González Beatriz, Manso Rafael
Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, E-28049 Cantoblanco, Madrid, Spain.
J Physiol. 2004 Apr 15;556(Pt 2):369-85. doi: 10.1113/jphysiol.2003.058420. Epub 2004 Jan 30.
Liver cells synthesize HSP72, the cytosolic highly stress-inducible member of the 70 kDa family of heat-shock proteins (HSP70s), in response to acute exercise. This study was aimed at obtaining further insight into the physiological relevance of the hepatic stress response to exercise by investigating the induction and long-term maintenance of increased levels of HSP70s of the HSP and glucose-regulated protein (GRP) families, their post-translational modifications during or after exercise and the possible relation of HSP induction to oxidative stress. In a running rat model, acute exercise activated the synthesis and accumulation of HSP72, GRP75 and GRP78 in liver cells, pointing towards a multifactorial origin of this response. A peak HSP72 accumulation was observed shortly after exercise as a result of transcriptional activation. HSP72 was reduced shortly after exercise preceding the disappearance of its mRNA. Two further waves of HSP72 accumulation peaked 8 and 48 h after exercise without transcriptional activation. A transient increase in the proportion of acidic variants of HSP72 and HSP73 was also observed shortly after exercise as a result, at least in part, of protein phosphorylation. Free and protein-bound lipid peroxidation derivatives (TBARS) showed a tendency to increase in the early post-exercise and the free-to-protein-bound TBARS ratio decreased significantly after 2 h. During the early post-exercise period, protein-bound TBARS correlated positively with HSP72 and 73, but not with GRP75 or GRP78. Altogether, the reported results indicate that the early induction and post-translational modification of HSP70s in liver cells following exercise is a preliminary step of a series of long-lasting HSP70-related events, possibly designed to preserve liver cell homeostasis and to help provide a concerted response of the whole organism to physical stress.
肝细胞会响应急性运动而合成热休克蛋白72(HSP72),它是70 kDa热休克蛋白家族(HSP70s)中胞质内高度应激诱导的成员。本研究旨在通过调查HSP和葡萄糖调节蛋白(GRP)家族中HSP70s水平升高的诱导和长期维持情况、运动期间或运动后它们的翻译后修饰以及HSP诱导与氧化应激的可能关系,进一步深入了解肝脏对运动应激反应的生理相关性。在一个跑步大鼠模型中,急性运动激活了肝细胞中HSP72、GRP75和GRP78的合成与积累,表明这种反应具有多因素起源。运动后不久,由于转录激活,观察到HSP72积累达到峰值。运动后不久,HSP72在其mRNA消失之前就有所减少。另外两波HSP72积累在运动后8小时和48小时达到峰值,且没有转录激活。运动后不久,还观察到HSP72和HSP73酸性变体的比例短暂增加,这至少部分是由于蛋白质磷酸化所致。游离和与蛋白质结合的脂质过氧化衍生物(TBARS)在运动后的早期有增加的趋势,2小时后游离与蛋白质结合的TBARS比值显著下降。在运动后的早期,与蛋白质结合的TBARS与HSP72和73呈正相关,但与GRP75或GRP78无关。总之,报告的结果表明,运动后肝细胞中HSP70s的早期诱导和翻译后修饰是一系列与HSP70相关的长期事件的初步步骤,可能旨在维持肝细胞内稳态,并帮助整个机体对身体应激做出协同反应。