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1.
Previous studies in expression systems have found different ion activation of the Na+/K+-ATPase isozymes, which suggest that different muscles have different ion affinities. The rate of ATP hydrolysis was used
to quantify Na+,K+-ATPase activity, and the Na+ affinity of Na+,K+-ATPase was studied in total membranes from rat muscle and purified membranes from muscle with different fiber types. The
Na+ affinity was higher (K
m lower) in oxidative muscle compared with glycolytic muscle and in purified membranes from oxidative muscle compared with
glycolytic muscle. Na+,K+-ATPase isoform analysis implied that heterodimers containing the β1 isoform have a higher Na+ affinity than heterodimers containing the β2 isoform. Immunoprecipitation experiments demonstrated that dimers with α1 are responsible for approximately 36% of the total Na,K-ATPase activity. Selective inhibition of the α2 isoform with ouabain suggested that heterodimers containing the α1 isoform have a higher Na+ affinity than heterodimers containing the α2 isoform. The estimated K
m values for Na+ are 4.0, 5.5, 7.5 and 13 mM for α1β1, α2β1, α1β2 and α2β2, respectively. The affinity differences and isoform distributions imply that the degree of activation of Na+,K+-ATPase at physiological Na+ concentrations differs between muscles (oxidative and glycolytic) and between subcellular membrane domains with different
isoform compositions. These differences may have consequences for ion balance across the muscle membrane. 相似文献
2.
Isoform-Specific Function and Distribution of Na/K Pumps in the Frog Lens Epithelium 总被引:3,自引:1,他引:2
Epithelial cells from the anterior and equatorial surfaces of the frog lens were isolated and used the same day for studies
of the Na/K ATPase. RNase protection assays showed that all cells express α1- and α2-isoforms of the Na/K pump but not the α3-isoform, however the α2-isoform dominates in anterior cells whereas the α1-isoform dominates in equatorial cells. The whole cell patch-clamp technique was used to record functional properties of the
Na/K pump current (I
P
), defined as the current specifically inhibited by dihydro-ouabain (DHO). DHO-I
P
blockade data indicate the α1-isoform has a dissociation constant of 100 μm DHO whereas for the α2-isoform it is 0.75 μm DHO. Both α1- and α2-isoforms are half maximally activated at an intracellular Na+-concentration of 9 mm. The α1-isoform is half maximally activated at an extracellular K+-concentration of 3.9 mm whereas for the α2-isoform, half maximal activation occurs at 0.4 mm. Lastly, transport by the α1-isoform is inhibited by a drop in extracellular pH, which does not affect transport by the α2-isoform. Under normal physiological conditions, I
P
in equatorial cells is approximately 0.23 μA/μF, and in anterior cells it is about 0.14 μA/μF. These current densities refer
to the area of cell membrane assuming a capacitance of around 1 μF/cm2. Because cell size and geometry are different at the equatorial vs. anterior surface of the intact lens, we estimate Na/K pump current density per area of lens surface to be around 10 μA/cm2 at the equator vs. 0.5 μA/cm2 at the anterior pole.
Received: 17 May 2000/Revised: 11 August 2000 相似文献
3.
Hamstring strain rehabilitation programs with an eccentric bias are effective but have a low adherence rate. Post-stretch isometric (PS-ISO) contractions which incorporate a highly controlled eccentric contraction followed by an isometric contraction resulting in elevated torque during following stretch, compared with isometric contractions at the same joint angle. This study measured torque, activation and musculotendinous unit behaviour of the hamstrings during PS-ISO contractions of maximal and submaximal levels using two stretch amplitudes. Ten male participants (24.6 years ± 2.22 years) completed maximal and submaximal baseline isometric contractions at 90°, 120° and 150° knee flexion and PS-ISO contractions of maximal and submaximal intensity initiated at 90° and 120° incorporating active stretch of 30° and 60° at 60°·s−1. Torque and muscle activation of the knee flexors were simultaneously recorded. Musculotendinous unit behaviour of the biceps femoris long head was recorded via ultrasound during all PS-ISO contractions. Compared with baseline, torque was 8% and 39% greater in the maximal and submaximal PS-ISO conditions respectively with no change in muscle activation. The biceps femoris long head muscle lengthened during all PS-ISO contractions. PS-ISO contractions may be beneficial where the effects of highly controlled eccentric contractions and elevated isometric torque are desired, such as hamstring rehabilitation. 相似文献
4.
