GADD34 inhibits activation-induced apoptosis of macrophages through enhancement of autophagy.
GADD34 inhibits activation-induced apoptosis of macrophages through enhancement of autophagy.
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DOI：
10.1038/srep08327
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发表时间：
2015-02-09
影响因子：
4.6
通讯作者：
Isobe K
中科院分区：
文献类型：
--
作者：
Ito S;Tanaka Y;Oshino R;Aiba K;Thanasegaran S;Nishio N;Isobe K
自噬是所有真核生物共同的生理功能。这一过程是由包括氨基酸在内的营养素的消耗引起的。GADD 34在DNA损伤、ER应激和氨基酸剥夺后表达。在这里，我们研究了GADD 34对巨噬细胞自噬和细胞活化的影响。剥夺酪氨酸和半胱氨酸可显著诱导巨噬细胞GADD 34的表达。LPS刺激结合酪氨酸/半胱氨酸剥夺最初激活巨噬细胞，但随后在刺激的后期转变为细胞死亡。当LPS刺激结合酪氨酸/半胱氨酸剥夺时，GADD 34的缺陷增强了细胞活化信号，如Src家族，Erk 1/2，p38 MAPK和Akt。在刺激的后期，GADD 34的缺乏增加了细胞凋亡比野生型巨噬细胞。此外，我们发现，与野生型细胞相比，当细胞被LPS联合酪氨酸/半胱氨酸剥夺处理时，GADD 34缺陷型巨噬细胞中的mTOR-S6 K信号转导高度增强。结合酪氨酸/半胱氨酸剥夺的LPS刺激增加LC 3-II。与野生型巨噬细胞相比，缺陷GADD 34减少了LPS刺激和酪氨酸/半胱氨酸剥夺诱导的LC 3-II和自噬体形成。这些结果表明，GADD 34通过调节巨噬细胞中的mTOR信号通路增强自噬并抑制由LPS联合氨基酸剥夺刺激的凋亡。
Autophagy is a common physiological function in all eukaryotes. The process is induced by depletion of nutrients including amino acids. GADD34 is expressed following DNA damage, ER stresses and amino acid deprivation. Here, we investigated the effects of GADD34 on autophagy and cell activation in macrophages. The deprivation of tyrosine and cysteine markedly induced the expression of GADD34 in macrophages. LPS stimulation combined with tyrosine/cysteine-deprivation initially activated macrophages, but then shifted to cell death in late phase of stimulation. When LPS stimulation was combined with tyrosine/cysteine-deprivation, a deficiency of GADD34 enhanced cell activation signaling such as Src-family, Erk1/2, p38 MAPK and Akt. In the late phase of stimulation, a deficiency of GADD34 increased apoptosis more than that in wild-type macrophages. Further we found that mTOR-S6K signaling was highly enhanced in GADD34-deficient macrophages compared with wild-type cells when cells were treated by LPS combined with tyrosine/cysteine-deprivation. LC3-II was increased by LPS stimulation combined with tyrosine/cysteine-deprivation. Defective GADD34 reduced LC3-II and autophagosome formation induced by LPS-stimulation and tyrosine/cysteine-deprivation compared with that seen in wild-type macrophages. These results indicates that GADD34 enhances autophagy and suppresses apoptosis stimulated by LPS combined with amino acid deprivation through regulation of mTOR signaling pathway in macrophages.
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用电子显微镜研究的新生小鼠肾脏中的细胞分化。
DOI：
10.1083/jcb.3.3.349
发表时间：
1957-05-25
期刊：
The Journal of biophysical and biochemical cytology
影响因子：
--
作者：
CLARK SL Jr
通讯作者：
CLARK SL Jr
影响因子：
64.5
作者：
Demetriades C;Doumpas N;Teleman AA
通讯作者：
Teleman AA
影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
4.8
作者：
Hollander, MC;Zhan, QM;Fornace, AJ
通讯作者：
Fornace, AJ
影响因子：
4.8
作者：
Thiaville, Michelle M.;Pan, Yuan-Xiang;Kilberg, Michael S.
通讯作者：
Kilberg, Michael S.