The Arabidopsis thaliana-Fusarium oxysporum strain 5176 pathosystem: an overview.

Fusarium oxysporum is a soil-borne fungal pathogen of several major food crops. Research on understanding the molecular details of fungal infection and the plant's defense mechanisms against this pathogen has long focused mainly on the tomato-infecting F. oxysporum strains and their specific host plant. However, in recent years, the Arabidopsis thaliana-Fusarium oxysporum strain 5176 (Fo5176) pathosystem has additionally been established to study this plant-pathogen interaction with all the molecular biology, genetic, and genomic tools available for the A. thaliana model system. Work on this system has since produced several new insights, especially with regards to the role of phytohormones involved in the plant's defense response, and the receptor proteins and peptide ligands involved in pathogen detection. Furthermore, work with the pathogenic strain Fo5176 and the related endophytic strain Fo47 has demonstrated the suitability of this system for comparative studies of the plant's specific responses to general microbe- or pathogen-associated molecular patterns. In this review, we highlight the advantages of this specific pathosystem, summarize the advances made in studying the molecular details of this plant-fungus interaction, and point out open questions that remain to be answered.

3D Printing of Collagen/Oligomeric Proanthocyanidin/Oxidized Hyaluronic Acid Composite Scaffolds for Articular Cartilage Repair.

Articular cartilage defects affect millions of people worldwide, including children, adolescents, and adults. Progressive wear and tear of articular cartilage can lead to progressive tissue loss, further exposing the bony ends and leaving them unprotected, which may ultimately cause osteoarthritis (degenerative joint disease). Unlike other self-repairing tissues, cartilage has a low regenerative capacity; once injured, the cartilage is much more difficult to heal. Consequently, developing methods to repair this defect remains a challenge in clinical practice. In recent years, tissue engineering applications have employed the use of three-dimensional (3D) porous scaffolds for growing cells to regenerate damaged cartilage. However, these scaffolds are mainly chemically synthesized polymers or are crosslinked using organic solvents. Utilizing 3D printing technologies to prepare biodegradable natural composite scaffolds could replace chemically synthesized polymers with more natural polymers or low-toxicity crosslinkers. In this study, collagen/oligomeric proanthocyanidin/oxidized hyaluronic acid composite scaffolds showing high biocompatibility and excellent mechanical properties were prepared. The compressive strengths of the scaffolds were between 0.25-0.55 MPa. Cell viability of the 3D scaffolds reached up to 90%, which indicates that they are favorable surfaces for the deposition of apatite. An in vivo test was performed using the Sprague Dawley (SD) rat skull model. Histological images revealed signs of angiogenesis and new bone formation. Therefore, 3D collagen-based scaffolds can be used as potential candidates for articular cartilage repair.

Heterogeneous Nuclear Ribonucleoprotein H1 Coordinates with Phytochrome and the U1 snRNP Complex to Regulate Alternative Splicing in Physcomitrella patens.

Plant photoreceptors tightly regulate gene expression to control photomorphogenic responses. Although gene expression is modulated by photoreceptors at various levels, the regulatory mechanism at the pre-mRNA splicing step remains unclear. Alternative splicing, a widespread mechanism in eukaryotes that generates two or more mRNAs from the same pre-mRNA, is largely controlled by splicing regulators, which recruit spliceosomal components to initiate pre-mRNA splicing. The red/far-red light photoreceptor phytochrome participates in light-mediated splicing regulation, but the detailed mechanism remains unclear. Here, using protein-protein interaction analysis, we demonstrate that in the moss Physcomitrella patens, phytochrome4 physically interacts with the splicing regulator heterogeneous nuclear ribonucleoprotein H1 (PphnRNP-H1) in the nucleus, a process dependent on red light. We show that PphnRNP-H1 is involved in red light-mediated phototropic responses in P. patens and that it binds with higher affinity to the splicing factor pre-mRNA-processing factor39-1 (PpPRP39-1) in the presence of red light-activated phytochromes. Furthermore, PpPRP39-1 associates with the core component of U1 small nuclear RNP in P. patens Genome-wide analyses demonstrated the involvement of both PphnRNP-H1 and PpPRP39-1 in light-mediated splicing regulation. Our results suggest that phytochromes target the early step of spliceosome assembly via a cascade of protein-protein interactions to control pre-mRNA splicing and photomorphogenic responses.