A partially purified preparation of the lobster muscle Na+/Ca2+ exchanger was reconstituted with, presumably, random orientation in liposomes. Ca2+ efflux from 45Ca-loaded vesicles was studied in exchanger molecules in which the transporter cytoplasmic surface was exposed to the extravesicular
(ev) medium. Extravesicular Na+ (Na
ev
)-dependent Ca2+ efflux depended directly upon the extravesicular Ca2+ concentration ([Ca2+]
ev
) with a half-maximal activation at [Ca2+]
ev
= 0.6 μm. This suggests that the lobster muscle exchanger is catalytically upregulated by cytoplasmic Ca2+, as in most other species. In contrast, at low [Na+]
ev
, the Ca
ev
-binding site (i.e., on the cytoplasmic surface) for Ca2+ transported via Ca2+/Ca2+ exchange was half-maximally activated by about 7.5 μm Ca2+. Mild proteolysis of the Na+/Ca2+ exchanger by α-chymotrypsin also upregulated the Na
ev
-dependent Ca2+ efflux. Following proteolytic digestion in Ca-free medium, the exchanger was no longer regulated by nontransported ev Ca2+. Proteolytic digestion in the presence of 1.9 μm free ev Ca2+, however, induced only a 1.6-fold augmentation of Ca2+ efflux, whereas, after digestion in nominally Ca-free medium, a 2.3-fold augmentation was observed; Ca2+ also inhibited proteolytic degradation of the Na+/Ca2+ exchanger measured by immunoblotting. These data suggest that Ca2+, bound to a high affinity binding site, protects against the activation of the Na+/Ca2+ exchanger by α-chymotrypsin. Additionally, we observed a 6-fold increase in the Na+/Ca2+ exchange rate, on average, when the intra- and extravesicular salt concentrations were increased from 160 to 450 mm, suggesting that the lobster muscle exchanger is optimized for transport at the high salt concentration present in lobster
body fluids.
Received: 20 October 1999/Revised: 13 January 2000 相似文献
5.
The yeastRhodotorula glutinis was found to transport amino acids against a concentration gradient (100∶1 for 10−6
m l-lysine and 1500∶1 for 10−6
m α-aminoisobutyric acid). Anaerobically, the concentration gradients of free amino acids were occasionally higher than aerobically.
The influx is saturable with an apparentK
m of 1mm forl-lysine and 2mm for α-aminoisobutyric acid. The pH optimum for AIB uptake was 5.0, the apparent activation energy between 5° and 30° was
13,200 cal/mole. Competition of an asymmetric nature among various amino acids for uptake was observed. Intracellular amino
acids did not leave the cell under any conditions of incubation, short of breaking up the plasma membrane, but they showed
a powerful “trans” inhibitory effect on the uptake of amino acids. 相似文献
6.
Other than the fact that the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel can be activated by cAMP dependent kinase (PKA), little is known about the signal transduction pathways regulating
CFTR. Since G-proteins play a principal role in signal transduction regulating several ion channels [4, 5, 9], we sought to
test whether G-proteins control CFTR Cl− conductance (CFTR G
Cl
) in the native sweat duct (SD). We permeabilized the basolateral membrane with α-toxin so as to manipulate cytosolic nucleotides.
We activated G-proteins and monitored CFTR G
Cl
activity as described earlier [20, 23, 25]. We now show that activating G-proteins with GTP-γ-S (100 μm) also activates CFTR G
Cl
in the presence of 5 mm ATP alone (without exogenous cAMP). GTP-γ-S increased CFTR G
Cl
by 44 ± 20 mS/cm2 (mean ±se; n= 7). GDP (10 mm) inhibited G-protein activation of CFTR G
Cl
even in the presence of GTP-γ-S. The heterotrimeric G-protein activator (AlF4
−) in the cytoplasmic bath activated CFTR G
Cl
(increased by 51.5 ± 9.4 mS/cm2 in the presence of 5 mm ATP without cAMP, n= 6), the magnitude of which was similar to that induced by GTP-γ-S. Employing immunocytochemical-labeling techniques, we
localized Gαs, Gαi, Gαq, and Gβ at the apical membranes of the sweat duct. Further, we showed that the mutant CFTR G
Cl
in ducts from cystic fibrosis (CF) subjects could be partially activated by G-proteins. The magnitude of mutant CFTR G
Cl
activation by G-proteins was smaller as compared to non-CF ducts but comparable to that induced by cAMP in CF ducts. We conclude
that heterotrimeric G-proteins are present in the apical membrane of the native human sweat duct which may help regulate salt
absorption by controlling CFTR G
Cl
activity.
