Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histochemical profiles of myofibrillar adenosine triphosphatase (ATPase), nicotinamide adenine dinucleotide diaphorase (NADDase), and phosphorylase (Pase) activities were studied in the respiratory muscles of the chicken. Most respiratory muscles contained fibers exhibiting 18 possible combinations of staining reactions (dark or light ATPase; dark, intermediate, or light NADDase; dark, intermediate, or light Pase). Fibers that stained light for ATPase constituted as little as 10% of the total population in rectus abdominis, but as much as 32% of the total in costosternalis pars major. Those fibers did not tend to be smaller than fibers that stained dark for ATPase in the respiratory muscles as a group. Assuming these staining characteristics are correlated with functional properties of the fibers, as they are in mammals, the majority of the fibers should contract rapidly (dark ATPase) and be fatigue resistant (dark and intermediate NADDase).
 ...
PMID:Histochemical studies of respiratory muscles of chicken. 14 96

A reexamination of the question of specificity of reinnervation of fast and slow muscle was undertaken using the original "self" nerve supply to the fast lateral gastrocnemius (LG) and slow soleus muscles in the rat hindlimb. This paradigm takes advantage of the unusual situation of a common nerve branch, which supplies both a fast and slow muscle, and of the opportunity to keep the reinnervating nerve in its normal position. In addition it provides a test of the effects of cross-reinnervation among muscles of the same functional group. The properties of soleus and LG muscles and of individual muscle units were characterized in normal rats and in rats 4-14 mo after cutting the lateral gastrocnemius-soleus (LGS) nerve and suture of the proximal stump to the dorsal surface of the LG muscle. Individual muscle units were functionally isolated by stimulation of single motor axons to LG or soleus muscle contained in teased filaments in the L4 and L5 ventral roots. Motor units were classified as fast contracting fatiguable (FF), fast contracting fatigue resistant (FR), and slow (S) on the basis of criteria described in the cat by Burke et al. and applied to rat muscle units by Gillespie et al. Muscle fibers were classified as fast glycolytic (FG), fast oxidative glycolytic (FOG), and slow oxidative (SO) on the basis of histochemical staining for myosin ATPase, nicotinamide-adenine dinucleotide diaphorase (NADH-D), and alpha-glycerophosphate (alpha-GPD). Reinnervated muscles developed less force and weighed less in accordance with having fewer than normal motor units and having lost denervated muscle fibers. Normal LG contained a small proportion of S-type motor units (9%), whereas the majority (80%) of control soleus units were S type. After reinnervation, each muscle contained similar proportions of fast and slow motor units with S-type units constituting 30% of units in both muscles. When compared with the normal motor-unit sample, there was no significant change in average twitch and tetanic force in reinnervated muscles for each type of motor unit. However, the range within each type was greater, and there was considerable overlap between types. Twitch contraction time was inversely correlated with force in normal and reinnervated muscles as shown previously in self- and cross-reinnervated LGS in the cat. Changes in proportions of motor units in reinnervated LG were accompanied by corresponding changes in histochemical muscle types. This contrasted with reinnervated soleus in which the proportion of muscle fiber types was not significantly changed from normal despite significant change in motor-unit proportions.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Motor units and histochemistry in rat lateral gastrocnemius and soleus muscles: evidence for dissociation of physiological and histochemical properties after reinnervation. 295 72

