OBJECTIVEThis study was to develop a new method that can improve flap survival.

METHODSA long skin flap spanning the full length of the rat dorsum was used to make a bilateral skin tube, which was based on the lateral thoracic artery proximally, and the deep circumflex iliac artery distally. The animals were randomly divided into 3 groups of 8 rats in each group: the control and two experimental groups with elevation of the tube (the proximal pedicle divided) immediately or 24 hours following ischemic preconditioning. All tube flaps were observed for 3 days postoperatively and the surviving flap area was measured as a percentage of the whole flap using the paper template technique. Heat shock protein 70 in the three groups was examined by means of immunohistochemistry.

RESULTSThere was an overall statistical significance in comparison of flap survival of the preconditioned flaps with that of the controls. There was no statistical significance between the two preconditioned groups. Heat shock protein 70 (HSP70) was demonstrated immunohistochemically in the preconditioned skin flap but not in the control skin flap.

CONCLUSIONIschemic preconditioning can improve skin flap survival and the contents of HSP70. It is suggest that the mechanism be related to the function of HSP70.

Animals ; HSP70 Heat-Shock Proteins ; analysis ; physiology ; Immunohistochemistry ; Ischemic Preconditioning ; Male ; Rats ; Rats, Wistar ; Surgical Flaps

BACKGROUNDGlucocorticoid (GC) insensitivity/GC resistance is an important etiological and prognostic factor in multiple diseases and pathophysiological processes such as scald, shock and asthma. The function of GC was mediated by glucocorticoid receptor (GR). Scald not only decreased the expression of GR but also reduced the affinity of GR, which played an important role in GC resistance in scalded rats. Whereas the molecular mechanism responsible for the decrease of GR affinity resulted from scald remains unclear. Recent studies showed that the changes of heat shock proteins (hsp) especially hsp90 and hsp70 of GR heterocomplex were associated with GR low affinity in vitro.

METHODSThe affinity of GR in hepatic cytosols and in the cytosols of SMMC-7721 cells were determined by radioligand binding assay and scatchard plot. GR heterocomplex in cytosols were captured by coimmunoprecipation and the levels of hsp90 and hsp70 of GR complex were detected by quantitative Western blotting.

RESULTSSimilar with that of hepatic cytosol of scalded rats, a remarkable decrease of GR affinity was also found in the cytosol of heat stressed SMMC-7721 cells. The level of hsp70 of GR complex in hepatic cytosol of scalded rats (30% total body surface area immersion scald) and in cytosol of heat stressed human hepatocarcinoma cell line SMMC-7721 were both increased by 1.5 fold, whereas no change of hsp90 in GR heterocomplex was found. According to the correlation analysis, there may be a positive relationship between increased hsp70 of GR complex and decreased GR affinity in the cytosols.

CONCLUSIONSThe primary results indicated that the level of hsp70 of GR heterocomplex was increased in the hepatic cytosol of scalded rats and the cytosol of heat stressed SMMC-7721 cells. The increase of hsp70 of GR complex might be associated with the decrease of GR affinity.

Animals ; Blotting, Western ; Burns ; physiopathology ; Cell Line ; HSP70 Heat-Shock Proteins ; metabolism ; Heat-Shock Response ; physiology ; Immunoprecipitation ; Protein Binding ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; metabolism

Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

OBJECTIVETo establish an effective and stable rabbit heat acclimatization model for the experiment of heat acclimatization mechanisms.

METHODSSixteen healthy male rabbits were divided into heat acclimatization group and control group randomly (n = 8). Heat acclimatization (HA) group was kept in simulation chamber with dry bulb temperature of (36 +/- 1) degrees C, wet bulb temperature of (29 +/- 0.5) degrees C, black-bulb temperature of (40 +/- 1.0) degrees C, 100 min/day for 21 days. Control group was kept in the room with temperature of 20 degrees C and relative humidity < 60% during 20 days, then removed into simulation chamber on day 21 to estimate and monitor the rectal temperature together with the heat acclimatization group. Venous blood of control and heat acclimatization group before and after heat exposure on the 1st day, 11th day and 21st day were collected to detect levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and heat shock protein 70 (HSP70) by ELISA analysis.

