Protection against necrosis but not apoptosis by heat-stress proteins in vascular smooth muscle cells evidence for distinct modes of cell death
Protection against necrosis but not apoptosis by heat-stress proteins in vascular smooth muscle cells evidence for distinct modes of cell death
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DOI：
10.1161/01.hyp.33.3.906
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发表时间：
1999-03-01
期刊：
影响因子：
8.3
通讯作者：
Tremblay, J
中科院分区：
文献类型：
--
作者：
Champagne, MJ;Dumas, P;Tremblay, J
我们以前曾报道，培养的血管平滑肌细胞（VSMC）分离自自发性高血压大鼠（SHR）显示较高的增殖和细胞死亡比正常血压对照组。除了保护细胞免受死亡外，热应激蛋白（HSP）似乎在细胞增殖中发挥作用。本研究探讨了HSP 72和HSP 27在SHR VSMC增殖和死亡中的作用。我们进行了详细的判别分析，以表征哪种类型的VSMC死亡是由热应激（HS）和血清剥夺，血清剥夺诱导的凋亡（caspase-3切割和DNA梯状）和继发性坏死，这2个过程是一个连续的对方。相反，急性HS（46 ℃，30分钟），抑制BN.lx和SHR VSMC增殖2倍，增加坏死（分别为5倍和2倍），但不凋亡。急性HS前6小时轻度HS（44 ℃，15分钟）诱导的VSMC中HSP 72和HSP 27表达阻止了增殖抑制和坏死诱导，对血清剥夺诱导的或星形孢菌素诱导的凋亡无影响。与BN.lx VSMC相比，这种诱导的HSP 72和HSP 27的表达并没有消除SHR VSMC的较高的基础增殖、凋亡和坏死，表明这些HSP不参与改变的SHR VSMC增殖和死亡。此外，虽然细胞凋亡和坏死可能是一个连续体，在VSMC中的2个过程可以区分为HS，其中只有坏死是由先前的HSP积累防止。
We have reported previously that cultured vascular smooth muscle cells (VSMC) isolated from spontaneously hypertensive rats (SHR) show higher proliferation and cell death than normotensive controls. In addition to protecting cells against death, heat stress proteins (HSPs) appear to play a role in cell proliferation. This investigation examines the involvement of HSP72 and HSP27 in altered SHR VSMC proliferation and death. We have performed detailed discriminatory analysis to characterize which type of VSMC death is induced by heat stress (HS) and serum deprivation, Serum deprivation induced apoptosis (caspase-3 cleavage and DNA laddering) and secondary necrosis, the 2 processes being a continuum of each other. Ln contrast, acute HS (46 degrees C, 30 minutes), which inhibited BN.lx and SHR VSMC proliferation by 2-fold, increased necrosis (by 5-fold and 2-fold, respectively) but not apoptosis. HSP72 and HSP27 expression evoked in VSMC by mild HS (44 degrees C, 15 minutes) 6 hours before acute HS prevented the inhibition of proliferation and induction of necrosis with no effect on serum deprivation-induced or staurosporine-induced apoptosis. This induced expression of HSP72 and HSP27 did not eliminate the higher basal proliferation, apoptosis, and necrosis of SHR VSMC compared with BN.lx VSMC, suggesting that these HSPs are not involved in altered SHR VSMC proliferation and death. Also, although apoptosis and necrosis may he a continuum, in VSMC the 2 processes may be distinguished by HS, in which only necrosis is prevented by prior HSP accumulation This observation may be of use in designing strategies for cellular protection.