Whitlock N Andrew, Lindsey Kristie, Agarwal Neeraj, Crosson Craig E, Ma Jian-Xing
Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC 29425, USA.
Invest Ophthalmol Vis Sci. 2005 Mar;46(3):1085-91. doi: 10.1167/iovs.04-0042.
Hsp27 is a well-characterized and studied antiapoptotic protein. A recent study reported that Hsp27 is upregulated in the retina after retinal ischemic preconditioning. The timing of this upregulation of Hsp27 correlates with the protective effects of the treatment. It was the goal of the current study to determine what role Hsp27 plays in this protection.
The rat homologue of Hsp27 (rHsp27) was overexpressed in a transformed rat retinal ganglion cell line and subjected to ischemic stress and calcium overload.
The overexpression of rHsp27 increased cell survival and inhibited caspase-3 activation. However, the inhibition of caspase-3 alone had no effect on cell survival. Proteomic analysis after Ca(2+) overload identified four proteins that were repeatedly associated with rHsp27. These proteins include actin, Hsp70, eEF-1alpha, and SPIN-2. No association with cytochrome c or any caspase enzymes was detected.
The results indicate that Hsp27 protects the retinal cells by both caspase-dependent and -independent mechanisms.
热休克蛋白27（Hsp27）是一种已被充分表征和研究的抗凋亡蛋白。最近一项研究报道，视网膜缺血预处理后视网膜中Hsp27表达上调。Hsp27这种上调的时间与该治疗的保护作用相关。本研究的目的是确定Hsp27在这种保护作用中发挥何种作用。
在一种转化的大鼠视网膜神经节细胞系中过表达Hsp27的大鼠同源物（rHsp27），并使其遭受缺血应激和钙超载。
rHsp27的过表达提高了细胞存活率并抑制了半胱天冬酶 - 3的激活。然而，单独抑制半胱天冬酶 - 3对细胞存活没有影响。钙超载后的蛋白质组学分析鉴定出四种与rHsp27反复相关的蛋白质。这些蛋白质包括肌动蛋白、Hsp70、真核生物延伸因子 - 1α和SPIN - 2。未检测到与细胞色素c或任何半胱天冬酶的关联。
结果表明，Hsp27通过半胱天冬酶依赖性和非依赖性机制保护视网膜细胞。
