Induction of locomotor behavior in the giant African snail,Achatina fulica

• 1.1. The locomotor-inducting factor of the giant African snail, Achatina fulica, was examined.
• 2.2. Snails showed nocturnal circadian behavior in relative humidity at least over 50%. Although the rhythmicity was independent of light and darkness, it was disturbed easily by hydration, and hydrated snails continued to locomote throughout the day. For induction of locomotor behavior, relative humidity over 50% was the fundamental factor and water is shown to be the limiting factor for the endogeneous circadian oscillator.
• 3.3. The integument of snails showed a higher water permeability. Through the integument, hemolymph osmolality changed easily according to hydration and dehydration from about 120 to 400 mOsm/kg H₂O. Circadian behavior was induced in snails in which hemolymph osmolality ranged from about 130 to 230 mOsm/kg H₂O.
• 4.4. By hydration, hemolymph osmolality in quiescent and estivated snails which have higher osmolality decreased gradually and then they began to locomote according to the degree of dilution, and vice versa. The induction of behavior in these snails was controlled by low hemolymph osmolality.
• 5.5. Together with the endogeneous rhythmicity, water environment was shown to be the key factor for the induction of locomotor behavior.
• 6.6. Based on these results, the mechanisms of the induction of locomotor behavior in terrestrial pulmonates are proposed.

     

Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome

Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.     

模拟失重大鼠心肌与血管组织的热应激诱导HSP70表达

为研究模拟失重是否可以引起大鼠心肌与血管组织HSP70的诱导表达发生改变,用尾部悬吊大鼠模型模拟失重,以研究失重对生理的影响,用Northern杂交与Western印迹分析检测4周模拟失重大鼠热应激后并在室温下恢复1h(SUS-H1)或2h(SUS-H2_心肌,血管组织HSP70表达的变化,结果表明,热应激后,各组大鼠心肌组织的HSP72 mRNA表达的均显著增加,但SUS－H2大鼠心肌组织的表达显著低于CON－H2组;各组大鼠心肌组织HSP72表达也均显著增加,但SUS－H1与SUS－H2大鼠的表达与相应对照组相比,则仅呈降低趋势,其底动脉血管组织的HSP72 mRNA与HSP72诱导表达均显著增高,而在股动脉则两者仅呈降低趋势,上述结果提示,模拟失重可导致大鼠心肌发生类似衰老的心肌改变;身体前,后部血管组织HSP70的诱导表达变化可能与血管的分化性适应方向一致。     

Hsp70, a messenger from hyperthermia for the immune system

Heat shock proteins (Hsps) hold a dual role depending on their location. Inside cells, they fulfill essential survival functions as molecular chaperones forming complexes with intracellular polypeptides (self or foreign) to help in protein folding, the resolution of protein aggregates and intracellular protein transport. Released from the cell, they act as messengers communicating the cells’ interior protein composition to the immune system for initiation of immune responses against intracellular proteins. Here we describe the mechanisms by which Hsp70, the heat-inducible Hsp70 family member, crosstalks with the immune system. Further, we discuss that clinical hyperthermia could be a way to initiate the immunologic activity of Hsp70 by upregulating its expression and facilitating release through local necrosis.     

Crystal structure of the nucleotide‐binding domain of mortalin,the mitochondrial Hsp70 chaperone

Mortalin, a member of the Hsp70‐family of molecular chaperones, functions in a variety of processes including mitochondrial protein import and quality control, Fe‐S cluster protein biogenesis, mitochondrial homeostasis, and regulation of p53. Mortalin is implicated in regulation of apoptosis, cell stress response, neurodegeneration, and cancer and is a target of the antitumor compound MKT‐077. Like other Hsp70‐family members, Mortalin consists of a nucleotide‐binding domain (NBD) and a substrate‐binding domain. We determined the crystal structure of the NBD of human Mortalin at 2.8 Å resolution. Although the Mortalin nucleotide‐binding pocket is highly conserved relative to other Hsp70 family members, we find that its nucleotide affinity is weaker than that of Hsc70. A Parkinson's disease‐associated mutation is located on the Mortalin‐NBD surface and may contribute to Mortalin aggregation. We present structure‐based models for how the Mortalin‐NBD may interact with the nucleotide exchange factor GrpEL1, with p53, and with MKT‐077. Our structure may contribute to the understanding of disease‐associated Mortalin mutations and to improved Mortalin‐targeting antitumor compounds.     