Received: 9 June 2000/Revised: 5 October 2000 相似文献
7.
Guennoun-Lehmann S Fonseca JE Horisberger JD Rakowski RF 《The Journal of membrane biology》2007,216(2-3):107-116
Palytoxin (PTX) opens a pathway for ions to pass through Na,K-ATPase. We investigate here whether PTX also acts on nongastric
H,K-ATPases. The following combinations of cRNA were expressed in Xenopus laevis oocytes: Bufo marinus bladder H,K-ATPase α2- and Na,K-ATPase β2-subunits; Bufo Na,K-ATPase α1- and Na,K-ATPase β2-subunits; and Bufo Na,K-ATPase β2-subunit alone. The response to PTX was measured after blocking endogenous Xenopus Na,K-ATPase with 10 μm ouabain. Functional expression was confirmed by measuring 86Rb uptake. PTX (5 nm) produced a large increase of membrane conductance in oocytes expressing Bufo Na,K-ATPase, but no significant increase occurred in oocytes expressing Bufo H,K-ATPase or in those injected with Bufo β2-subunit alone. Expression of the following combinations of cDNA was investigated in HeLa cells: rat colonic H,K-ATPase α1-subunit and Na,K-ATPase β1-subunit; rat Na,K-ATPase α2-subunit and Na,K-ATPase β2-subunit; and rat Na,K-ATPase β1- or Na,K-ATPase β2-subunit alone. Measurement of increases in 86Rb uptake confirmed that both rat Na,K and H,K pumps were functional in HeLa cells expressing rat colonic HKα1/NKβ1 and NKα2/NKβ2. Whole-cell patch-clamp measurements in HeLa cells expressing rat colonic HKα1/NKβ1 exposed to 100 nm PTX showed no significant increase of membrane current, and there was no membrane conductance increase in HeLa cells transfected
with rat NKβ1- or rat NKβ2-subunit alone. However, in HeLa cells expressing rat NKα2/NKβ2, outward current was observed after pump activation by 20 mm K+ and a large membrane conductance increase occurred after 100 nm PTX. We conclude that nongastric H,K-ATPases are not sensitive to PTX when expressed in these cells, whereas PTX does act
on Na,K-ATPase. 相似文献
8.
According to the equilibrium point theory, the control of posture and movement involves the setting of equilibrium joint positions
(EP) and the independent modulation of stiffness. One model of EP control, the α-model, posits that stable EPs and stiffness
are set open-loop, i.e. without the aid of feedback. The purpose of the present study was to explore for the elbow joint the
range over which stable EPs can be set open-loop and to investigate the effect of co-contraction on intrinsic low-frequency
elbow joint stiffness (K
ilf). For this purpose, a model of the upper and lower arm was constructed, equipped with Hill-type muscles. At a constant neural
input, the isometric force of the contractile element of the muscles depended on both the myofilamentary overlap and the effect
of sarcomere length on the sensitivity of myofilaments to [Ca2+] (LDCS). The musculoskeletal model, for which the parameters were chosen carefully on the basis of physiological literature,
captured the salient isometric properties of the muscles spanning the elbow joint. It was found that stable open-loop EPs
could be achieved over the whole range of motion of the elbow joint and that K
ilf, which ranged from 18 to 42 N m·rad−1, could be independently controlled. In the model, LDCS contributed substantially to K
ilf (up to 25 N m·rad−1) and caused K
ilf to peak at a sub-maximal level of co-contraction. 相似文献
9.