This work tested whether the membrane electrical properties of cat motoneurons, the contractile properties of their muscle units, and the normal relationships among them would be restored 9 mo after section and resuture of their muscle nerve. Properties of medial gastrocnemius (MG) motor units were examined 9 mo following section and resuture of the MG nerve in adult cats. Motoneuron electrical properties and muscle-unit contractile properties were measured. Motor units were classified on the basis of their contractile properties as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (8, 20). Muscle fibers were classified as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) on the basis of histochemical staining for myosin adenosine triphosphatase, nicotinamide adenine dinucleotide diaphorase, and alpha-glycerophosphate dehydrogenase (48). Following 9 mo self-reinnervation, the proportions of each motor-unit type were the same as in normal control animals. Motoneuron membrane electrical properties [axonal conduction velocity, afterhyperpolarization (AHP) half-decay time, rheobase, and input resistance] also returned to control levels in those motoneurons that made functional reconnection with the muscle (as determined by ability to elicit measurable tension). The relationships among motoneuron electrical properties were normal in motoneurons making functional reconnection. Approximately 10% of MG motoneurons sampled did not elicit muscle contraction. These cells' membrane electrical properties were different from those that did elicit muscle contraction. Contractile speed and fatigue resistance of reinnervated muscle units had recovered to control levels at 9 mo postoperation. Force generation did not recover fully in type-FF units. The reduced tensions were apparently due to failure of recovery of FG muscle fiber area. Following reinnervation, relationships between motoneuron electrical and muscle-unit contractile properties were similar to controls. This was reflected in a degree of correspondence between motor-unit type and motoneuron type similar to normal units (84 vs. 86%, as defined by Ref. 61). There was a significantly increased proportion of type-SO muscle fibers and a decrease in the fast muscle fibers (especially type FOG) in 9 mo reinnervated MG. Together with the unchanged proportions of motor-unit types, this led to an estimate of average innervation ratios being increased in type-S motor units and decreased in type-FR units.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Properties of self-reinnervated motor units of medial gastrocnemius of cat. I. Long-term reinnervation. 371 73

Motor units of the medial gastrocnemius (MG) and the single lateral gastrocnemius/soleus (LG/S) muscles of the opossum (Didelphis virginiana) were found to have uniformly slow contraction times relative to homologous muscles of the cat. Though a broad range of peak tetanic tensions was found among motor units from both muscles, most of the motor units were quite large relative to tension of the whole muscle. Comparison of the relative sizes of motor units showed that those of LG/S are significantly larger and slower than the units of MG. This suggests that the motor units of the two muscles may be differentially recruited during different behaviors. All of the MG and LG/S motor units were highly or moderately resistant to fatigue. Histochemical staining for NADH-diaphorase activity indicated consistently high levels of the enzyme in all of the fibers of both muscles. Apparently, all of the fast motor units consist of fast oxidative/glycolytic (FOG)-type muscle fibers. Our data provide functional evidence that the types of myofibrillar ATPase demonstrated by Brooke and Kaiser ('70), are not necessarily correlated to physiological classification of fiber types as slow oxidative (SO), fast oxidative/glycolytic (FOG), and fast glycolytic (FG) (Peter et al., '72). Perhaps compartmentalization of muscle fiber types may be a first step in the separation of muscles into multiple heads during the evolution of specialization to diverse locomotor habits among the mammals.
 ...
PMID:Motor units of the primary ankle extensor muscles of the opossum (Didelphis virginiana): functional properties and fiber types. 648 10

1. This report describes selected histochemical and physiological properties of the motor units of adult cat soleus muscle approximately one year after self- and cross-reinnervation with the nerve of the heterogenous flexor hallucis longus (f.h.l.). Self-reinnervated f.h.l. motor units are also considered. Whole muscles were tested for fibre reaction to alkaline pre-incubated ATPase, alpha-glycerophosphate dehydrogenase (alpha-GPD) and reduced nicotinamide adenine dinucleotide diaphorase (NADH-D). Motor units were isolated and studied by splitting the ventral root in acute preparations.2. The histochemical fibre type profile in the self-reinnervated muscle was comparable to normal muscle as was mean twitch contraction time, twitch-tetanus ratio and fatigue index. The mean tetanic tension of the soleus self- and cross-reinnervated motor units appeared close to a normal soleus whereas the mean tetanic tension of the f.h.l. self-reinnervated units was significantly less than a normal f.h.l.3. An average of 14% of the fibres of the soleus cross-reinnervated muscles had high ATPase and a alpha-GPD staining intensity in contrast to normal and self-reinnervated soleus in which such fibres are absent. Thus alkaline lability of myofibrillar ATPase increased in some fibres of what was originally a homogeneous population. The small increase in the number of densely staining fibres for ATPase at an alkaline pH (14%) was associated with a 73% decrease in (mean) contraction time (41 +/- 11 ms) of the thirty-three cross-reinnervated muscle units studied, with no unit's contraction time greater than 60 ms. Mean contraction times for the self-reinnervated soleus and f.h.l. muscles were 78 +/- 31 ms and 27 +/- 8 ms respectively.4. All fibres of the soleus cross-reinnervated muscles showed intense reaction to NADH-D, as was true of self-reinnervated soleus. This staining pattern is typical of normal soleus. In concordance, these motor units consistently demonstrated a high resistance to fatigue when stimulated for a four-minute period.5. These results suggest that in the adult self-and cross-reinnervated soleus muscle, there is some active mechanism which regulates the eventual size of motor units as reflected by tetanic tension.6. Change in contraction time from that typical for a soleus unit to that similar to an f.h.l. unit remains incomplete one year after cross-reinnervation. Within this time this partial change in single motor units reflects incomplete neural control of this property rather than a mixture of self- and foreign-innervation.7. A greater degree of independence from neural control to conversion of the histochemically demonstrated myofibrillar ATPase activity exists than is the case for contraction time.
 ...
PMID:Histochemical and physiological properties of cat motor units after self-and cross-reinnervation. 715 31