Serum level of soluble Hsp70 is associated with vascular calcification

It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima–media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer’s kits. Fetuin-a levels were measured by radial immunodiffusion. Patients’ median age was 64 (57–71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156–4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021–5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.     

Hsp70与汉滩病毒S基因融合蛋白的原核表达及免疫小鼠的初步研究

本文构建了hsp70与S基因的原核融合表达载体pGEX-4T-1/hsp70-S,在大肠杆菌中表达,并通过GSTrapFF柱进行了纯化。同时制备了NP和Hsp70两种纯化蛋白。分别用这三种纯化蛋白免疫BALB/c小鼠,结果表明纯化的NP和Hsp70-NP两种蛋白均可同时诱导产生抗汉滩病毒核蛋白(NP)抗体,且后者刺激产生的抗体效价明显高于前者。淋巴细胞增殖实验表明,两组免疫小鼠的脾细胞均能够对体外抗原刺激产生增殖反应,而Hsp70-NP组免疫小鼠脾细胞对NP的增殖指数明显高于NP组免疫组。结果显示,与单独用NP免疫小鼠相比,Hsp70-NP纯化蛋白可以刺激机体产生更强的抗汉滩病毒体液免疫应答和特异性淋巴细胞增殖反应。     

Hsp70与汉滩病毒S基因融合蛋白的原核表达及免疫小鼠的初步研究

本文构建了hsp70与S基因的原核融合表达载体pGEX-4T-1/hsp70-S,在大肠杆菌中表达,并通过GSTrapFF柱进行了纯化.同时制备了NP和Hsp70两种纯化蛋白.分别用这三种纯化蛋白免疫BALB/c小鼠,结果表明纯化的NP和Hsp70-NP两种蛋白均可同时诱导产生抗汉滩病毒核蛋白(NP)抗体,且后者刺激产生的抗体效价明显高于前者.淋巴细胞增殖实验表明,两组免疫小鼠的脾细胞均能够对体外抗原刺激产生增殖反应,而Hsp70-NP组免疫小鼠脾细胞对NP的增殖指数明显高于NP组免疫组.结果显示,与单独用NP免疫小鼠相比,Hsp70-NP纯化蛋白可以刺激机体产生更强的抗汉滩病毒体液免疫应答和特异性淋巴细胞增殖反应.     

Hsp70-NP融合蛋白增强诱导HTNV NP特异性CTL的实验研究

本文采用纯化蛋白Hsp70-NP,NP,Hsp70分别免疫C57/BL6小鼠,取各组小鼠脾淋巴细胞进行淋巴细胞增殖试验和细胞毒试验。此外,为了获得细胞毒实验的靶细胞,本文还采用脂质体介导质粒pcDNA3.1/S转染黑色素瘤细胞B16,通过G418筛选稳定克隆,并用RT-PCR,Westernblots以及免疫荧光染色证实N蛋白在胞浆中表达。淋巴细胞增殖实验表明,Hsp70-NP,NP组小鼠脾淋巴细胞均能够对体外抗原刺激产生增殖反应,而Hsp70-NP组的增殖指数明显高于NP免疫组。细胞毒实验结果表明,LDH的释放具有效应细胞依赖性,Hsp70-NP,NP免疫组脾淋巴细胞均可以特异性杀伤靶细胞B16-N,而Hsp70-NP免疫组的杀伤率显著高于NP免疫组。实验结果显示,Hsp70可以增强NP诱导产生特异性CTL的能力。本研究结果为进一步设计基于NP的合成肽疫苗或基因疫苗提供了重要实验依据。     

Hsp70-NP融合蛋白增强诱导HTNV NP特异性CTL的实验研究

本文采用纯化蛋白Hsp70-NP,NP,Hsp70分别免疫C57/BL6小鼠,取各组小鼠脾淋巴细胞进行淋巴细胞增殖试验和细胞毒试验.此外,为了获得细胞毒实验的靶细胞,本文还采用脂质体介导质粒pcDNA3.1/S转染黑色素瘤细胞B16,通过G418筛选稳定克隆,并用RT-PCR,Western blots以及免疫荧光染色证实N蛋白在胞浆中表达.淋巴细胞增殖实验表明,Hsp70-NP,NP组小鼠脾淋巴细胞均能够对体外抗原刺激产生增殖反应,而Hsp70-NP组的增殖指数明显高于NP免疫组.细胞毒实验结果表明,LDH的释放具有效应细胞依赖性,Hsp70-NP,NP免疫组脾淋巴细胞均可以特异性杀伤靶细胞B16-N,而Hsp70-NP免疫组的杀伤率显著高于NP免疫组.实验结果显示,Hsp70可以增强NP诱导产生特异性CTL的能力.本研究结果为进一步设计基于NP的合成肽疫苗或基因疫苗提供了重要实验依据.     

