1 Department of Internal Medicine and 2 Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-8573
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Endurance exercise training increases the oxidative capacity of
skeletal muscles, reflecting the induction of genes encoding enzymes of
intermediary metabolism. To test the hypothesis that changes in gene
expression may be triggered specifically during recovery from
contractile activity, we quantified c-fos, B-crystallin, 70-kDa heat
shock protein (hsp70), myoglobin, and citrate synthase RNA in rabbit
tibialis anterior muscle during recovery from intermittent (8 h/day),
low-frequency (10 Hz) motor nerve stimulation. Recovery from a single
8-h bout of stimulation was characterized by large (>10-fold)
transient increases in c-fos,
B-crystallin, and hsp70 mRNA. Similar
changes were noted during recovery after 7 or 14 days of stimulation (8 h/day). Myoglobin and citrate synthase mRNA were also induced during
recovery, but the changes were of lesser magnitude (2- to 2.5-fold) and
were observed only following repeated bouts of muscle activity (7th or
14th day) that promoted sustained (>24 h) increases in these
transcripts. These findings indicate that recovery from exercise is
associated with specific transient changes in the expression of
immediate early and stress protein genes, suggesting that the products
of these genes may have specific roles in the remodeling process evoked
by repeated bouts of contractile activity.
exercise training; 70-kDa heat shock protein; myoglobin; citrate synthase; stress proteins
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
REGULARLY PERFORMED exercise, in addition to being an important component of preventative medicine, is beneficial in the treatment of diabetes, hyperlipidemia, hypertension, and other disorders (8). Many of the benefits derived from exercise training can be attributed to adaptations occurring specifically within skeletal muscle. However, despite extensive characterization of the training-induced changes in muscle substrate utilization, mitochondrial content, capillary density, and enzyme/contractile protein profiles (7, 16, 29, 33, 35, 36), surprisingly little information is available concerning the molecular events responsible for triggering and maintaining the adaptive process. For example, although it is clear that long-term adaptations require changes in gene expression, it is not known when the molecular stimulus to adapt is sensed by the myofiber (during or after exercise), how long the stimulus persists, or how repeated bouts of exercise produce incremental effects that ultimately characterize the trained state.
Direct evidence for regulation of gene expression specifically during recovery from exercise has recently been described for the GLUT-4 glucose transporter and hexokinase II genes (25, 27, 28). Transcription rate of the GLUT-4 gene in red skeletal muscle of rats was found to be increased by ~1.8-fold 3 h after exercise, a response that was not evident after 30 min or 24 h of recovery (25). Transient increases in hexokinase II mRNA and protein levels have also been found in gastrocnemius/plantaris muscles of rats during 24 h of recovery from exercise (28), a response that appears, at least in part, to be mediated by transcriptional activation of the hexokinase II gene both during and after exercise (27). These findings have led to the hypothesis that endurance training-induced adaptations in skeletal muscle may result from the cumulative effects of transient changes in gene expression induced during recovery from each exercise bout (36).
Increases in contractile activity also elicit a marked induction
(>10-fold) of a number of stress-related genes, including the
c-fos,
c-jun, and
egr-1 immediate early genes, the
70-kDa heat shock protein (hsp70)
and hsp60 heat shock genes, and the B-crystallin small-molecular-weight heat shock gene (23, 24, 26).
Although it remains to be determined whether the products of these
genes are required for downstream adaptive events in skeletal muscle,
their established roles as transcription factors and chaperone proteins
in other well-defined systems prompted us, in the present study, to
address the hypothesis that the expression of these genes may be
altered, not only during muscle exercise (23, 24, 26) but also during
recovery from contractile activity. We observed rapid, striking, and
transient increases in c-fos,
B-crystallin, and hsp70 mRNA
concentrations in rabbit tibialis anterior (TA) muscle specifically
during recovery from 8 h of low-frequency motor nerve stimulation
performed for 1, 7, or 14 days. These findings, therefore, provide
evidence that the adaptive responses of skeletal muscle to intermittent
contractile activity may be mediated, at least in part, by transient
changes in gene expression during recovery.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Materials. Adult New Zealand White rabbits (n = 61) weighing ~3.0 kg were purchased from Myrtles Rabbitry (Thompson Station, TN). All radiolabeled compounds were purchased from Amersham. All restriction enzymes and other chemicals were of molecular biology grade and purchased from either Promega, Life Technologies, or Sigma.