An N-acetylcysteine (NAC)/oltipraz (OLZ) combination was studied in healthy volunteer smokers who received daily NAC (1200 mg/day) and were randomized to weekly placebo (Arm A), OLZ 200 mg (Arm B), or 400 mg (Arm C). Treatment was for 12 weeks with follow-up at 16 weeks. The objective was to study toxicity and the modulation of pharmacodynamic end points. After treatment of 19 of a planned 60 subjects, (Arm A, six; Arm B, four; and Arm C, nine), the study was closed because of toxicity. Eight subjects failed to complete 12 weeks of drug administration, (Arm A, two, and Arm C, six). The most frequent side effects were gastrointestinal, fatigue, conjunctival irritation, and skin rash. Pharmacodynamic end points were measured pretreatment and 48 h after the dose of OLZ at weeks 1, 5, and 12 and 4 weeks after the end of treatment. Glutathione (GSH) was measured in plasma and in peripheral blood lymphocytes (PBLs). Other end points measured in PBLs were the enzyme activities of total glutathione-S-transferase (GST), GSTpi, and NAD(P)H:quinone oxidoreductase; and the mRNA expression of gamma-glutamylcysteine synthetase gammaGCS), GSTpi, and NAD(P)H:quinone oxidoreductase. GSH in PBLs, GST (total), and the mRNA of gammaGCS showed increases at some time points in some subjects. Most consistent was the mRNA of gammaGCS, which showed a > or = 30% increase at one or more time points in 11 of 19 subjects. Other end points were unchanged. We concluded that NAC/OLZ modulates some end points related to GSH but is too toxic for chemoprevention at the doses used.
 ...
PMID:Phase I/pharmacodynamic study of N-acetylcysteine/oltipraz in smokers: early termination due to excessive toxicity. 1130 98

The dithiolethione oltipraz is being developed as a chemopreventive agent for many malignancies, including colorectal cancer, on the basis of its in vivo protective activity against chemically induced tumors in a variety of animal models. This protection has been associated with an enhanced capacity to detoxify reactive carcinogens and, more recently, with increased DNA repair. In a previous single-dose study, elevated detoxification gene expression was observed in the days after oltipraz dosing. Now, in this clinical study, we evaluated the effects of oltipraz when given over a 3-month period. Fourteen individuals with increased risk for colorectal cancer were randomly assigned to one of two oral doses (125 or 250 mg/m2) of oltipraz twice weekly for 12 weeks. Two of seven subjects at the 250 mg/m2 dosage required dose reductions, owing to significant fatigue. The 125 mg/m2 dose level was well tolerated by all patients. Blood or colon tissue (or both) for evaluation of glutathione, glutathione S-transferase, DT-diaphorase activity, and DT-diaphorase mRNA expression were obtained prior to treatment and at weeks 6, 12, and 16. No significant modulation of phase II detoxification enzymes was seen at either dose studied during this period. Phase II trials evaluating a tolerable regimen of oltipraz (as demonstrated in this study) and other possible mechanisms that may be responsible for the protective activity of oltipraz should be pursued.
 ...
PMID:Chronic dosing of oltipraz in people at increased risk for colorectal cancer. 1153 Oct 12