Yu-Guang Ma Ling Dong Xiao-Long Ye Chang-Lei Deng Jiu-Hua Cheng Wen-Chao Liu Jin Ma Yao-Ming Chang Man-Jiang Xie 《Apoptosis : an international journal on programmed cell death》2010,15(4):426-438
The large conductance Ca2+-activated K+ (BKCa) channels are highly expressed in vascular smooth muscle cells (VSMCs) and play an essential role in the regulation of various
physiological functions. Besides its electrophysiological function in vascular relaxation, BKCa has also been reported to be implicated in nitric oxide (NO)-induced apoptosis of VSMCs. However, the molecular mechanism
is not clear and has not been determined on cloned channels. The present study was designed to clarify whether activation
of cloned BKCa channel was involved in NO-induced apoptosis in human embryonic kidney 293 (HEK293) cell. The cDNA encoding the α-subunit
of BKCa channel, hSloα, was transiently transfected into HEK293 cells. The apoptotic death in HEK-hSloα cells was detected using immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, MTT test, and flow
cytometry assays. Whole-cell and single-channel characteristics of HEK-hSloα cells exhibited functional features similar to native BKCa channel in VSMCs. Exposuring of HEK- hSloα cells to S-nitroso-N-acetyl-penicillamine increased the hSloα channel activities of whole-cell and single-channel, and then increased percentage of cells undergoing apoptosis. However,
blocking hSloα channels with 1 mM tetraethylammonia or 100 nM iberiotoxin significantly decreased the NO-induced apoptosis, whereas 30 μM
NS1619, the specific agonist of BKCa, independently increased hSloα currents and induced apoptosis. These results indicated that activation of cloned BKCa channel was involved in NO-induced apoptosis of HEK293 cells. 相似文献
10.
Masłyk M Kochanowicz E Zieliński R Kubiński K Hellman U Szyszka R 《Molecular and cellular biochemistry》2008,312(1-2):61-69
Since Svf1 is phosphoprotein, we investigated whether it was a substrate for protein kinase CK2. According to the amino acid
sequence Svf1 harbours 20 putative CK2 phosphorylation sites. Here, we have reported cloning, overexpression, purification
and characterization of yeast Svf1 as a substrate for three forms of yeast CK2. Svf1 serves as a substrate for both the recombinant
CK2α (K
m 0.35 μM) and CK2α′ (K
m 0.18 μM) as well as CK2 holoenzyme (K
m 1.1 μM). Different K
m values argue that CK2β(β′) subunit has an inhibitory effect on the activity of both CK2α and CK2α′ towards surviving factor
Svf1. Reconstitution of α′2ββ′ isoform of CK2 holoenzyme shows that β/β′ subunits have regulatory effect depending on the kind of CK2 catalytic subunit.
This effect was not observed in the case of α2ββ′ isoform, which may be due to interaction between Svf1 and regulatory CK2β subunit (shown by co-immunoprecipitation experiments).
Interactions between CK2 subunits and Svf1 protein may have influence on ATP as well as ATP-competitive inhibitors (TBBt and
TBBz) binding. CK2 phosphorylates up to six serine residues in highly acidic peptide K199EVIPESDEEESSADEDDNEDEDEESGDSEEESGSEEESDSEEVEITYED248 of the Svf1 protein in vitro. Presented data may help to elucidate the role of protein kinase CK2 and Svf1 in the regulation
of cell survival pathways. 相似文献
11.
Generally the number of muscles acting across a joint exceeds the number of degrees of freedom available to the joint. This redundancy raises a problem regarding the ratio in which these muscles are activated during a particular motor task. In this paper we present a theory to explain the activation patterns of muscles used during voluntary and reflex induced contractions. The basic assumptions underlying the theory are that 1) coordination of muscles is based on synergistic muscle activities, 2) the synergisms involved satisfy certain transformations of muscle spindle signals to muscle activation signals and 3) muscle spindle output is proportional to the ratio of muscle stretch and muscle length in lengthening muscles, and is zero in shortening muscles. The theory is used to predict the recruitment threshold of motor units in six arm muscles during voluntary isometric contractions. All theoretical predictions are in reasonable agreement with the experimentally observed behavior of a large population of motor units within each muscle. However, within a single muscle sometimes motor-unit populations have been found to have different types of recruitment behavior. This deviating behavior is discussed in the light of the theory presented here. 相似文献
12.