Cytosolic Hsp70s are involved in the transport of aminopeptidase 1 from the cytoplasm into the vacuole

Eukaryotic 70 kDa heat shock proteins (Hsp70s) are localized in various cellular compartments and exhibit functions such as protein translocation across membranes, protein folding and assembly. Here we demonstrate that the constitutively expressed members of the yeast cytoplasmic Ssa subfamily, Ssa1/2p, are involved in the transport of the vacuolar hydrolase aminopeptidase 1 from the cytoplasm into the vacuole. The Ssap family members displayed overlapping functions in the transport of aminopeptidase 1. In SSAI and SSAII deletion mutants the precursor of aminopeptidase 1 accumulated in a dodecameric complex that is packaged in prevacuolar transport vesicles. Ssa1/2p was prominently localized to the vacuolar membrane, consistent with the role we propose for Ssa proteins in the fusion of transport vesicles with the vacuolar membrane.     

Geldanamycin induces Hsp70 and prevents alpha-synuclein aggregation and toxicity in vitro

Geldanamycin (GA) is a naturally occurring benzoquinone ansamycin that induces heat shock protein 70 (Hsp70). GA has been shown to reduce alpha-synuclein induced neurotoxicity in a fly model of Parkinson's disease. We have previously shown that heat shock proteins can prevent alpha-synuclein aggregation and protect against alpha-synuclein induced toxicity in human H4 neuroglioma cells. Here, we hypothesize that GA treatment will reduce alpha-synuclein aggregation and prevent alpha-synuclein induced toxicity and we show that GA can induce Hsp70 in a time- and concentration-dependent manner in H4 cells. Pretreatment with 200nM GA 24h prior to transfection prevented alpha-synuclein aggregation and protected against toxicity. Treatment of cells with pre-existing inclusions with GA did not result in a reduction in the number of cells containing inclusions, suggesting that upregulation of Hsp70 is not sufficient to remove established inclusions. Similarly, Western blot analysis demonstrated that GA treatment could dramatically reduce both total alpha-synuclein and high molecular weight alpha-synuclein aggregates. Taken together, these data suggest that GA is effective in preventing alpha-synuclein aggregation and may represent a pharmacological intervention to therapeutically increase expression of molecular chaperone proteins to treat neurodegenerative diseases where aggregation is central to the pathogenesis.     

Interacting contribution of the five polymorphisms in three genes of Hsp70 family to essential hypertension in Uygur ethnicity

Experimental evidence suggesting that heat shock protein 70 (Hsp70) gene or associated genes are responsible for the pathophysiology of hypertension is accumulating. In this study, we focused on five polymorphisms in three genes (HSPA1A, HSPA1B, and HSPA1L) of Hsp70 family to explore the genetic contribution, alone and in combination, of these polymorphisms to essential hypertension risk in a Uygur population. Genotyping was performed using PCR-RFLP and direct sequencing techniques. Data were analyzed using haplotype and multifactor dimensionality reduction (MDR) methods. Genotype distributions of all the polymorphisms satisfied the Hardy–Weinberg proportions in cases and controls. Statistical significance was only observed in the genotype (P = 0.0028) and (P = 0.0146) allele distributions of −110A/C polymorphism, with the −110C allele conferring a 1.45- and 2.83-fold of relative risk, assuming the additive and recessive models, respectively, and in 1267A/G genotype distribution (P = 0.0106) with the 1267G allele conferring a 44% reduced risk. The interaction information analysis indicated that polymorphisms −110A/C and 1267A/G had a strong synergistic effect, while polymorphisms 2074G/C and 2437T/C had a moderate synergistic effect. Haplotype analyses further strengthened the interaction information. Using the haplotype H₁ as a reference, haplotype H₄ had a 40% reduced risk, while haplotypes H₅ and H₈ had a significantly 5.00- and 3.75-fold increased risk for essential hypertension, respectively. Taken together, our results supported strong genetic interaction of the studied polymorphisms with the risk of having essential hypertension in Uygur ethnicity. Functional studies are warranted to confirm or refute these findings. This is the first study to evaluate the genetic interaction information of the Hsp70 in Uygur ethnicity, which represents one of the major nationalities in China with high homogeneity and unique lifestyles. Moreover, we employed the haplotype and MDR methods to explore the potential interaction of Hsp70 genetic polymorphisms in the pathogenesis of essential hypertension in Uygur.     

Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values

To facilitate the identification of candidate molecular biomarkers that are linked to the pathogenesis of hepatocellular carcinoma (HCC), we investigated protein-expression profiles of 146 tissue specimens including 67 pairs of tumors and adjacent non-tumors resected from HCC patients as well as 12 normal livers by 2-DE. Among the 1800 spots displayed in the liver proteome, a total of 90 protein species were found to be significantly different between the three groups (P < 0.05). Three of the top candidate markers up-regulated in HCC, with high receiver operating characteristic (ROC) curves, were identified by MS/MS analysis and belonged to the chaperone members: heat-shock protein (Hsp)27, Hsp70 and glucose-regulated protein (GRP)78. Over-expression of these chaperone proteins in HCC tissues was confirmed by Western blotting and immunohistochemistry. In correlation with clinico-pathological parameters, expression of Hsp27 was linked to alpha-fetoprotein level (P = 0.007) whereas up-regulation of GRP78 was associated with tumor venous infiltration (P = 0.035). No significant association of Hsp70 with any pathologic features was observed. The present HCC proteome analysis revealed that in response to the stressful cancerous microenvironment, tumor cells strived to increase the expression of chaperone proteins for cyto-protective function and to enhance tumor growth and metastasis.     

热休克蛋白70在心血管疾病中的保护作用

热休克蛋白(heat shock protein70,HSP70)是HSP家族中重要成员,在生物细胞中含量最高,可诱导性最强,具有保护细胞免受刺激损伤,促进受损细胞修复及抗炎、抗凋亡、耐受缺血/缺氧损伤等多种生物学功能。许多研究发现在心肌组织中HSP70表达升高可减轻心肌细胞损伤程度,利于损伤心肌细胞的恢复,在预防和延缓心血管疾病中起到重要作用。因此,热休克蛋白70诱导剂在心血管疾病的防治中具有潜在的临床价值。本文主要对HSP70在心血管疾病中的保护作用进行综述。     

Complex patterns of geographic variation in heat tolerance and Hsp70 expression levels in the common frog Rana temporaria

1.

We tested for geographical variation in heat tolerance and Hsp70 expression levels of Rana temporaria tadpoles along a 1500 km long latitudinal gradient in Sweden.     

Heat and exercise acclimation increases intracellular levels of Hsp72 and inhibits exercise-induced increase in intracellular and plasma Hsp72 in humans

In order to verify the effects of heat and exercise acclimation (HA) on resting and exercise-induced expression of plasma and leukocyte heat shock protein 72 (Hsp72) in humans, nine healthy young male volunteers (25.0 ± 0.7 years; 80.5 ± 2.0 kg; 180 ± 2 cm, mean ± SE) exercised for 60 min in a hot, dry environment (40 ± 0°C and 45 ± 0% relative humidity) for 11 days. The protocol consisted of running on a treadmill using a controlled hyperthermia technique in which the work rate was adjusted to elevate the rectal temperature by 1°C in 30 min and maintain it elevated for another 30 min. Before and after the HA, the volunteers performed a heat stress test (HST) at 50% of their individual maximal power output for 90 min in the same environment. Blood was drawn before (REST), immediately after (POST) and 1 h after (1 h POST) HST, and plasma and leukocytes were separated and stored. Subjects showed expected adaptations to HA: reduced exercise rectal and mean skin temperatures and heart rate, and augmented sweat rate and exercise tolerance. In HST1, plasma Hsp72 increased from REST to POST and then returned to resting values 1 h POST (REST: 1.11 ± 0.07, POST: 1.48 ± 0.10, 1 h POST: 1.22 ± 0.11 ng mL⁻¹; p < 0.05). In HST2, there was no change in plasma Hsp72 (REST: 0.94 ± 0.08, POST: 1.20 ± 0.15, 1 h POST: 1.17 ± 0.16 ng mL⁻¹; p > 0.05). HA increased resting levels of intracellular Hsp72 (HST1: 1 ± 0.02 and HST2: 4.2 ± 1.2 density units, p < 0.05). Exercise-induced increased intracellular Hsp72 expression was observed on HST1 (HST1: REST, 1 ± 0.02 vs. POST, 2.9 ± 0.9 density units, mean ± SE, p < 0.05) but was inhibited on HST2 (HST2: REST, 4.2 ± 1.2 vs. POST, 4.4 ± 1.1 density units, p > 0.05). Regression analysis showed that the lower the pre-exercise expression of intracellular Hsp72, the higher the exercise-induced increase (R = −0.85, p < 0.05). In conclusion, HA increased resting leukocyte Hsp72 levels and inhibited exercise-induced expression. This intracellular adaptation probably induces thermotolerance. In addition, the non-increase in plasma Hsp72 after HA may be related to lower stress at the cellular level in the acclimated individuals.     