The distribution of Fos-immunoreactive (Fos-ir) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-reactive neurons in the rat lumbar spinal cord was examined following muscle fatigue caused by intermittent high-rate (100 s(-1)) electrical stimulation of the triceps surae muscle or the ventral root L5 (VRL5) for 30 min. Following both types of stimulation, the fatigue-related c-fos gene expression was more extensive in the L2-L5 segments on the stimulated side, and the majority of Fos-ir neurons were concentrated in the dorsal horn. After direct muscle stimulation, the highest number of Fos-ir neurons were detected in two regions: layer 5, and superficial layers (1 and 2(o)), although many labeled cells were also found in layers 3, 4, 6, and 7. In response to VRL5 stimulation, the maximal density of Fos-ir neurons was detected in the middle and lateral parts of layers 1 and 2(o), the zone of termination of high-threshold muscle afferents(.) Statistically significant prevalence of Fos-ir cell number was also found in layers 5 and 7 on the stimulated side. A few Fos-ir neurons were detected in the ventral horn (layer 8 and area 10) on both sides. The lamellar distribution of NADPH-d-reactive neurons was similar over all experimental groups of animals. In the L3-L6 segments, such reactive cells were arranged in two distinct regions: dorsal horn (layers 2(i), 3, and 5) and area 10; in the L1 and L2 segments, an additional cluster of NADPH-d positive cells was found in the intermediolateral cell column (IML). Double-labeled cells were not detected. We suggest that c-fos expression in response to muscle fatigue reveals activity of functionally different types of spinal neurons which could operate together with NOS-containing cells in pre-motoneuronal networks to modulate the motoneuron output.
 ...
PMID:c-fos Expression and NADPH-d reactivity in spinal neurons after fatiguing stimulation of hindlimb muscles in the rat. 1174 76

Jian-pi-bu-xue-formula (JPBXF), a TCM formula composed of twelve Chinese medicinal herbs, has been used in clinic to ease patients' state of weakness and fatigue especially after receiving anti-tumor chemotherapy in China. The lack of the phytochemical characterization, detail therapeutic evaluation and mechanism of JPBXF remains the main limitation for its spreading. In this study, we systematically evaluated the effectiveness and underline mechanism of JPBXF on cyclophosphamide (CTX)-induced myelosuppression and identified the main constituents of JPBXF aqueous extract. JPBXF treatments reversed CTX-induced myelosuppression through increasing the number of haematopoietic stem cells (HSCs) and expression of C-kit in bone marrow cells. Simultaneously, JPBXF treatments alleviated CTX-induced blood cells reduction by increasing numbers of RBCs and WBCs and levels of GM-CSF, TPO and EPO in plasma. JPBXF treatments reduced CTX-induced immunosuppression by increasing expressions of CD3, CD4, and CD8a in PBMCs, and recovering structure damages of thymus and spleen. Moreover, JPBXF notably increased the expression of NRF2 compared with CTX group, and subsequently up-regulated HO1 and NQO1 both in mRNA and protein levels. In addition, eighteen compounds were recognized from JPBXF aqueous extract and the potential targets of the identified compounds were predicted. Overall, JPBXF can greatly reverse CTX-induced myelosuppression in C57BL/6 mice, especially in improving the blood and immune function through activating NRF2/HO1/NQO1 signaling pathway, which provides a reliable reference for JPBXF application in clinical. By recognizing eighteen compounds in JPBXF aqueous extract and predicting the underline mechanisms of the identified compounds, our study would provide theoretical guidance for further research of JPBXF.
 ...
PMID:Jian-Pi-Bu-Xue-Formula Alleviates Cyclophosphamide-Induced Myelosuppression via Up-Regulating NRF2/HO1/NQO1 Signaling. 3298 32