The individual components of the backbone 15N CSA tensor, σ11, σ22, σ33, and the orientation of σ11 relative to the NH bond described by the angle β have been determined for uniformly labeled 15N, 13C ubiquitin from partial alignment in phospholipid bicelles, Pf1 phage, and poly(ethylene glycol) by measuring the residue-specific residual dipolar couplings and chemical shift deviations. No strong correlation between any of the CSA tensor components is observed with any single structural feature. However, the experimentally determined tensor components agree with the previously determined average CSA principal components [Cornilescu and Bax (2000) J. Am. Chem. Soc. 122, 10143–10154]. Significant deviations from the averages coincide with residues in β-strand or extended regions, while α-helical residue tensor components cluster close to the average values.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
13.
Photosynthetic parameters of phytoplankton and sea ice algae from landfast sea ice of the Chukchi Sea off Point Barrow, Alaska,
were assessed in spring 2005 and winter through spring 2006 using Pulse Amplitude Modulated (PAM) fluorometry including estimates
of maximum quantum efficiency (F
v/F
m), maximum relative electron transport rate (rETRmax), photosynthetic efficiency (α), and the photoadaptive index (E
k). The use of centrifuged brine samples allowed to document vertical gradients in ice algal acclimation with 5 cm vertical
resolution for the first time. Bottom ice algae (0–5 cm from ice–water interface) expressed low F
v/F
m (0.331–0.426) and low α (0.098–0.130 (μmol photons m−2s−1)−1) in December. F
v/F
m and α increased in March and May (0.468–0.588 and 0.141–0.438 (μmol photons m−2s−1)−1, respectively) indicating increased photosynthetic activity. In addition, increases in rETRmax (3.3–16.4 a.u.) and E
k (20–88 μmol photons m−2 s−1) from December to May illustrates a higher potential for primary productivity as communities become better acclimated to
under-ice light conditions. In conclusion, photosynthetic performance by ice algae (as assessed by PAM fluorometry) was tightly
linked to sea ice salinity, temperature, and inorganic nutrient concentrations (mainly nitrogen). 相似文献
14.
Variation of chromophoric dissolved organic matter and possible attenuation depth of ultraviolet radiation in Yunnan Plateau lakes 总被引:2,自引:0,他引:2
The increase of ultraviolet radiation (UVR, 280–400 nm) caused by stratospheric ozone depletion has profound effects on aquatic
ecosystems. High-altitude lakes in the Yunnan Plateau are exposed to high intensities of UVR and contain low concentrations
of chromophoric dissolved organic matter (CDOM). Thirty-eight lakes in the Yunnan Plateau with elevations from 1291 to 3809
m above sea level were investigated to study CDOM concentrations and possible effects of UVR on the lake ecosystem. The attenuation
of UVR in the Yunnan Plateau lakes was calculated from the absorption coefficient of CDOM based on an empirical relationship
from lakes in the Alps and Pyrenees mountains. Absorption coefficients [α(λ)] at 320 nm [α(320)] ranged from 0.52 to 14.05 m−1 (mean ± standard deviation, 4.40 ± 3.85 m−1) and at 380 nm [α(380)] from 0.05 to 4.51 m−1 (1.40 ± 1.30 m−1). The exponential slope coefficient for the relationship of wavelength to α(λ) ranged from 16.2 to 41.4 μm−1 (21.74 ± 4.93 μm−1) over the 280–400 nm interval. Normalized fluorescence emission (NFLU) at 450 nm from an excitation wavelength of 355 nm,
F
n(355), averaged 7.93 ± 3.22 NFLU. A significant positive relationship was found between α(355) and F
n(355). The estimated diffuse attenuation coefficients of UV-B (320 nm) and UV-A (380 nm) ranged from 0.55 to 15.77 m−1 and from 0.24 to 6.73 m−1; the corresponding 1% attenuation depths ranged from 0.29 to 8.44 m and from 0.68 to 19.12 m. Twenty-five of 38 lakes had
1% UV-B attenuation depths of 1.5 m or more. The median 1% attenuation depth was 28.8% of the sampling depth for UV-B radiation
and 60% for UV-A. In addition to CDOM, chlorophyll α (Chla) and total suspended matter (TSM) also may contribute to attenuation of UVR. 相似文献
15.