Cellulose synthesis during cell plate assembly.

The plant cell wall surrounds and protects the cells. To divide, plant cells must synthesize a new cell wall to separate the two daughter cells. The cell plate is a transient polysaccharide-based compartment that grows between daughter cells and gives rise to the new cell wall. Cellulose constitutes a key component of the cell wall, and mutants with defects in cellulose synthesis commonly share phenotypes with cytokinesis-defective mutants. However, despite the importance of cellulose in the cell plate and the daughter cell wall, many open questions remain regarding the timing and regulation of cellulose synthesis during cell division. These questions represent a critical gap in our knowledge of cell plate assembly, cell division and growth. Here, we review what is known about cellulose synthesis at the cell plate and in the newly formed cross-wall and pose key questions about the molecular mechanisms that govern these processes. We further provide an outlook discussing outstanding questions and possible future directions for this field of research.

Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets.

New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.

Light-mediated modulation of helix angle and rate of seminal root tip movement determines root morphology of young rice seedlings.

Seminal root growth is one of the factors to determine rice seedling establishment. Our previous reports showed light can induce Z-type wavy root and coiling root morphology in several rice (Oryza sativa L.) varieties, and the regulated Z-type and unregulated coil seminal roots were resulted by different circumnutational trajectories. Moreover, the light-induced seminal root waving was conducted by an NO-dependent signaling pathway. In order to further reveal the difference of root tip movement between straight and wavy seminal roots; here, the root tip movement trajectories of Tainung 67 variety (TNG67; presented straight root in light conditions) and Taichung Native 1 (TCN1; presented Z-type wavy root in light) were recorded and analyzed in both white light and dark (dim far-red light was applied in dark for taking time-lapse photography) conditions. The results showed the root tip movement of both rice varieties in low intensity of dim far-red light conditions were followed the circumnutation path. However, the stimuli of high intensity of white light would increase the root helix angle in TCN1 seedlings but not in TNG67. In addition, slowing down the rate of root helix was induced by white light treatment in TCN1 but not in TNG67 seedlings. In conclusion, changes of TCN1 rice seminal root morphology from straight to wavy type stimulated by light was resulted by both helix angle increasing and circumnutation rate slowing of root tip movement.

Light-modulated seminal wavy roots in rice mediated by nitric oxide-dependent signaling.

Rice (Oryza sativa L.) seminal roots from germinated seeds help establish seedlings, but the seminal root growth and morphology are sensitive to environmental factors. Our previous research showed that several indica-type rice varieties such as Taichung native 1 (TCN1) showed light-induced wavy roots. Also, auxin and oxylipins are two signaling factors regulating the wavy root photomorphology. To investigate the signaling pathway, here, we found that nitric oxide (NO) was a second messenger triggering the signal transduction of light stimuli to induce the wavy morphology of seminal roots in rice. Moreover, interactions between oxylipins and phytohormones such as ethylene and auxin participating in the NO-dependent regulatory pathway of light-induced wavy roots were examined. The order of action of signaling components in the pathway was NO, oxylipins, ethylene, and auxin.

Functional Genomics Reveals Linkers Critical for Influenza Virus Polymerase.

UNLABELLED: Influenza virus mRNA synthesis by the RNA-dependent RNA polymerase involves binding and cleavage of capped cellular mRNA by the PB2 and PA subunits, respectively, and extension of viral mRNA by PB1. However, the mechanism for such a dynamic process is unclear. Using high-throughput mutagenesis and sequencing analysis, we have not only generated a comprehensive functional map for the microdomains of individual subunits but also have revealed the PA linker to be critical for polymerase activity. This PA linker binds to PB1 and also forms ionic interactions with the PA C-terminal channel. Nearly all mutants with five-amino-acid insertions in the linker were nonviable. Our model further suggests that the PA linker plays an important role in the conformational changes that occur between stages that favor capped mRNA binding and cleavage and those associated with viral mRNA synthesis. IMPORTANCE: The RNA-dependent RNA polymerase of influenza virus consists of the PB1, PB2, and PA subunits. By combining genome-wide mutagenesis analysis with the recently discovered crystal structure of the influenza polymerase heterotrimer, we generated a comprehensive functional map of the entire influenza polymerase complex. We identified the microdomains of individual subunits, including the catalytic domains, the interaction interfaces between subunits, and nine linkers interconnecting different domains. Interestingly, we found that mutants with five-amino-acid insertions in individual linkers were nonviable, suggesting the critical roles these linkers play in coordinating spatial relationships between the subunits. We further identified an extended PA linker that binds to PB1 and also forms ionic interactions with the PA C-terminal channel.