Animal surgery and stimulation protocol.
Rabbits were anesthetized by isoflurane inhalation. Under aseptic
conditions, electrodes were surgically placed in one hindlimb on either
side of the common peroneal nerve that innervates the TA and extensor
digitorum longus muscles of the lower leg. Leads from the electrodes
were attached to a microstimulator embedded in epoxy medium (gas
sterilized) and secured beneath the abdominal skin. Microstimulators
(32) were manufactured using a CMOS low-power, low-voltage LMC555CM
timer (Hamilton Hallmark), power switched via a low-power, low-voltage
CMOS D flipflop (Hamilton Hallmark), wired as a toggle flipflop,
deriving clock input from a Hex CMSO logic inverter with a Schmitt
trigger input (Hamilton Hallmark), which in turn derives its input from
a surface-mount NPN phototransistor (OPR5500, Optek) that permitted
noninvasive activation/deactivation of the stimulators. The
microstimulators were powered by a 3.0-V lithium battery and delivered
1-ms square wave pulses at a frequency of ~8 Hz. Rabbits were
stimulated for 8 h/day for either 1, 7, or 14 consecutive days. When
the final 8-h stimulation period was completed, the animals were killed
either immediately or after 1, 2, 4, 8, 16, or 24 h of rest. At the
time of death, the rabbits were anesthetized with pentobarbital sodium
(50 mg/kg, intravenous) and the stimulated TA muscle was surgically
removed, dissected free of connective tissue, frozen in liquid
nitrogen, and stored at 70°C. TA muscles from
noninstrumented naive rabbits served as controls. All protocols were
reviewed and approved by the Institutional Animal Care and Research
Advisory Committee and were conducted in accordance with the National
Institutes of Health "Guide for the Care and Use of Laboratory
Animals" [Department of Health and Human Services Publication
No. (NIH) 85-23, Revised 1985].
RNA isolation and Northern blot analysis.
TA muscle samples were powdered in liquid nitrogen using a precooled
(70°C) mortar and pestle. Total RNA was isolated from ~200
mg of powdered muscle by the guanidinium thiocyanate-phenol-chloroform extraction method (10) with the addition of an LiCl solubilization step
(30). Final RNA pellets were resuspended in deionized formamide, and
concentrations were determined spectrophotometrically (260 nm). Total
RNA (15 µg) was denatured and size fractionated in duplicate by gel
electrophoresis in 1.2% agarose gels containing 2.0 M formaldehyde. To
assess the quality and amount of RNA between sample lanes, the 28S and
18S ribosomal bands were visualized by ethidium bromide staining of the
gel using a charge-coupled device camera under ultraviolet
transillumination (Eagle Eye, Stratagene). The RNA was electroblotted
(Genie electrophoretic blotter, Idea Scientific) to Hybond N
(Amersham), cross-linked (Stratalinker, Stratagene), and prehybridized
at 42°C for 4 h in a solution of 50% deionized formamide, 4×
SSC (1× SSC = 150 mM sodium chloride, 15 mM sodium citrate),
5× Denhardt's solution (50× Denhardt's = 0.1% each
of bovine serum albumin, polyvinylpyrrolidone, and Ficoll), 0.1 mg/ml
yeast tRNA, 50 mM sodium phosphate (pH 7.0), 0.5 mg/ml sodium
pyrophosphate, and 1% sodium dodecyl sulfate (SDS). Hybridizations
were carried out overnight at 42°C using the appropriate
radiolabeled cDNA probe at 1-3 × 106
counts · min
1 · ml
1.
