Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.
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PMID:Models of insulin action on metabolic and growth response genes. 162 85

Stromal vascular cells were isolated from adipose tissue obtained from three different anatomical locations: epididymal (EPI), retroperitoneal (RP), and dorsal subcutaneous (SC), and allowed to differentiate in primary tissue culture. Cell number, protein concentration, glycerophosphate dehydrogenase, and lipoprotein lipase activity were similar in cells obtained from the EPI, RP, and SC regions, as were total insulin binding and the affinity of insulin for its receptor. However, both maximal insulin receptor tyrosine kinase activity and insulin-stimulated phosphorylation of the insulin receptor were significantly lower (P less than 0.05) in cells cultured from the SC region. In addition, newly differentiated adipocytes from the SC region were less sensitive to the ability of insulin to stimulate glucose uptake, and maximal insulin-stimulated glucose uptake by these cells was also significantly lower (P less than 0.05) when compared to cells obtained from the two other regions. Since these studies were performed on adipocyte precursor cells, allowed to differentiate to a similar degree in primary culture, the observed differences in insulin receptor phosphorylating activity, as well as the ability of insulin to stimulate glucose uptake appear to be intrinsic to adipose tissue from the three sites.
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PMID:Differences in insulin action as a function of original anatomical site of newly differentiated adipocytes obtained in primary culture. 165 46

Treatment of bull spermatozoa from epididymal cauda with 5 micrograms digitonin per microliter cells removed the permeability barrier of plasma membrane for mitochondrial substrates and effectors. Such preparations yielded a high portion of coupled mitochondria characterized by ratios of active respiration to carboxyatractyloside-inhibited respiration greater than 13 in the presence of efficient substrates. Bull sperm mitochondria oxidized pyruvate and lactate in the presence of malate as well as glycerol-3-phosphate with much higher rates than succinate or palmitoyl carnitine. For the efficient substrates the respiration coupled to ADP phosphorylation amounted to 77 to 100% of the uncoupled rate. Comparable rates of active respiration were also observed with ATP indicating the high ATPase activity present in digitonin-treated spermatozoa. Uncoupled rates of respiration corresponded to rates of intact spermatozoa, but the capacity of the phosphorylating respiration exceeded the respiration rates of intact motile spermatozoa remarkably. This indicates that the spermatozoal ATP turnover at sufficient supply of substrate is mostly controlled by ATP utilizing reactions.
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PMID:Capacities of oxidative metabolism in digitonin-treated bovine epididymal spermatozoa. 356 16

Goat cauda-epididymal intact spermatozoa have been shown to possess an ecto-cyclic AMP-independent protein kinase activity on the external surface that causes phosphorylation of the serine and threonine residues of exogenous phosvitin. The enzyme is neither a tyrosine kinase nor a catalytic subunit of the cyclic AMP-dependent protein kinase. It is not activated by Ca2+, calmodulin and phosphatidylserine. The intact-cell enzyme is capable of phosphorylating a variety of proteins including sperm plasma membrane-bound phosphoprotein(s). The enzymic activity of the intact spermatozoa was not due to contamination of broken or "leaky" cells. The kinase activity of the whole cells was strongly inhibited by the non-penetrating surface probes: p-chloromercuriphenylsulphonic acid (10 microM) and proteases (125 micrograms/ml). The specific activity of the ecto-kinase increased nearly 100% during vigorous forward progression of spermatozoa.
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PMID:An ecto-cyclic AMP-independent protein kinase in goat spermatozoa and its change of activity during forward motility. 381 58

Tyrphostins inhibit tyrosine kinases and have little effect on the activity of serine/threonine kinases. Pyruvate dehydrogenase kinase inactivates pyruvate dehydrogenase by phosphorylating serine residues within the multienzyme complex. This serine/theronine kinase represents a new family of protein kinases, and one (tyrphostin 47) of two tyrphostins tested appeared to activate the pyruvate dehydrogenase kinase as determined by [1-14C]-lactate oxidation to 14CO2. Experiments designed to determine if the tyrphostins altered pyruvate dehydrogenase activity in mitochondria prepared from rat epididymal adipocytes using [1-14C]-pyruvate as the substrate demonstrated a dose dependent increase in enzyme activity in the presence of tyrphostin 47, but not in tyrphostin 23. This apparent stimulation of pyruvate dehydrogenase activity was attributed to tyrphostin 47's ability to nonenzymatically decarboxylate [1-14C]-pyruvate, the substrate for the pyruvate dehydrogenase assay. Neither tyrphostin directly altered pyruvate dehydrogenase kinase activity. Therefore, assays utilizing [1-14C]-pyruvate and tyrphostin 47 are subject to analytical interference.
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PMID:Tyrphostin 47 nonenzymatically decarboxylates [1-14C]-pyruvate. 781 37