Pre-existent Hsp72 contributes to glutamine-induced hepatic hsp72 gene activation during heat shock recovery period in rat.

SCOPE: Functional maintenance of liver is very important at all times for personal health. Hsp induction is associated with the protection of the organ. Glutamine, a nutrient inducer of Hsps, enhances cellular survival via Hsp72 induction in several organs, but not in the liver. The present study showed a novel approach to facilitate glutamine-induced hepatic Hsp72 synthesis and its possible mechanisms were discussed. METHODS AND RESULTS: Sprague-Dawley rats were used as the experimental animals and the livers were the targets. Glutamine was administered via tail-vein injection, and its effects on hsp72 gene activation, including Hsp72 expression, heat shock factor-1 (HSF-1) phosphorylation and DNA-binding activation, were evaluated. The results showed that Hsp72 itself played a critical role in glutamine-induced hepatic Hsp72 synthesis during HS recovery period in a dose-dependent manner of preexistent Hsp72. The peak value of HSF-1 phosphorylation, HSF-1 DNA-binding activity, hsp72 mRNA accumulation, and Hsp72 synthesis was detected at 8 h after glutamine administration. CONCLUSION: Glutamine switched on alteration pathway in inducing hsp72 gene activation. The existence of Hsp72 plays a critical role in the reactivation of hsp72 gene. Glutamine sustained the induction of intracellular Hsp72, which could be beneficial in protecting the liver from various injuries.

Effect of the interaction between light and touch stimuli on inducing curling seminal roots in rice seedlings.

Root development is sensitive to environmental stimuli. We have recently reported that the light signal could promote the helical growth of seminal roots and drive the wavy root morphology in rice (Oryza sativa L.) young seedlings. The light-stimulated wavy roots were mostly performed in indica-type rice varieties (e.g. Taichung Native 1; TCN1) but not in japonica rice (e.g. Tainung 67; TNG67). Here, we demonstrated that the light-driven circumutation trajectory of TCN1 seminal roots could be changed if the seedling roots were grown in the medium containing high concentration of Phytagel. The data showed the root morphology would be modulated from wavy to curling when the Phytagel concentration was increased to 2%. However, the touch-stimulated curling root phenotype could not be performed in dark. In addition, the touch-induced curling roots were not appeared in the TNG67 rice cultivar. Although touch stimuli could not induce wavy/curling root phenotype in dark, it could modify the light-promoted helical growth to conduct curling roots in TCN1 rice seedlings. Thus, it was suggested that there is a crosstalk mechanism between touching-induced root curling and light-stimulated root waving.

Rice develop wavy seminal roots in response to light stimulus.

Rice (Oryza sativa L.) seminal roots are the primary roots to emerge from germinated seeds. Here, we demonstrate that the photomorphology of the seminal roots was diverse among rice varieties, and the light-induced wavy roots were found mostly in indica-type rice varieties. The light-induced wavy morphology in rice seminal roots has been different with curling or coiling roots in some other specific conditions, such as high air humidity or high nitrogen nutrient. The efficiency of light-induced root waving was developmental stage dependent. The wavy root phenotype was caused by asymmetric cell growth around the stele. Using the inhibitors to block auxin polar transport and fatty acid oxygenation, the role of auxin and oxylipins in the morphogenesis of light-induced wavy roots was investigated. Expressions of genes encoded in the enzymes involved in fatty acid oxygenation in light-exposed roots were monitored by reverse transcriptase-polymerase chain reaction. Our results suggested that auxin polar transport was essential for inducing wavy seminal roots by light stimulus. In addition, the ketol oxylipins derived from allene oxide synthase (EC 4.2.1.92)-mediated fatty acid oxygenation function as intracellular signals for triggering the light-induced wavy root phenotype.

N-acetylcysteine prevents mitochondria from oxidative injury induced by conventional peritoneal dialysate in human peritoneal mesothelial cells.