Details concerning the source and preparation of the different cDNA
probes used in the present study have been previously given (4, 23, 24,
26, 34). All cDNA probes were labeled with [
-32P]dATP (3,000 Ci/mmol) by random priming. After overnight hybridization, the
membranes were washed for 30 min in 0.1× SSC-0.1% SDS at room temperature, followed by 10 min at 50°C, and subjected to
autoradiography (2-24 h) using Kodak SAR-5 film with intensifying
screens. Each membrane was exposed to film for a minimum of three
different durations to ensure that nonsaturating signals were obtained. Signal intensity was quantified by densitometric scanning (Arcus II
scanner, AGFA) and image analysis software (Molecular Analyst, Bio-Rad), normalized to 28S rRNA (from ethidium bromide-stained gels)
to account for slight differences in loading between samples, and
expressed relative to 0-h recovery data (immediately after stimulation).
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
As an initial attempt to determine whether the adaptive response of skeletal muscle to daily periods of endurance activity may be associated with specific changes in gene expression occurring during recovery from contractile activity, we induced the TA muscle of rabbits, via continuous stimulation of the motor nerve, to contract for 8 h/day for 14 consecutive days. Northern blot analysis revealed a striking transient increase in c-fos and hsp70 mRNA concentrations, specifically during recovery from the final stimulation period (Fig. 1). Transcript levels for both genes were elevated within 2 h after the cessation of stimulation, continued to increase after 4 h, but returned to control levels by 24 h of recovery. Recovery also appeared to be associated with increases in myoglobin and citrate synthase mRNA content; however, these changes were of much smaller magnitude in the three sets of rabbits that completed the 14-day protocol.
|
To determine whether a single bout of contractile activity is sufficient to induce specific changes in gene expression during recovery, we performed Northern blot analysis on TA muscle obtained from naive rabbits subjected to 8 h of motor nerve stimulation followed by 0-24 h of recovery. Similar to recovery from 14 days of intermittent stimulation, both c-fos and hsp70 mRNA levels increased dramatically during recovery (Fig. 2). Peak expression of both transcripts, however, occurred after only 2 h of recovery and then declined rapidly, reaching control levels within 8 h. Interestingly, recovery from 8 h of stimulation also induced a marked increase in an unidentified higher-molecular-weight transcript that cross-hybridized with the c-fos cDNA probe. Gradual increases in wash stringency to 65°C progressively eliminated hybridization of the upper band, whereas hybridization to c-fos was maintained (data not shown), suggesting that the higher-molecular-weight band represents a unique mRNA species and is not simply a longer form of the c-fos mRNA.
|
Recovery from 8 h of stimulation was also associated with a dramatic
increase in the expression of B-crystallin mRNA, a
small-molecular-weight heat shock gene that is also markedly induced
within the first 24 h of continuous motor nerve stimulation (24).
B-crystallin mRNA levels increased rapidly during recovery and, in
contrast to the c-fos and hsp70 transcripts, remained elevated
throughout the entire 24-h recovery period (Fig. 2). It is important to
emphasize that, as with c-fos and hsp70,
B-crystallin mRNA levels
were not increased after 8 h of stimulation, indicating that the
induction of these genes was specific for the recovery period.
Transcript levels for myoglobin and citrate synthase were not
significantly altered during recovery from a single 8-h stimulation
bout.
In an effort to further characterize the gene-regulatory events that
may be occurring during the recovery phase following muscle activity,
we followed the expression pattern of the same set of genes in four
complete sets of rabbits stimulated for 8 h/day for 7 consecutive days.
Dramatic inductions (>10-fold) of c-fos, B-crystallin, and hsp70
mRNAs again were associated specifically with the first 2-4 h of
recovery from contractile activity (Figs. 3
amd 4). Similar to levels after both 1 and 14 days of stimulation, c-fos and hsp70 transcript levels rapidly
returned to baseline, whereas
B-crystallin mRNA remained elevated
during the entire 24-h recovery period. Recovery from stimulation also
appeared to be associated with a transient increase in myoglobin mRNA
content (Figs. 3 and 4), although these changes were relatively modest (~2.5-fold) and, thus, made it difficult to separate the potential responses during recovery from the generalized effect of 7 days of
intermittent stimulation (4.6-fold increase in myoglobin mRNA vs.
unstimulated controls). Citrate synthase mRNA levels were also elevated
in the TA muscle of all rabbits stimulated for 7 days (2.3-fold
increase vs. unstimulated controls), with no specific response evident
during recovery.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The findings from the present study demonstrate that recovery from
intermittent contractile activity is associated with transient increases in the expression of three potentially important genes: c-fos, an immediate early gene,
hsp70, the inducible member of the
70-kDa HSP family, and B-crystallin, a small-molecular-weight HSP.