Oxidative stress is a putative factor responsible for reducing function and increasing apoptotic signaling in skeletal muscle with aging. This study examined the contribution and functional significance of the xanthine oxidase enzyme as a potential source of oxidant production in aged skeletal muscle during repetitive in situ electrically stimulated isometric contractions. Xanthine oxidase activity was inhibited in young adult and aged mice via a subcutaneously placed time-release (2.5 mg/day) allopurinol pellet, 7 days before the start of in situ electrically stimulated isometric contractions. Gastrocnemius muscles were electrically activated with 20 maximal contractions for 3 consecutive days. Xanthine oxidase activity was 65% greater in the gastrocnemius muscle of aged mice compared to young mice. Xanthine oxidase activity also increased after in situ electrically stimulated isometric contractions in muscles from both young (33%) and aged (28%) mice, relative to contralateral noncontracted muscles. Allopurinol attenuated the exercise-induced increase in oxidative stress, but it did not affect the elevated basal level of oxidative stress that was associated with aging. In addition, inhibition of xanthine oxidase activity decreased caspase-3 activity, but it had no effect on other markers of mitochondrial-associated apoptosis. Our results show that compared to control conditions, suppression of xanthine oxidase activity by allopurinol reduced xanthine oxidase activity, H2O2 levels, lipid peroxidation, and caspase-3 activity; prevented the in situ electrically stimulated isometric contraction-induced loss of glutathione; prevented the increase in catalase and copper-zinc superoxide dismutase activities; and increased maximal isometric force in the plantar flexor muscles of aged mice after repetitive electrically evoked contractions. 相似文献
16.
E. A. Turovsky M. V. Turovskaya A. V. Berezhnov A. V. Tolmacheva N. P. Kaimachnikov L. P. Dolgacheva V. P. Zinchenko E. I. Maevskii V. V. Dynnik 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2012,6(1):35-44
Experiments on cultured mouse adipocytes (9 days in vitro) using fluorescent microscopy have shown that activation of α1- and α2-adrenoceptors by norepinephrine (NE) or α2-adrenoreceptors by L-arginine evokes transient Ca2+ signals, while activation of m3-cholinoreceptors by acetylcholine (ACh) or betaine causes sustained or damped Ca2+ oscillations. The presence in the incubation medium of L-arginine at a low concentration (100–200 μM) is necessary for a vigorous manifestation of these effects, apparently due to
transition of protein kinase G (PKG) and phosphodiesterase V into an active state. In the presence of 1–10 mM L-arginine, the amplitude of the Ca2+ transient response to NE increases and signal duration decreases. ACh and NE upon a sequential addition mutually potentiate
their effects. Using an inhibitory analysis we show that the observed modes are related to the operation of a signaling pathway
with the participation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB), endothelial NO synthase (eNOS), cytoplasmic
guanylate cyclase (sGC), protein kinase G (PKG), ADP-ribosyl cyclase (CD38), and the ryanodine receptor (RyR). The formation
of several loops of positive feedbacks (PF) and negative feedbacks (NF) in the signaling system is possible: (i) short PF
loops due to Ca2+-induced Ca2+ release (CICR) from internal stores through the inositol trisphosphate receptor (IP3R) and RyR participating in the transient signal formation; (ii) long PF loop Ca2+ → eNOS → sGC → PKG → CD38 → RyR → Ca2+, which can provide necessary conditions for calcium oscillations arising from short PF loops (CICR); (iii) several NF loops
based on PKG-mediated inhibition of IP3R and activation of Ca2+-ATPases of sarco(endo)plasmic reticulum and of the plasma membrane providing a shutdown of signaling by the pathway phospholipase
C → IP3R → Ca2+ and limiting Ca2+ rise caused by the pathway PI3K → PKB → eNOS → sGC → PKG → CD38 → RyR → Ca2+. Convergence of signaling pathways that involve α1-, α2-, and m3-receptors and then Gβγ-subunits of Gq and Gq proteins acting on PI3Kγ can provide activation of cytoplasmic PKG, which plays a key role in producing transient responses,
in activation of Ca2+ removal and generation of [Ca2+]i oscillations. PKG inhibition (implemented here by KT5823 application) in the presence of any agonist results in rupture of
NF loops controlling Ca2+ transporting systems activity that leads to uncontrolled [Ca2+]i rise and cell death. 相似文献
17.
