Singh Ripudaman, Kølvraa Steen, Bross Peter, Jensen Uffe Birk, Gregersen Niels, Tan Qihua, Knudsen Christian, Rattan Suresh I S
Department of Human Genetics, University of Aarhus, Aarhus C, Denmark.
Cell Stress Chaperones. 2006 Autumn;11(3):208-15. doi: 10.1379/csc-184r.1.
Age-dependent changes in heat shock response (HSR) were studied in mononuclear cells (monocytes and lymphocytes) collected from young (mean age = 22.6 +/- 1.7 years) and middle-aged (mean age = 56.3 +/- 4.7 years) subjects after 1 hour of heat shock at 42 degrees C. Genotype-specific HSR was measured by genotyping the subjects for 3 single nucleotide polymorphisms, HSPA1A(A-110C), HSPA1B(A1267G), and HSPA1L(T2437C), 1 each in the 3 HSP70 genes. A significant age-related decrease in the induction of Hsp70 occurred after heat shock in both monocytes and lymphocytes. The noninducible and inducible forms of Hsp70 decreased 1.3-fold (P < 0.001) and 1.4-fold (P < 0.001), respectively, in the monocytes with age. In the young subjects, a positive association was found between HSPA1L(T2437C) polymorphism and HSR. CC carriers had a significantly lower induction than TT carriers in both monocytes (P = 0.015) and lymphocytes (P = 0.044). This polymorphism, which is present in the coding region of HSPA1L gene, can affect the chaperoning function of Hsp70. These data consolidate our other observations that the CC genotype is unfavorable for human longevity and provide a functional explanation in terms of variations in HSR.
研究了从年轻（平均年龄 = 22.6 ± 1.7岁）和中年（平均年龄 = 56.3 ± 4.7岁）受试者采集的单核细胞（单核细胞和淋巴细胞）在42℃热休克1小时后的热休克反应（HSR）的年龄依赖性变化。通过对受试者的3个单核苷酸多态性HSPA1A(A - 110C)、HSPA1B(A1267G)和HSPA1L(T2437C)进行基因分型来测量基因型特异性HSR，这3个多态性分别位于3个HSP70基因中。热休克后，单核细胞和淋巴细胞中Hsp70的诱导均出现与年龄相关的显著下降。随着年龄增长，单核细胞中Hsp70的非诱导型和诱导型分别下降了1.3倍（P < 0.001）和1.4倍（P < 0.001）。在年轻受试者中，发现HSPA1L(T2437C)多态性与HSR之间存在正相关。CC携带者在单核细胞（P = 0.015）和淋巴细胞（P = 0.044）中的诱导均显著低于TT携带者。这种存在于HSPA1L基因编码区的多态性可影响Hsp70的伴侣功能。这些数据巩固了我们的其他观察结果，即CC基因型不利于人类长寿，并从HSR的变化方面提供了功能解释。