Transcript levels for each of these genes increased by at least 10-fold
within 2-4 h after the cessation of contractile activity. The
c-fos and hsp70 mRNA levels returned to near control levels, whereas
B-crystallin mRNA remained elevated by approximately sixfold after
24 h of recovery.
The rapid and dramatic induction of these genes specifically during
recovery from contractile activity is of particular interest given the
cellular functions of these proteins. The c-Fos protein and members of
the Jun and activating transcription factor/adenosine 3',5'-cyclic
monophosphate response element binding protein families of nuclear
proteins collectively comprise the mammalian transcription factor AP-1
(12, 31). Heterodimer formation among these nuclear proteins generates a diverse array of protein complexes with similar DNA-binding specificity but distinct transcriptional control
properties. In addition, transcriptional activation by Fos-Jun
heterodimer complexes is specifically regulated by phosphorylation and
redox state (1, 2), two signaling mechanisms that may be operative in
skeletal myofibers (36). The hsp70 class of proteins serves as
molecular chaperones, facilitating the folding and intracellular compartmentalization of nascent proteins as well as stabilizing newly
denatured proteins (11, 14). B-crystallin, although originally
isolated as a specialized protein of the ocular lens (37), has recently
been identified as a tissue-specific HSP (18, 21, 22). Thus,
collectively, the functions of these proteins, as established in other
well-defined biological systems, are consistent with their
participation in adaptive remodeling processes within skeletal
myofibers, specifically, activation of gene transcription (c-Fos) and
stabilization of nascent proteins (hsp70 and
B-crystallin). Further
work will be required to establish the precise roles of these gene
products during the adaptive response to intermittent contractile
activity.
In contrast to the c-fos and
hsp70 genes, which are expressed at
low or undetectable levels under unstressed conditions, B-crystallin is constitutively expressed at high levels in tissues rich in mitochondria, including type I and IIa skeletal myofibers, heart, specific regions of the kidney, and the "ragged red fibers"
associated with skeletal muscle mitochondrial myopathies (5, 6, 13, 19,
20). The tissue-restricted expression of
B-crystallin and the
similar time frame of induction of
B-crystallin with c-fos and
hsp70 observed in the present study
suggest that expression of all three genes during recovery from
contractile activity is myofiber specific and does not stem from other
cell types present within muscle tissue (e.g., neural, capillary
endothelial, fibroblast cells).
It is interesting to note that c-fos,
B-crystallin, and hsp70 are also
induced in response to stimulation delivered continuously for 24 h/day
but with much different time courses;
c-fos, as well as two other immediate
early genes (c-jun and
egr-1), are markedly induced within 4 h after the onset of stimulation (23). However, after 8 h of
stimulation, expression of these immediate early genes is no longer
evident, suggesting that, in the present study, the daily induction of
c-fos expression during the first
2-4 h of recovery from stimulation may have been preceded by
transient inductions of the c-fos gene
during the 8-h stimulation periods. In contrast to
c-fos,
B-crystallin and
hsp70 transcript levels are not
consistently elevated during the first 8 h of stimulation but are
elevated by at least fivefold after 24 h of continuous stimulation (24,
26). The fact that
B-crystallin and
hsp70 were rapidly and dramatically
induced during the first 2-4 h of recovery from stimulation in the
present study raises the possibility that the signals triggering the
adaptive changes in gene expression may be facilitated by recovery and
delayed by continued contractile activity.