Critical role of TRIF and MyD88 in Mycobacterium tuberculosis Hsp70-mediated activation of dendritic cells

As a potent immune regulator, heat shock protein 70 derived from Mycobacterium tuberculosis (Mtb Hsp70) has adjuvant effect and activates immune cells such as macrophages and dendritic cells (DCs). Although Toll-like receptors (TLRs) are known to involve in DCs activation by Mtb Hsp70, there is still a controversy and the underlying mechanism is not well understood. In this study, we examined whether TRIF and MyD88, the core adaptor molecules for TLRs signaling, regulate Mtb Hsp70-induced DCs activation. Although Mtb Hsp70 produced substantial level of cytokines (IL-6, IL-12p40, and TNF-α) in TRIF-deficient DCs in a dose-dependent manner, each level was significantly lower than that in WT cells. The cytokines production was almost abolished in MyD88-deficient DCs. Consistent with cytokine results, Mtb Hsp70-induced activation of NF-κB and MAPKs was also impaired in both TRIF- and MyD88-deficient DCs, as compared with WT cells. Inhibitor assay revealed that NF-κB, ERK, and JNK, but not p38, regulate Mtb Hsp70-induced production of cytokines. In addition, the up-regulation of co-stimulatory molecules and MHC class II was mostly TRIF-dependent in DCs in response Mtb Hsp70, whereas MyD88 was only partially involved. Finally, mixed leukocytes reaction (MLR) assay revealed that both TRIF and MyD88 are critical for DCs ability promoted by Mtb Hsp70 to differentiate naïve T cells into effector T cells of producing IFN-γ. Our findings suggest that both TRIF and MyD88 are essential for the activation and maturation of DCs in response to Mtb Hsp70.     

Dynamic expression of Hsp27 in the presence of mutant ataxin-3

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations. The molecular mechanisms underlying the selective neuronal death typical of MJD/SCA3 are unknown. In this study, human SK-N-SH neuroblastoma cells stably transfected with full-length MJD with 78 CAG repeats were assayed for the dynamic expression of Hsp27, known as a suppressor of poly-Q mediated cell death, in the presence of mutant ataxin-3 in different passages of cultured cells. A dramatic decrease of Hsp27 expression was observed in the earlier passage of cultured SK-N-SH-MJD78 cells, however, the later passage of cells showed a significant increase of Hsp27 to almost the same level of the parental cells. Furthermore, immunohistochemical analysis of MJD transgenic mice and post-mortem human brain tissues showed increased expression of Hsp27 compared to normal control brain, suggesting an up-regulation of Hsp27 in the end stage of MJD. However, mutant cells of earlier passages were more susceptible to serum deprivation than mutant cells of later passages, indicating weak tolerance toward stress in cells with reduced Hsp27. While heat shock was used to assess the stress response, cells expressing mutant ataxin-3 displayed normal response upon heat shock stimuli when compared to the parental cells. Taken together, we proposed that during the early disease stage, the reduction of Hsp27 synthesis mitigated the ability of neuron cells to cope with cytotoxicity induced by mutant ataxin-3, triggering the cell death process during the disease progress. In the late stage of disease, after prolonged stressful conditions of polyglutamine cytotoxicity, the increased level of Hsp27 may reflect a dynamic process of the survived cells to unfold and remove mutant ataxin-3. However, this increased Hsp27 still cannot reverse the global dysfunction of cellular proteins due to accumulation of cytotoxic effects.