Synergistic suppression of apoptosis in salivary acinar cells by IGF1 and EGF
Synergistic suppression of apoptosis in salivary acinar cells by IGF1 and EGF
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DOI：
10.1038/sj.cdd.4401153
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发表时间：
2003-03-01
影响因子：
12.4
通讯作者：
Anderson, SM
中科院分区：
文献类型：
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作者：
Limesand, KH;Barzen, KA;Anderson, SM
组织稳态需要平衡细胞增殖和程序性细胞死亡。在大鼠腮腺腺泡细胞（C5）中，通过半胱天冬酶3激活和细胞subG（1）DNA含量定量测定，lGF1显著抑制依托泊苷诱导的细胞凋亡。用腺病毒转导C5细胞，腺病毒表达Akt抑制的足叶乙甙诱导的细胞凋亡的组成性激活突变体，而Akt的激酶失活突变体抑制IGF1的保护作用。IGF1还抑制紫杉醇和布雷菲德菌素A诱导的细胞凋亡。EGF不能抑制依托泊苷诱导的细胞凋亡，但能够与IGFI协同作用，进一步抑制依托泊苷处理后的caspase 3激活和DNA切割。Akt的催化活性在用两种生长因子刺激后显著高于用单独的IGF 1或EGF刺激。这些结果表明，激活Akt的阈值是抑制细胞凋亡和生长因子在调节唾液腺稳态的协同作用所必需的。
Tissue homeostasis requires balancing cell proliferation and programmed cell death. lGF1 significantly suppressed etoposide-induced apoptosis, measured by caspase 3 activation and quantitation of cellular subG(1) DNA content, in rat parotid salivary acinar cells (C5). Transduction of C5 cells with an adenovirus expressing a constitutively activated mutant of Akt-suppressed etoposide-induced apoptosis, whereas a kinase-inactive mutant of Akt suppressed the protective effect of IGF1. IGF1 also suppressed apoptosis induced by taxol and brefeldin A. EGF was unable to suppress apoptosis induced by etoposide, but was able to synergize with IGFI to further suppress caspase 3 activation and DNA cleavage after etoposide treatment. The catalytic activity of Akt was significantly higher following stimulation with both growth factors compared to stimulation with lGF1 or EGF alone. These results suggest that a threshold of activated Akt is required for suppression of apoptosis and the cooperative action of growth factors in regulating salivary gland homeostasis.