It is important to emphasize that skeletal muscle is composed of a
nonhomogenous mix of fiber types with distinct metabolic and
contractile properties. In the chronic nerve stimulation model, although stimulation is delivered to the peroneal nerve that innervates all fibers of the rabbit TA muscle, rapid declines in force output (50-60% within 15 min) suggest that there is a rapid loss in the number of fibers maintaining contractile activity (9, 17). The
fiber-type distribution of the rabbit TA muscle (~50% type IId
fast-twitch glycolytic, ~45% type I fast-twitch oxidative, and
~5% type I slow-twitch oxidative) (3, 15) strongly implies that only
subpopulations of fibers, presumably type I and IIa, are able to
maintain contractile activity during an 8-h stimulation period.
Interestingly, the initial induction of both B-crystallin and
hsp70 during the first 24 h of
continuous stimulation occurs specifically within the oxidative type I
and IIa myofibers and is not evident in type IId fibers until 21 days
after the onset of stimulation, suggesting that the fiber-specific
induction of
B-crystallin and hsp70
may mark those fibers that have initiated an adaptive response (23,
25). Although not directly addressed in the present study, it is likely
that the striking transient induction of the
c-fos,
B-crystallin, and
hsp70 genes observed during recovery
from daily bouts of contractile activity may also represent
fiber-type-specific regulation of these genes.
Additional evidence that recovery represents a period in which gene regulatory events are triggered during exercise training comes from recent work that has focused on genes that encode for proteins of intermediary metabolism. After 7 days of strenuous treadmill training (40 min/day, 8% grade, 32 m/min performed twice/day), transcription rate of the GLUT-4 glucose transporter gene in red skeletal muscle of rats was found to be no different from untrained rats 30 min after exercise, increased by 1.8-fold 3 h after exercise, but returned to control levels within 24 h after exercise (25). Similar transient increases in transcription of both the GLUT-4 and citrate synthase genes were also found during recovery from a single bout of treadmill exercise. O'Doherty et al. (27, 28) have reported that hexokinase II gene transcription, mRNA content, and enzyme activity are transiently increased in the gastrocnemius/plantaris muscle group of rats during 24 h of recovery from acute treadmill exercise. Moreover, the magnitude of hexokinase II induction was found to be directly related to the duration of exercise (28), suggesting that the intensity/duration of the contractile activity is an important determinant of the adaptive response during recovery.
How can transient changes in gene expression following exercise account for long-term, training-induced adaptations within skeletal muscle? The answer is likely to be found in the kinetics of protein synthesis and degradation. The time required to generate a specific change in a given gene product will be determined by the half-life (turnover rate) of the product of the rate-limiting step. When the stimulus to adapt is intermittent, as encountered during exercise training (3-7 days/wk), the net long-term change will reflect the cumulative effects of intermittent transient changes in expression of that gene product. Gene products with relatively long half-lives (mitochondrial proteins, contractile proteins) will show a small net increase from one training session to the next, whereas gene products with relatively short half-lives (immediate early genes) will not accumulate between training sessions. In the present study, although no consistent change during recovery was detected, average myoglobin and citrate synthase mRNA levels increased by ~2- to 4.5-fold after 7 days of intermittent stimulation, suggesting that the half-life for each of these transcripts is on the order of several days rather than hours. Further efforts to define the temporal sequence of the adaptive response to exercise training, perhaps through single fiber-type analysis, are likely to shed light on the molecular mechanisms regulating this physiologically important process.
![]() |
ACKNOWLEDGEMENTS |
---|
We gratefully acknowledge the expert surgical and technical assistance of Jie Liu and Donita Crippens.
![]() |
FOOTNOTES |
---|
This work was supported by National Heart, Lung, and Blood Institute Grants HL-07360 and HL-06296.
Present address for P. D. Neufer: John B. Pierce Laboratory, Yale University, 290 Congress Avenue, New Haven, CT 06519.
Address reprint requests to: R. S. Williams, Molecular Cardiology, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8573.
Received 6 June 1997; accepted in final form 15 October 1997.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Abate, C.,
S. J. Baker,
S. P. Lees-Miller,
C. W. Anderson,
D. R. Marshak,
and
T. Curran.
Dimerization and DNA binding alter phosphorylation of Fos and Jun.
Proc. Natl. Acad. Sci. USA
90:
6766-6770,
1993[Abstract].
2.