K. B. Athreya 《Journal of mathematical biology》1992,30(6):577-581
If qk is the extinction probability of a slightly supercritical branching process with offspring distribution P
kr
: r = 0, 1, 2,..., then it is shown that if sup r
r
3
p
kr
, < , inf 2
k > 0, and m
k
1, then 1 – q
k
2(m
k
–1)
k
–2, where m
k
=
r
rp
kr
, 2
k
= k
r
r
2
p
kr
– m
k
2. This provides a simple set of sufficient conditions for the validity of a conjecture of Ewens (1969) for the survival probability of a slightly advantageous mutant gene.Research supported in part by NSF grants DMS-8803639 and DMS-9007182 相似文献
18.
Veronique Maes Dirk Tourwé 《International journal of peptide research and therapeutics》2006,12(3):197-202
The retro-N
α-carboxymethyl histidine moiety, short (N
αHis)Ac, functions as an efficient chelator for the 99mTc(CO)3 core which allows the labeling of the peptides with a very high specific activity. However as a general consequence of the neutral [99mTc(CO)3] (N
αHis)Ac-complex, undesired accumulation in kidney and liver may be high. In order to improve the pharmacokinetic properties of the radiolabeled peptides containing this chelate, attempts have been made to conjugate a carbohydrate using the Maillard reaction. Since the (N
αHis)Ac moiety has an unusually reactive N
α, various chemical strategies have been explored to perform the Maillard reaction followed by the Amadori rearrangement on peptides containing this chelator. This indicated that a selective protection of the secondary nitrogen in the chelator is necessary.Australian Peptide Conference Issue. 相似文献
19.
It has been known for a long time that the steady-state isometric force after muscle stretch is bigger than the corresponding force obtained in a purely isometric contraction for electrically stimulated and maximal voluntary contractions (MVC). Recent studies using sub-maximal voluntary contractions showed that force enhancement only occurred in a sub-group of subjects suggesting that force enhancement for sub-maximal voluntary contractions has properties different from those of electrically-induced and maximal voluntary contractions. Specifically, force enhancement for sub-maximal voluntary contractions may contain an activation-dependent component that is independent of muscle stretching. To address this hypothesis, we tested for force enhancement using (i) sub-maximal electrically-induced contractions and stretch and (ii) using various activation levels preceding an isometric reference contraction at 30% of MVC (no stretch). All tests were performed on human adductor pollicis muscles. Force enhancement following stretching was found for all subjects (n = 10) and all activation levels (10%, 30%, and 60% of MVC) for electrically-induced contractions. In contrast, force enhancement at 30% of MVC, preceded by 6 s of 10%, 60%, and 100% of MVC was only found in a sub-set of the subjects and only for the 60% and 100% conditions. This result suggests that there is an activation-dependent force enhancement for some subjects for sub-maximal voluntary contractions. This activation-dependent force enhancement was always smaller than the stretch-induced force enhancement obtained at the corresponding activation levels. Active muscle stretching increased the force enhancement in all subjects, independent whether they showed activation dependence or not. It appears that post-activation potentiation, and the associated phosphorylation of the myosin light chains, might account for the stretch-independent force enhancement observed here. 相似文献
20.
Apoptosis has been implicated in mediating denervation-induced muscle wasting. In this study we determined the effect of interference
of apoptosis on muscle wasting during denervation by using mice genetically deficient in pro-apoptotic Bax. After denervation,
muscle wasting was evident in both wild-type and Bax−/− muscles but reduction of muscle weight was attenuated in Bax−/− mice. Apoptotic DNA fragmentation increased in wild-type denervated muscles whereas there was no statistical increase in
DNA fragmentation in denervated muscles from Bax−/− mice. Mitochondrial AIF and Smac/DIABLO releases and Bcl-2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a
similar extent in muscles from wild-type and Bax−/− mice following denervation. Mitochondrial cytochrome c release was elevated in denervated muscles from wild-type mice but the increase was suppressed in muscles from Bax−/− mice. Increases in caspase-3 and -9 activities and oxidative stress markers H2O2, MDA/4-HAE and nitrotyrosine were all evident in denervated muscles from wild-type mice but these changes were absent in
muscles from Bax−/− mice. Moreover, ARC increased exclusively in denervated Bax−/− muscle. Our data indicate that under conditions of denervation, pro-apoptotic signalling is suppressed and muscle wasting
is attenuated when the Bax gene is lacking. These findings suggest that interventions targeting apoptosis may be valuable
in ameliorating denervation-associated pathologic muscle wasting in certain neuromuscular disorders that involve partial or
full denervation. 相似文献