activators (cyclic adenosine 5'-diphosphoribose) were used to probe the Ca2+ release mechanism.
Main Results:
- Fe3+/ascorbate induced massive Ca2+ release from SR vesicles, peaking at 30 minutes.
- Oxyradical production was transient, lasting approximately 5 minutes, indicating Ca2+ release extended beyond free radical generation.
- Ruthenium red inhibited Ca2+ release, while cyclic adenosine 5'-diphosphoribose accelerated it, supporting a CICR mechanism.
Conclusions:
- Fe3+/ascorbate-induced Ca2+ release from scallop SR is initially mediated by free radicals.
- This initial release triggers a significant calcium-induced calcium release (CICR) cascade.
- CICR dramatically amplifies the Ca2+ release, explaining the prolonged release observed after free radical exhaustion.
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