Abate, C.,
L. Patel,
F. D. Rauscher,
and
T. Curran.
Redox regulation of fos and jun DNA-binding activity in vitro.
Science
249:
1157-1161,
1990[Medline].
3.
Aigner, S.,
B. Gohlsch,
N. Hamalainen,
R. S. Staron,
A. Uber,
U. Wehrle,
and
D. Pette.
Fast myosin heavy chain diversity in skeletal muscles of the rabbit: heavy chain IId, not IIb predominates.
Eur. J. Biochem.
211:
367-372,
1993[Abstract].
4.
Annex, B. H.,
W. E. Kraus,
G. L. Dohm,
and
R. S. Williams.
Mitochondrial biogenesis in striated muscles: rapid induction of citrate synthase mRNA by nerve stimulation.
Am. J. Physiol.
260 (Cell Physiol. 29):
C266-C270,
1991
5.
Atomi, Y.,
S. Yamada,
R. Strohman,
and
Y. Nonomura.
Alpha B-crystallin in skeletal muscle: purification and localization.
J. Biochem. (Tokyo)
110:
812-822,
1991[Abstract].
6.
Bhat, S. P.,
and
C. N. Nagineni.
Alpha B subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues.
Biochem. Biophys. Res. Commun.
158:
319-325,
1989[Medline].
7.
Booth, F. W.,
and
D. B. Thomason.
Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models.
Physiol. Rev.
71:
541-585,
1991
8.
Booth, F. W.,
and
B. S. Tseng.
America needs to exercise for health.
Med. Sci. Sports Exerc.
27:
462-465,
1995[Medline].
9.
Cadefau, J. A.,
J. Parra,
R. Cusso,
G. Heine,
and
D. Pette.
Responses of fatigable and fatigue-resistant fibres of rabbit muscle to low-frequency stimulation.
Pflügers Arch.
424:
529-537,
1993[Medline].
10.
Chomczynski, P.,
and
N. Sacchi.
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal. Biochem.
162:
156-159,
1987[Medline].
11.
Craig, E. A.,
J. S. Weissman,
and
A. L. Horwich.
Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell.
Cell
78:
365-372,
1994[Medline].
12.
Curran, T.,
C. Abate,
S. Baker,
T. Kerppola,
and
S. Xanthoudakis.
The regulation of c-fos: too much is never enough.
Adv. Second Messenger Phosphoprotein Res.
28:
271-277,
1993[Medline].
13.
Dubin, R. A.,
E. F. Wawrousek,
and
J. Piatigorsky.
Expression of the murine alpha B-crystallin gene is not restricted to the lens.
Mol. Cell. Biol.
9:
1083-1091,
1989[Medline].
14.
Georgopoulos, C.,
and
W. J. Welch.
Role of the major heat shock proteins as molecular chaperones.
Annu. Rev. Cell Biol.
9:
601-634,
1993.
15.
Hamalainen, N.,
and
D. Pette.
The histochemical profiles of fast fiber types IIB, IID, and IIA in skeletal muscles of mouse, rat, and rabbit.
J. Histochem. Cytochem.
41:
733-743,
1993
16.
Henriksson, J.,
M. M. Chi,
C. S. Hintz,
D. A. Young,
K. K. Kaiser,
S. Salmons,
and
O. H. Lowry.
Chronic stimulation of mammalian muscle: changes in enzymes of six metabolic pathways.
Am. J. Physiol.
251 (Cell Physiol. 20):
C614-C632,
1986
17.
Hicks, A.,
K. Ohlendieck,
S. O. Gopel,
and
D. Pette.
Early functional and biochemical adaptations to low-frequency stimulation of rabbit fast-twitch muscle.
Am. J. Physiol.
273 (Cell Physiol. 42):
C297-C305,
1997
18.
Horwitz, J.
Alpha-crystallin can function as a molecular chaperone.
Proc. Natl. Acad. Sci. USA
89:
10449-10453,
1992[Abstract].
19.
Iwaki, T.,
A. Iwaki,
and
J. E. Goldman.
Alpha B-crystallin in oxidative muscle fibers and its accumulation in ragged-red fibers: a comparative immunohistochemical and histochemical study in human skeletal muscle.