INTRODUCTION: Bioincompatible peritoneal dialysate fluids (PDFs) may lead to peritoneal injury. The present study investigated the possible effects of N-acetylcysteine (NAC) during conventional PDF exposure for human peritoneal mesothelial cells (HPMCs). METHODS: Cultured HPMCs were incubated with conventional 1.5% dextrose PDF for different time periods, and NAC was utilized as the antioxidant. The cell survival, superoxide accumulation, mitochondrial membrane potential (Deltapsim), expression of heat shock protein 72(HSP72), catalase, superoxide dismutase (SOD), and glutathione content of HPMCs were evaluated. RESULTS: HPMC exposed to PDF resulted in a significant decrease in cell survival in a time-dependent manner, which was reversed by NAC. PDF exposure resulted in intracellular accumulation of superoxide in a time-dependent manner, with collapse of Deltapsim as well. The activity of enzymatic antioxidant, SOD and catalase remained the same in all groups. However, the reduced glutathione was significantly suppressed after PDF exposure. NAC treatment preserved the content of intracellular reduced glutathione, and also attenuated the PDF-induced superoxide accumulation and Deltapsim collapse. Moreover, the enhanced expression of HSP72 induced by PDF exposure was also reversed by NAC. CONCLUSION: Depletion of a nonenzymatic antioxidant, i.e. reduced glutathione, in HPMC is a crucial cause of PDF-induced oxidative stress. NAC protects HPMCs from PDF-induced cellular damage by preserving the reduced glutathione.

Heat shock response protects human peritoneal mesothelial cells from dialysate-induced oxidative stress and mitochondrial injury.

BACKGROUND: Chronic peritoneal dialysis (PD) is one of the major therapies for uremic patients. However, the peritoneal mesothelial cells (PMCs) are subject to the injury by bioincompatible dialysates. The aim of this study is to investigate the protective roles and mechanisms of heat shock response in PMCs. METHODS: Primary cultured human PMCs (HPMCs) were subjected to commercial peritoneal dialysates. The cell viability was assayed by MTT test and Annexin V assay. The expression of HSPs was detected by Western blots analysis. Intracellular hydrogen peroxide and superoxide anion were detected using H(2)DCFDA and dHE probe, respectively, with flow cytometry. The mitochondrial membrane potential (DeltaPsim) of HPMCs was evaluated using JC1 probe with flow-cytometry. RESULTS: Exposure of HPMCs to 1.5%, 2.5%, and 4.25% dextrose, and 7.5% icodextrin dialysates, respectively, for 60 min resulted in significantly accumulation of intracellular reactive oxygen species (ROS), DeltaPsim loss, and cell death in HPMCs. Amino acid dialysates exhibited no significant cytotoxicity. Adjusting the acidity in 1.5% dextrose and icodextrin dialysate significantly attenuated the dialysate-induced ROS generation and cell death in HPMCs. Heat pretreatment (41 degrees C, 30 minutes), which induced HSP 27 and 72 syntheses, significantly attenuated the dialysate-induced intracellular ROS accumulation, Dym loss, and cell death in HPMCs. CONCLUSIONS: In conclusion, the acidic bioincompatible dialysates induce oxidative stress, DeltaPsim loss, and subsequent cell death in HPMCs. Amino acid dialysates is more biocompatible than glucose and icodextrin dialysates to HPMCs. Heat shock response protects HPMCs from the bioincompatible dialysates-induced cellular damage.

Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia.

Disseminated intravascular coagulation (DIC) is a lethal situation in severe infections, characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. Current clinical trials are not promising. In this study, we investigated the protective effect of curcumin in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by sustained infusion of LPS (10 mg/kg body weight) for 4 h through the tail vein. Curcumin (60 mg/kg body weight) was given intraperitoneally 3 h before LPS infusion. Results showed that, in vivo, curcumin reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-alpha levels and the consumption of peripheral platelets and plasma fibrinogen. Furthermore, in vivo curcumin also has the effect of preventing the formation of fibrin deposition in the glomeruli of kidney. These results reveal the therapeutic potential of curcumin in infection-related coagulopathy of DIC.

Previous heat shock facilitates the glutamine-induced expression of heat-shock protein 72 in septic liver.