Cultured rat epididymal tissue explants formed >90% pure, adherent growing epithelial cell monolayers. Despite their flattened and apparently androgen receptor-negative phenotype, these cells for a short period kept characteristics of the epididymal duct epithelium, i.e., expression of the tissue-specific marker CD52 and responsiveness of its mRNA toward temperature elevation and androgen withdrawal. When cells were grown on permeable supports at 33 degrees C, androgen supplementation or withdrawal specifically modulated the levels as well as the length of the CD52 mRNA. Elevation of the culture temperature to a quasi abdominal milieu of 37 degrees C selectively reduced the CD52 mRNA levels under all culture conditions. This reduction was not affected by the presence of androgens and was not accompanied by changes in length, suggesting that the modulation of CD52 mRNA in epididymal cells by androgens and by temperature is synergic, but may involve different molecular mechanisms. CD52 mRNA levels, however, were not stable in the primary cultures but decreased rapidly to undetectable levels after 4-5 days at all culture conditions. GAPDH mRNA levels, on the other hand, were stable throughout the culture period.
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PMID:CD52 mRNA is modulated by androgens and temperature in epididymal cell cultures. 1073 64

As mammalian spermatozoa migrate through the epididymis, they acquire functionality characterized by the potential to express coordinated movement and the competence to undergo capacitation. The mechanisms by which spermatozoa gain the ability to capacitate during epididymal transit are poorly understood. The purpose of this study was to investigate the impact of epididymal maturation on the signal transduction pathways regulating tyrosine phosphorylation, because this process is thought to be central to the attainment of a capacitated state and expression of hyperactivated motility. Western blot and immunocytochemical analyses demonstrated that epididymal maturation in vivo is associated with a progressive loss of phosphotyrosine residues from the sperm head. As cells pass from the caput to the cauda epididymis, tyrosine phosphorylation becomes confined to a narrow band at the posterior margin of the acrosomal vesicle. Epididymal maturation of rat spermatozoa was also associated with an acquired competence to respond to high levels of intracellular cAMP by phosphorylating tyrosine residues on the sperm tail. Immature caput spermatozoa were incapable of exhibiting this response, despite the apparent availability of cAMP and protein kinase A. These findings help to clarify the biochemical changes associated with the functional maturation of spermatozoa during epididymal transit.
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PMID:Impact of epididymal maturation on the tyrosine phosphorylation patterns exhibited by rat spermatozoa. 1131 63

As spermatozoa mature within the epididymis they acquire the potential for capacitation and ultimately fertilization. In biochemical terms, the former is reflected in the progressive activation of a signal transduction pathway characterized by cAMP-mediated induction of phosphotyrosine expression on the sperm tail. In this study, we have examined the cellular mechanisms controlling this maturational event. Caput epididymal spermatozoa exhibited tyrosine phosphorylation on the sperm head that was largely unresponsive to cAMP and not significantly impaired by removal of extracellular HCO(3) (-). In contrast, caudal epididymal spermatozoa exhibited low levels of phosphorylation on the sperm head, yet responded dramatically to cAMP by phosphorylating a new set of proteins on the sperm tail via mechanisms that were highly dependent on extracellular HCO(3) (-). The impact of extracellular HCO(3) (-) depletion on caudal cells was not associated with a significant change in the redox regulation of cAMP but could be fully reversed by buffering the intracellular pH with N-Tris[Hydroxymethyl]methyl-3-amino-propanesulfonic acid (TAPS). The pattern of tyrosine phosphorylation was also profoundly influenced by the presence or absence of added extracellular calcium. In the presence of this cation, only caudal spermatozoa could respond to increased extracellular cAMP with tyrosine phosphorylation of the sperm tail. However, in calcium-depleted medium, this difference completely disappeared. Under these conditions, caput and caudal spermatozoa were equally competent to exhibit phosphotyrosine expression on the sperm tail in response to cAMP. These results emphasize the pivotal role played by calcium and HCO(3) (-) in modulating the changes in tyrosine phosphorylation observed during epididymal maturation.
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PMID:Development of the signalling pathways associated with sperm capacitation during epididymal maturation. 1258 57