Acta Neuropathol. (Berl.)
85:
475-480,
1993[Medline].
20.
Iwaki, T.,
A. Kume-Iwaki,
and
J. E. Goldman.
Cellular distribution of alpha B-crystallin in non-lenticular tissues.
J. Histochem. Cytochem.
38:
31-39,
1990[Abstract].
21.
Jakob, U.,
M. Gaestel,
K. Engel,
and
J. Buchner.
Small heat shock proteins are molecular chaperones.
J. Biol. Chem.
268:
1517-1520,
1993
22.
Klemenz, R.,
E. Frohli,
R. H. Steiger,
R. Schafer,
and
A. Aoyama.
Alpha B-crystallin is a small heat shock protein.
Proc. Natl. Acad. Sci. USA
88:
3652-3656,
1991[Abstract].
23.
Michel, J. B.,
G. A. Ordway,
J. A. Richardson,
and
R. S. Williams.
Biphasic induction of immediate early gene expression accompanies activity-dependent angiogenesis and myofiber remodeling of rabbit skeletal muscle.
J. Clin. Invest.
94:
277-285,
1994[Medline].
24.
Neufer, P. D.,
and
I. J. Benjamin.
Differential expression of B-crystallin and Hsp27 in skeletal muscle during continuous contractile activity. Relationship to myogenic regulatory factors.
J. Biol. Chem.
271:
24089-24095,
1996
25.
Neufer, P. D.,
and
G. L. Dohm.
Exercise induces a transient increase in transcription of the GLUT-4 gene in skeletal muscle.
Am. J. Physiol.
265 (Cell Physiol. 34):
C1597-C1603,
1993
26.
Neufer, P. D.,
G. A. Ordway,
G. A. Hand,
J. M. Shelton,
J. A. Richardson,
I. J. Benjamin,
and
R. S. Williams.
Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle.
Am. J. Physiol.
271 (Cell Physiol. 40):
C1828-C1837,
1996
27.
O'Doherty, R. M.,
D. P. Bracy,
D. K. Granner,
and
D. H. Wasserman.
Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise.
J. Appl. Physiol.
81:
789-793,
1996
28.
O'Doherty, R. M.,
D. P. Bracy,
H. Osawa,
D. H. Wasserman,
and
D. K. Granner.
Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise.
Am. J. Physiol.
266 (Endocrinol. Metab. 29):
E171-E178,
1994
29.
Pette, D.,
and
G. Vrbova.
Adaptation of mammalian skeletal muscle fibers to chronic electrical stimulation.
Rev. Physiol. Biochem. Pharmacol.
120:
115-202,
1992[Medline].
30.
Puissant, C.,
and
L. M. Houdebine.
An improvement of the single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Biotechniques
8:
148-149,
1990[Medline].
31.
Ransone, L. J.,
and
I. M. Verma.
Nuclear proto-oncogenes fos and jun.
Annu. Rev. Cell Biol.
6:
539-557,
1990.
32.
Salmons, S.,
and
G. Vrbova.
The influence of activity on some contractile characteristics of mammalian fast and slow muscles.
J. Physiol. (Lond.)
201:
535-549,
1969[Medline].
33.
Takahashi, M.,
and
D. A. Hood.
Chronic stimulation-induced changes in mitochondria and performance in rat skeletal muscle.
J. Appl. Physiol.
74:
934-941,
1993[Abstract].
34.
Underwood, L. E.,
and
R. S. Williams.
Pretranslational regulation of myoglobin gene expression.
Am. J. Physiol.
252 (Cell Physiol. 21):
C450-C453,
1987
35.
Williams, R. S.
Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event.
J. Biol. Chem.
261:
12390-12394,
1986
36.
Williams, R. S.,
and
P. D. Neufer.
Regulation of gene expression in skeletal muscle by contractile activity.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 12, chapt. 25, p. 1124-1150.
37.
Wistow, G. J.,
and
J. Piatigorsky.
Lens crystallins: the evolution and expression of proteins for a highly specialized tissue.
Annu. Rev. Biochem.
57:
479-504,
1988[Medline].