OBJECTIVES: This study investigated the effects of glutamine administration on the expression of the heat-shock protein 72 (Hsp72) in the liver during sepsis. The role of heat-shock factor 1 (HSF-1) was analyzed for possible mechanisms to the phenomenon. METHODS: Male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Heat-shock treatment was applied to the rats' whole body using an electric heating pad 24 h before CLP. Glutamine or saline was administered 1 h after initiation of sepsis by tail vein injection. The Hsp72 and HSF-1 expressions were detected using western blot analysis, and Hsp72 mRNA expression was measured using reverse transcription-polymerase chain reaction. RESULTS: The Hsp72 content noticeably increased in the livers of preheated rats supplied by glutamine 1 h after sepsis. However, no further synthesis of Hsp72 was found in septic livers or sham glutamine-treated livers. Hsp72, which was induced by preheating, decreased with time, whereas a large amount of Hsp72 could be detected by glutamine administration. Reverse transcription-polymerase chain reaction data indicated that Hsp72 mRNA could be detected only in the group treated with preheating and glutamine administration. The translocation of HSF-1 occurred significantly during sepsis in preheated and non-preheated rats. However, only the preheated group showed the phosphorylation in HSF-1. With the administration of glutamine, the nuclear accumulation of phosphorylated HSF-1 was observed to decline significantly 9 and 18 h after CLP when the Hsp72 mRNA became detectable. CONCLUSIONS: These results demonstrated that Hsp72 could be induced by glutamine in septic liver only if the liver was preconditioned by heat-shock response. The selective facilitating effect might depend on the accumulation of intranuclear phosphorylated HSF-1 caused by previous heat-shock treatment.

Proteomic alteration of mitochondrial aldehyde dehydrogenase 2 in sepsis regulated by heat shock response.

The present study was designed to investigate the proteomic alteration of hepatic mitochondria during sepsis and to explore the possible effects induced by heat shock treatment. Sepsis was induced by cecal ligation and puncture in Sprague-Dawley rats. Liver mitochondrial proteins were isolated and evaluated by 2-dimensional electrophoresis with broad pH-ranged (pH 3 - 10) immobile DryStrip and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein spots were visualized with silver stain and analyzed by Bio-2D software. Results showed that around 120 dominant spots could be separated and visualized distinctly by 2-dimensional electrophoresis analysis. Among them, three spots with the same molecular weight (56.4 kd), mitochondrial protein 1 (MP1), MP2, and MP3, were significantly altered in septic specimens. When analyzed by liquid chromatography-tandem mass spectrometry, the three spots all revealed to be an identical enzyme: aldehyde dehydrogenase 2 (ALDH2, EC 1.2.1.3). During sepsis, MP1 and MP2 were downregulated, whereas MP3 was upregulated concomitantly. Interestingly, heat shock treatment could reverse this phenomenon. Phosphoprotein staining showed that the degree of phosphorylation is higher in MP1 and MP2 than that in MP3. The enzyme activity assay showed that ALDH2 activity was downregulated in nonheated septic rats of 18 h after cecal ligation and puncture operation, and preserved in heated septic rats. The results of this study suggest that posttranslation modification, highly possible the phosphorylation, in ALDH2 may play a functional role in the pathogenesis of sepsis and provide a novel protective mechanism of heat shock treatment.

Previous heat shock treatment attenuates lipopolysaccharide-induced hyporesponsiveness of platelets in rats.

Several studies demonstrated that previous heat shock treatment caused expression of heat shock proteins (HSPs) and reduced organ dysfunction and mortality in experimentally induced severe sepsis. However, the protective mechanism on platelet function remains unclear. The aim of this study was to investigate the effect of heat shock treatment on platelet aggregation ex vivo in endotoxin-induced rats with sepsis. Rats of the heated group were heated by whole-body hyperthermia 18 h before lipopolysaccharide (LPS) injection. Blood samples were obtained from the carotid artery 90 min after LPS injection. Platelet aggregation ability was measured by aggregometer. Results revealed that platelet aggregation ex vivo was significantly inhibited in LPS-induced rats in a manner of dose dependence. Previous heat shock treatment caused overexpression of HSPs and significantly attenuated the LPS-induced platelet hyporesponsiveness. This attenuation disappeared in accordance with absence of HSP72 at 7 days after heat shock treatment. Aggregation of normal platelets was also inhibited by incubating with plasma obtained from endotoxemic rats but not from preheated endotoxemic rats. Furthermore, no significant hyporesponsiveness was found in endotoxemic platelets in addition to preheated endotoxemic plasma. The addition of H2O2 scavenger catalase diminished the platelet hyporesponsiveness significantly only in nonheated endotoxemic rats. Moreover, the plasma nitrite and nitrate levels were significantly attenuated in preheated endotoxemic rats. These results revealed that previous heat shock treatment might attenuate LPS-induced hyporesponsiveness of platelets by changing the plasma components possibly through altering H2O2 and nitric oxide concentrations.

In vivo heat shock protein assembles with septic liver NF-kappaB/I-kappaB complex regulating NF-kappaB activity.

This study elucidates the mechanism through which heat shock treatment influences the outcome of sepsis. Post-heat shock sepsis was induced in rats by CLP 24 h after whole-body hyperthermia. Liver cytosolic and nuclear fractions were collected and analyzed in early and late sepsis rats (sacrificed 9 and 18 h after CLP, respectively). During sepsis, levels of I-kappaB and nuclear factor-kappaB (NF-kappaB) declined in the cytosol of liver, whereas NF-kappaB increased in nucleus. NF-kappaB activity was significantly enhanced during sepsis, and the products of NF-kappaB target genes, such as TNF-alpha and inducible nitric oxide synthase (iNOS), were overexpressed. Heat shock treatment, inducing heat shock protein synthesis, prevented down-regulation of cytosolic I-kappaB and decreased translocation of NF-kappaB into the nucleus. Therefore, the sepsis-induced acceleration of NF-kappaB activation was inhibited. Expression of TNF-alpha and iNOS mRNA was also down-regulated. Coimmunoprecipitation with anti-NF-kappaB (p65) and anti-IkappaB antibodies verified an assembling phenomenon of heat shock protein (HSP) 72 with NF-kappaB and I-kappaB. We suggest that the mechanism preventing septic activation of NF-kappaB is that oversynthesized HSP72 forms a complex with NF-kappaB/I-kappaB, thus inhibiting nuclear translocation of NF-kappaB. HSP72 appears to play a crucial protective role in modulating the gene expression controlled by NF-kappaB in sepsis.

Expression of Hsp72 in lymphocytes in patients with febrile convulsion.

The pathophysiology of febrile convulsion, the most common childhood neurologic disease, remains unclear. In this study, we investigated what role a heat shock protein plays in this disease. We enrolled eight boys and two girls with febrile convulsion and 10 age-matched healthy controls. We did a biosynthetic evaluation of both groups by separating lymphocytes and measuring the expression of heat shock protein 72 before and after heat shock treatment. Before the treatment, both groups were found to have small amounts of constitutive heat shock protein 72. Afterwards, its expression increased in both groups, and no statistical difference was found between the increases in the two groups. In addition, there was no obvious difference in the susceptibility to produce heat shock proteins. However, the febrile convulsion group was found to have a significant decrease in phosphorylation of heat shock protein 72. These results suggest the possible involvement of post-translational modification of heat shock proteins, most likely phosphorylation, in the pathogenesis of febrile convulsion.

Cytochrome c oxidase as the target of the heat shock protective effect in septic liver.

Liver function failure is one of the characteristics of critically ill, septic patients and is associated with worse outcome. Our previous studies have demonstrated that heat-shock response protects cells and tissue from subsequent insults and improves survival during sepsis. In this study, we have shown that mitochondrial cytochrome c oxidase (CCO) is one of the major sources of that protective effect. Experimental sepsis was induced by the cecal ligation and puncture (CLP) method. Heat-shock treatment was induced in rats by hyperthermia 24 h before CLP operation. The results showed that ATP content of the liver declined significantly, and the enzymatic activity of mitochondrial CCO was apparently suppressed during the late stages of sepsis. The mitochondrial ultrastructure of septic liver showed the deformity, mild swelling and inner membrane budding. Heat-shock treatment led to heat-shock protein 72 overexpression and prevented the downregulation of Grp75 during sepsis. On the contrary, the expression of the enzyme complex and its activity were preserved, associated with the minimization of ultrastructural deformities. In conclusion, the maintenance of mitochondrial function, especially the CCO, may be an important strategy in therapeutic interventions of a septic liver.