Angiotensin II type 2 receptor mediates programmed cell death.
Angiotensin II type 2 receptor mediates programmed cell death.
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DOI：
10.1073/pnas.93.1.156
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发表时间：
1996-01
影响因子：
11.1
通讯作者：
T. Yamada;M. Horiuchi;V. Dzau
中科院分区：
文献类型：
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作者：
T. Yamada;M. Horiuchi;V. Dzau
最近发现的血管紧张素II 2型(AT2)受体的功能仍然难以捉摸。该受体在胎儿中大量表达，但在成人组织中除脑、肾上腺髓质和闭锁卵巢外几乎不表达。在这项研究中，我们证明了这种受体介导了细胞程序性死亡(细胞凋亡)。我们在PC12W细胞(大鼠嗜铬细胞瘤细胞系)和R3T3细胞(小鼠成纤维细胞系)中观察到了这种作用，这两种细胞表达丰富的AT2受体，但不表达AT1受体。其细胞机制似乎涉及丝裂原激活的蛋白激酶(MAP)的去磷酸化。蛋白酪氨酸磷酸酶抑制剂钒酸可减弱AT2受体对MAP激酶的去磷酸化作用，恢复细胞的凋亡变化。MAP激酶磷酸酶1反义寡核苷酸抑制AT2受体介导的MAP激酶去磷酸化，阻断AT2受体介导的细胞凋亡。这些结果表明，蛋白酪氨酸磷酸酶，包括由AT2受体激活的MAP激酶磷酸酶1，参与了细胞凋亡。我们推测AT2受体的这种凋亡功能可能在发育生物学和病理生理学中发挥重要作用。
The function of the recently discovered angiotensin II type 2 (AT2) receptor remains elusive. This receptor is expressed abundantly in fetus, but scantily in adult tissues except brain, adrenal medulla, and atretic ovary. In this study, we demonstrated that this receptor mediates programmed cell death (apoptosis). We observed this effect in PC12W cells (rat pheochromocytoma cell line) and R3T3 cells (mouse fibroblast cell line), which express abundant AT2 receptor but not AT1 receptor. The cellular mechanism appears to involve the dephosphorylation of mitogen-activated protein kinase (MAP kinase). Vanadate, a protein-tyrosine-phosphatase inhibitor, attenuated the dephosphorylation of MAP kinases by the AT2 receptor and restored the apoptotic changes. Antisense oligonucleotide to MAP kinase phosphatase 1 inhibited the AT2 receptor-mediated MAP kinase dephosphorylation and blocked the AT2 receptor-mediated apoptosis. These results suggest that protein-tyrosine-phosphatase, including MAP kinase phosphatase 1 activated by the AT2 receptor, is involved in apoptosis. We hypothesize that this apoptotic function of the AT2 receptor may play an important role in developmental biology and pathophysiology.