RESULTS(1) Rectal temperature: There was no significant change in control group during 21 days. In heat acclimatization group, it increased (2.07 +/- 0.43) degrees C after the 1st exposure, and increased (1.78 +/- 0.37) degrees C after the 11th exposure, the range of increasing decreased (0.29 +/- 0.09) degrees C. After the 21st exposure, it increased (1.52 +/- 0.29) degrees C, which was (0.55 +/- 0.14) degrees C lower than that of the 1st (P < 0.05),and (0.53 +/- 0.14) degrees C lower to that of the control group under 1st heat stress (P < 0.05); (2) The level of TNF-alpha after the 1st exposure increased significantly (P < 0.05), but didn't raise along with the exposure times. And fell back to the original level after the 11th and 21st exposure. Compared with control group, the level of IL-6 increased after the 1st, 11th and 21st exposure (P < 0.05), and maintained highly after the 11th and 21st exposure. Compared with the control group, the level of HSP70 increased dramatically with the heat exposure times. Significant increasing of (HSP70) could be detected after the 11th and 21st exposure (P < 0.05), but there was no difference to that of the 1st exposure.

CONCLUSIONProlonged or repeated exposure to heat stressful environmental conditions can reduce the physiological strain, improve heat tolerance, elicits heat acclimatization.

Acclimatization ; physiology ; Animals ; Body Temperature Regulation ; physiology ; Disease Models, Animal ; HSP70 Heat-Shock Proteins ; metabolism ; Heat Stress Disorders ; metabolism ; physiopathology ; Hot Temperature ; Male ; Rabbits

This article is to summarize the molecular and functional analysis of the gene "suppression of tumorigenicity 13" (ST13). ST13 is in fact the gene encoding Hsp70 interacting protein (Hip), a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). By collaborating with other positive co-factors such as Hsp40 and the Hsp70-Hsp90 organizing protein (Hop), or competing with negative co-factors such as Bcl2-associated athanogen 1 (Bag1), Hip facilitates may facilitate the chaperone function of Hsc/Hsp70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and regulators of proliferation or apoptosis. Although the nomenclature of ST13 implies a role in the suppression of tumorigenicity (ST), to date available experimental data are not sufficient to support its role in cancer development, except for the possible down-regulation of ST13 in gastric and colorectal cancers. Further investigation of this gene at the physiological level would benefit our understanding of diseases such as endocrinological disorders, cancer, and neurodegeneration commonly associated with protein misfolding.
Adenosine Triphosphate ; metabolism ; Animals ; Carrier Proteins ; chemistry ; genetics ; physiology ; Cloning, Molecular ; HSP70 Heat-Shock Proteins ; metabolism ; Humans ; Protein Folding ; Tumor Suppressor Proteins ; chemistry ; genetics ; physiology

Animals ; HSP70 Heat-Shock Proteins ; metabolism ; Male ; Physical Conditioning, Animal ; Physical Endurance ; physiology ; Quadriceps Muscle ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the expression and relationship between HSP70 and caspase-3 in knee osteoarthritis.

METHODSForty adult SD rats were divided into experimental group and control group. Thirty rats in experimental group, anterior cruciate ligament transaction (ACLT) was cut off and partial meniscectomy of 1/3 inside incision were performed to reproduce knee osteoarthritis (KOA) model according to Hulth methos, and the other 10 rats was treated with nothing as control group. The rats were sent to the cage and free to move. At 1, 2 and 4 weeks later, the arthritis cartilage of femoral and tibial end were observed through immunohistochemistry staining and light microscope. Meanwhile, Mankin scale system was adopted for histomorphology evaluation.

RESULTSChanges of KOA such as hyperplastic synovium,erosion on the surface of cartilage and so on were found in experiment group, the expression of HSP70 was augmentation all the time, but the expression of caspase-3 was reduction 1 week later; no similar changes were found in control group. Mankin scale system showed that there were significant differences in the first week as compared with the second week and 4th week (both P < 0.01).

CONCLUSIONHeat shock protein inhibit the apoptosis of cartilage cells and protect the cartilage cells in knee osteoarthritis, the conservative treatment for clinical provide objective scientific basis.

Animals ; Apoptosis ; Cartilage ; pathology ; Caspase 3 ; physiology ; Chondrocytes ; pathology ; Female ; HSP70 Heat-Shock Proteins ; physiology ; Male ; Osteoarthritis, Knee ; pathology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDIn patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).

METHODSAcute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-alpha) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-kappaB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.

RESULTSTreatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-alpha concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-alpha concentrations.

CONCLUSIONSThe results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome (SIRS)-like response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

Acute Disease ; Animals ; Ceruletide ; toxicity ; Female ; HSP70 Heat-Shock Proteins ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis ; etiology ; Systemic Inflammatory Response Syndrome ; etiology ; Toll-Like Receptor 4 ; physiology

The 'fetal origin' hypothesis propose the alteration in fetal environment result in developmental adaptation, the permanently change in structure, physiology and metabolism, thereby predisposing to cardiovascular, metabolic and endocrine disease in adult life. Evidence is accumulating that the fetal environment affects newborn cardiac structure and function in humans, and blood pressure (BP) in newborn predicts the likelihood of developing hypertension in adult life. However, few studies have reported the influence of fetal factors on BP in neonates and an attempt to relate fetal factors to a neonate's BP seems to be important to identify individuals at risk of developing hypertension later in life. As the placenta is the regulator of nutrient composition and supply from mother to fetus and the source of hormonal signals that affect maternal and fetal metabolism, appropriate development of the placenta is crucial to normal fetal development. By virtue of these roles the placenta is in a key position to play a direct role in fetal programming. The aim of this study was to evaluate positive relationship between placental oxidative stress and BP in their healthy newborn offsprings, and propose to relate fetal factors to a neonatal BP. Systemic blood pressure was measured by automated device in 68 healthy term newborns who were born at Ewha Womans Medical Center, and their tissue samples of placentas were obtained from 40 cases which are 20 cases from high neonatal blood pressure group and 20 cases from low neonatal blood pressure group. We investigated placental expressions for heat shock protein (HSP) 70 and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), as markers for placental oxidative stress using immunohistochemistry and Western blot analysis, and evaluated their association with BP in healthy term newborn babies. The mean values of placental LOX-1 and HSP 70 were significantly higher in newborns with high BP group compared to those with low BP group. Increase in placental oxidative stress was associated with higher newborn systolic blood pressure. These findings suggest that newborn blood pressure may represent prenatal influence on cardiac structure and function.
Adult ; Blood Pressure* ; Blotting, Western ; Endocrine System Diseases ; Female ; Fetal Development ; Fetus ; Heat-Shock Proteins* ; Hot Temperature* ; HSP70 Heat-Shock Proteins* ; Humans ; Hypertension ; Immunohistochemistry ; Infant, Newborn* ; Lipoproteins* ; Metabolism ; Mothers ; Oxidative Stress ; Physiology ; Placenta ; Virtues

To examine the significance of heat shock protein 70 mRNA in ototoxicity resulted from gentamicin (GM), twenty healthy albino guinea pigs (200-250 g) of either sex with a positive Prier reflex were divided into two groups randomly. In GM group the animals received 100 mg/kg GM daily by intraperitoneal injection for 10 d. In saline control group the animals received 2.5 ml/kg saline daily by intraperitoneal injection for 10 d. Auditory brainstem response (ABR) thresholds were recorded in each animal before and 1 d after GM or saline administration. After the second ABR measurement, the expression of HSP70 mRNA in guinea pig cochlea was observed with in situ hybridization and image quantitative analysis system. The results showed that the threshold of ABR in the GM group was significantly higher than that of the saline control (P< 0.001). The expression of HSP70 mRNA was more intensive in stria vascularis, spiral ligament and spiral ganglion cells in the GM group than that of the saline control group. These results suggest that administration of gentamicin can induce the expression of HSP 70 mRNA in guinea pig cochlea, and that this effect may protect hearing function from ototoxicity.
Animals ; Cochlea ; metabolism ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Gentamicins ; toxicity ; Guinea Pigs ; HSP70 Heat-Shock Proteins ; biosynthesis ; genetics ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation