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Biomedical subjects

Z B Yu

Publications and source records attributed to Z B Yu.

At least 19 recordsLinked to original sources
PubMed2001

The highly conserved COOH terminus of troponin I forms a Ca2+-modulated allosteric domain in the troponin complex.

The primary structure of the COOH-terminal region of troponin I (TnI) is highly conserved among the cardiac, slow, and fast skeletal muscle TnI isoforms and across species. Although no binding site for the other thin filament proteins is found at the COOH terminus of TnI, truncations of the last 19-23 amino acid residues reduce the activity of TnI in the inhibition of actomyosin ATPase and result in cardiac muscle malfunction. We have developed a specific monoclonal antibody (mAb), TnI-1, against the conserved COOH terminus of TnI. Using this mAb, isolation of the troponin complex by immunoaffinity chromatography from muscle homogenate and immunofluorescence microscopic staining of myofibrils indicate that the COOH terminus of TnI forms an exposed structure in the muscle thin filament. Binding of this mAb to the COOH terminus of cardiac TnI induced extensive conformational changes in the protein, suggesting an allosteric role of this region in the functional integrity of troponin. In the absence of Ca2+, the binding of troponin C and troponin T to TnI had very little effect on the conformation of the COOH terminus of TnI as indicated by the unaffected mAb affinity for the TnI-1 epitope. However, Ca2+ significantly increased the accessibility of the TnI-1 epitope on TnI in the presence of troponin C and troponin T. The results provide evidence that the COOH terminus is an essential structure in TnI and participates in the allosteric switch during Ca2+ activation of contraction.

Allosteric Site↗
PubMed2001

A proteolytic NH2-terminal truncation of cardiac troponin I that is up-regulated in simulated microgravity.

In a tail suspension rat model, we investigated changes in myofilament protein during cardiac adaptation in simulated microgravity. Contractile force and velocity of cardiac muscle were decreased in the tail suspension rats as compared with the control. Ca(2+)-dependent actomyosin ATPase activity was also decreased; however, sensitivity of cardiac muscle to Ca(2+) activation was unchanged. There was no change in expression of myosin heavy chain, tropomyosin, troponin T, or troponin I isoforms in hearts of tail suspension rats. A novel finding is a fragment of cardiac troponin I (cTnI) that had increased amounts in the heart of tail suspension rats. Binding of this cTnI fragment by a monoclonal antibody that specifically recognizes the COOH terminus indicates an intact COOH terminus. NH(2)-terminal sequence analysis of the cTnI fragment revealed truncations primarily of amino acids 1-26 and 1-27 and smaller amounts of 1-30, including Ser(23) and Ser(24), which are substrates of protein kinase A phosphorylation. This cTnI fragment is present in normal cardiac muscle and incorporated into myofibrils, indicating a role in regulating contractility. This proteolytic modification of cTnI up-regulated during simulated microgravity suggests a potential role of the NH(2)-terminal segment of cTnI in functional adaptations of cardiac muscle.

Actins↗
PubMed2001

Peripheral effector mechanism hypothesis of postflight cardiovascular dysfunction.

Studies on the mechanisms of cardiovascular dysfunction after space-flight are important to illustrate the cardiovascular effect of microgravity and develop appropriate multi-system countermeasures for future long-duration spaceflights. Over the past 10 yr, we have systematically studied the adaptational changes in structure and function of both the heart and vessels, using the tail-suspension rat model to simulate microgravity effects. Our results indicate that simulated microgravity induced atrophic changes and reduced contractility of the heart muscle, and upward- and downward-regulation in structure, function, and innervation state of vessels in the brain and hind body of the rat. In addition, more recent advances in relevant ground-based and space-flight studies from different laboratories have also been reviewed. Based on these studies, it has been speculated that, in addition to hypovolemia, the microgravity-induced adaptational changes in the structure and function of the two main effectors of the cardiovascular system, i.e., the arterial smooth muscle and the cardiac muscle, might be among the most important mechanisms responsible for postflight cardiovascular dysfunction and orthostatic intolerance. In this paper we will review the available evidence with comments.

Adaptation, Physiological↗
PubMed2001

[Heat stress-induced HSP70 expression in heart and vessels of simulated weightless rats].

To examine the effect of simulated weightlessness on inducible HSP70 expression in the heart and vessel tissues of rats, a tail-suspension rat model was used to simulate weightlessness. HSP72 mRNA and HSP70 expression in heart and vessel tissues of both simulated weightless and control rats exposed to heat stress (ambient temperature, Ta = 43 degrees C) and recovered at Ta of 25 degrees C for 1 h (CON-H1, SUS-H1) or 2 h (CON-H2, SUS-H2) were analyzed using Northern blot and Western blot. The expression of HSP72 mRNA in the myocardium significantly decreased in SUS-H2, as compared with that of CON-H2 rats. The amount of HSP72 in the myocardium tended to decrease in both SUS-H1 and SUS-H2 groups, as compared with the corresponding control groups, but the differences were not statistically significant. The levels of inducible HSP70 expression in the vessels were related with their anatomical locations, for that the expression of both HSP72 mRNA and HSP72 significantly increased in basilar arteries, whereas it showed a slight decline in femoral arteries. The blunted HSP70 expression in myocardium suggests that simulated weightlessness may induce myocardial changes similar to those in aging. However, the HSP70 expression changes in arteries are in accord with the trend of differential adaptation changes in vessels to simulated weightlessness.

Animals↗
PubMed2001

[Daily 1 h standing can prevent depression of myocardial contractility in simulated weightless rats].

Objective. To observe and compare the effect of daily standing of rats for different durations in alleviating the depression of myocardial contractility induced by simulated weightlessness. Method. Fifty male Sprague-Dawley rats were randomly assigned to five groups: simultaneous control (CON), four-week tail-suspension (SUS), SUS plus daily 1 h standing (STD1), SUS plus daily 2 h standing (STD2) and SUS plus daily 4 h standing (STD4). Four weeks later, wet weights of the left soleus, testis and adrenal gland were measured, and the isometric contractile tension and its time parameters of isolated perfused papillary muscles from rats of various groups were examined. Result. Compared with CON, the wet weights of testis in different treatment groups decreased significantly (P<0.05). The wet weight of soleus in SUS decreased by 58.9% (P<0.01); but in STD1, STD2 and STD4, decreased by 38.5%, 24.0% and 11.0% (P<0.01, or P<0.05) respectively. The relative protections were 34.7%, 59.2% and 81.4% (P<0.01) respectively. In SUS group, developed tension (DT), peak rate of tension rise (+dT/dtmax) and peak rate of tension fall (-dT/dtmax) decreased by 32.2%, 29.2% and 30.7% (P<0.05), and time to peak rate of tension rise (TPP) and time to peak tension (TPT) prolonged by 21.2% and 11.0% (P<0.05), respectively. Whereas in STD1, STD2 and STD4, all the parameters reflecting myocardial contractility (like DT, + dT/dtmax, -dT/dtmax and TPP), did not show any significant change as compared with those of CON. However, being an exception, TPT still showed obvious prolongation (P<0.05) in STD1. Conclusion. Daily 1 h standing could prevent depression of myocardial contractility in rat induced by medium-term simulated weightlessness. However, with respect to prevention of atrophic changes in soleus muscle and testis, daily standing for 1 h, 2 h, or 4 h was only partially effective and even totally devoid of any effect, respectively.

Animals↗
PubMed2001

[Transition of soleus troponin I isoforms and atrophy of testis in tail-suspended rats].

Objective. To observe the transition time of soleus I (TnI) isoforms and to elucidate the relationship between soleus TnI transition and atrophy; and to analyze the time course between testis atrophy and soleus atrophy. Method. Eight groups of male rats were suspended for 3, 4, 5, 7, 14, 21, 28 and 42 d, respectively. Besides, three groups of female rats were suspended for 3, 4 and 5 d respectively. Wet and relative weights (wet weight/body weight) of testis and soleus were measured. The expression of TnI was observed by Western blot. Result. The relative weight of soleus of tail-suspended male rats decreased significantly after 4 d of suspension as compared with control. The degree of rats soleus atrophy in the first 14 d of suspension was greater than that after 14 d. The relative weight of testis showed the same change as that of soleus. There was no significant change in the relative weight of soleus in 4 d of tail-suspended female rats. The significant decrease in the relative weight of tail-suspended female rats began on the 5th day. The Western blot showed that the transition from slow skeletal TnI (ssTnI) to fast skeletal TnI (fsTnI) in the soleus occurred in 14 d of tail-suspension. Conclusion. The overt atrophy of tail-suspended male rats occurs on the 4th day. The soleus TnI transition from ssTnI to fsTnI is on the 14th day. It is suggested that the TnI is not the sensitive protein to gravity. The overt atrophy of female tail-suspended rats occurs at the 5th day. This indicated that the decrease in testosterone level may accelerate the atrophy of the soleus.

Animals↗
PubMed2001

[Peripheral effector mechanism hypothesis on cardiovascular dysfunction after spaceflight].

In the years of 1990's, we systematically studied the adaptational changes in structure and function of both the heart and the vessels during simulated weightlessness. In our serial work, the tail-suspension rat model was used to simulate the microgravity-induced cephalad shift and redistribution of blood. On the basis of the facts we observed and the more recent advances in space and ground-based studies in 1990's, we put forward a hypothesis to offer a possible explanation for the frequent occurrence of postflight cardiovascular dysfunction. It states that, in addition to the factor of hypovolemia, the microgravity-induced adaptational changes in the structure and function of the two main effectors of the cardiovascular system, i.e., the arterial smooth muscle and the cardiac muscle might be one of the most important mechanisms accounting for postflight cardiovascular dysfunction.

Cardiovascular System↗
PubMed2000

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats.

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?

Animals↗
PubMed2000

Heat shock protein 70 expression in myocardium is blunted with simulated weightlessness.

Exposure of cardiac cells to a mild thermal or ischaemic stress, sufficient to induce HSP expression, protects them against a subsequent exposure to a more severe ischaemic stress. Over expression of HSPs by transfection of herpes simplex virus vectors in vitro or in transgenic animal in vivo can protect primary cardiac cells from subsequent exposure to severe thermal or hypoxic stress. The increases in myocardial and liver HSP70 accumulation in response to nonexertional heat stress are attenuated with senescence, and hearts from aged animals exhibit an impaired ability to produce the protective HSP. In our previous work, peculiar changes associated with aging, like lipofuscin accumulation and collagen deposition were shown in the myocardial tissue of long-term simulated weightless rats. We therefore designed the present study to examine whether the heat-stress induced HSP70 accumulation in myocardial tissue may decline with simulated weightlessness.

Animals↗
PubMed1999

[Echocardiographic assessment of left ventricular structure and function after simulated weightlessness in rats].

Objective. To investigate whether the changes in rat after simulated weightlessness are similar to those in astronaut after flight. Methods. The effects of 4 wk tail-suspension on left ventricular structure and function in rats were examined by echocardiography. Results. After 4 wk of simulated weightlessness, the thickness of both the anterior and posterior wall in left ventricle (LV) showed a general trend of decrease, but these changes were not statistically significant; the end-systolic and end-diastolic internal dimensions (ESD and EDD respectively) of LV decreased significantly; and the end-systolic volume, end-diastolic volume and stroke volume (ESV, EDV and SV respectively) were all reduced; so did the relevant indices of them. There were no significant differences in ejection fraction (EF) and fractional shortening (FS) between the tail-suspended and control groups. The left ventricular mass (LVM) and its index (LVMI) were decreased. The peak velocities of blood flow of aorta, pulmonary artery and mitral valve didn't show any significant change after simulated weightlessness. Conclusion. Medium-term simulated weightlessness may lead to a significant decrease in left ventricular internal dimension, ventricular volume, and mass, and a trend of decrease in mean left ventricular wall thickness. These changes in rats are similar to those observed in astronauts postflight.

Animals↗
PubMed1997

Time course and reversibility of arterial vasoreactivity changes in simulated microgravity rats.

Recent works have shown that postflight orthostatic intolerance involves multiple alterations in physiological function during actual or simulated microgravity. In our previous work, we demonstrated that 14-day tail-suspension resulted in an impaired ability of vascular smooth muscle to develop tension in arteries confined to the hindquarter, which have been suggested as an important factor accounting for the occurrence of orthostatic intolerance. To our knowledge, data on arterial vasoreactivity alterations induced by simulated microgravity longer than two weeks are not found. The aim of the present work was to characterize the time course of alterations in vasoconstrictor properties of hindquarter arteries during tail-suspension up to eight weeks, and to examine whether these alterations are reversible.

Adaptation, Physiological↗
PubMed1997

Plasticity of arterial vasculature during simulated weightlessness and its possible role in the genesis of postflight orthostatic intolerance.

Even after several decades of extensive research, the basic mechanism of postflight cardiovascular dysfunction has not yet been fully elucidated. It is now well recognized that multiple mechanisms might account for the frequent occurrence of significant postflight orthostatic intolerance. It has been found that all tissues adapt their design when exposed to sustained alteration in local activity and/or stress. The most obvious example is the musculo-skeletal system, structure and function of which might be severely affected during microgravity exposure. In an attempt to elucidate whether structure and function of cardiac and vascular smooth muscle might be affected by simulated by microgravity, a serial work was started several years ago. In this paper, we present our more recent findings on plasticity of arterial vasculature and its innervation state during and after simulated microgravity and its time course.

Adaptation, Physiological↗
PubMed1993

Localization of the potassium ion activation site in human liver fructose 1,6-bisphosphatase.

Three mouse monoclonal antibodies of human liver fructose 1,6-bisphosphatase are shown to bind to the enzyme at different sites as determined by ELISA. The binding of one of the monoclonal antibodies, L2E1, mimics the effects of K+ ions, including increase in the enzyme activity and enhancement of the sensitivity of the enzyme to AMP inhibition. We tentatively suggest that human liver FruP2ase may have a specific K+ activation site, which at least partially overlaps with the L2E1 binding region. This site has been localized by analyzing the peptide fragments formed by cleavage with cyanogen bromide.

Antibodies, Monoclonal↗
PubMed1992

[Uveitis and immune complexes].

The mean level of circulating immune complexes (CIC) in 24 uveitic patients determined by PEG deposition with the biochemical analyzor was found to be 28.458 +/- 7.796, in contrast to the value of 14.499 +/- 6.194 in the control group. The CIC level in acute iridocyclitis and panuveitis was significantly elevated compared with those in other types of uveitis. The results again demonstrated that most cases of uveitis, especially those of unknown origin, were related with immune complexes, and changes in the level of CIC could also be an indicator of therapeutic effects.

Adolescent↗