LITHIUM DELAYS THE RADIATION-INDUCED APOPTOTIC PROCESS IN EXTERNAL GRANULE CELLS OF MOUSE CEREBELLUM
LITHIUM DELAYS THE RADIATION-INDUCED APOPTOTIC PROCESS IN EXTERNAL GRANULE CELLS OF MOUSE CEREBELLUM
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DOI：
10.1269/jrr.36.203
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发表时间：
1995-09-01
影响因子：
2
通讯作者：
NAKANO, A
中科院分区：
文献类型：
--
作者：
INOUYE, M;YAMAMURA, H;NAKANO, A
发育中的小脑外颗粒层（EGL）的增殖细胞对电离辐射高度敏感。我们研究了锂，细胞内信号传导的抑制剂，对辐射诱导的细胞凋亡的表现的影响。将新生小鼠单独暴露于0.5戈伊γ-照射，或首先用锂（10 μ mol/g，SC）处理，然后在2小时后给予0.5戈伊照射。治疗后不同时间对EGL进行组织学检查以检测细胞凋亡。凋亡细胞迅速增加，照射后6小时达高峰（约14%），24小时逐渐下降至对照水平，预先用锂处理延迟了凋亡的出现，高峰出现在照射后12小时，死亡细胞的消失延迟了约1天。在整个大脑中的锂浓度迅速增加，在照射时为30微克/克，并保持在40微克/克以上40小时。据报道，锂抑制鸟嘌呤核苷酸结合G蛋白以及磷酸肌醇营业额。在辐射引起的各种损伤中，DNA双链断裂是细胞致死的最重要来源。然而，目前的研究结果表明，环AMP介导的和/或磷酸肌醇介导的信号系统调节辐射诱导的细胞凋亡。
Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 mu mol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 mu g/g at the time of irradiation and remaining at more than 40 mu g/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis.