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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic potency of des-(B26-B30)-insulin-B25-amide, [TyrB25]des- (B26-B30)-insulin-B25-amide and [HisB25]des-(B26-B30)-insulin-B25-amide was studied in anaesthetized rats. Compared to insulin, full potency for des-(B26-B30)-insulin-B25-amide and an enhanced potency for both substituted analogues has been described previously on rat adipocytes in vitro. Hypoglycaemic effects following i.v. injection of all of these analogues were almost identical to those of native insulin with a half-maximal effective dose of approximately 3 nmol.kg-1. Stimulation of glucose metabolism during euglycaemic hyperinsulin-/analogueaemic clamp studies was indistinguishable from that of the native hormone with a maximal stimulation of approximately 19 mg.kg-1.min-1 and half-maximal effective hormone concentrations of approximately 1 pmol.ml-1. Analogue action on individual peripheral tissues estimated by the uptake of 2-deoxyglucose as well as stimulation of lipogenesis in epididymal fat was not different to that of insulin. These data demonstrate that C-terminal amidation of des-(B26-B30)-insulin results in a shortened molecule with full in vivo metabolic potency. When substituting phenylalanine in position B25 by tyrosine or histidine, the insulin-identical potency is preserved.
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PMID:In vivo metabolic activity of des-(B26-B30)-insulin-B25-amide and related analogues in the rat. 222 26

Hamster epididymal spermatozoa became virtually immotile following washing and dilution in chemically defined medium (TLP-PVA). The sperm motility factors (penicillamine, hypotaurine, and epinephrine: PHE) were examined for their ability to reactivate immotile sperm. Sperm could be reactivated by addition of PHE at 1 h of incubation. Hypotaurine alone was capable of reactivating sperm motility, but epinephrine and penicillamine together were not. However, overall sperm motility and percentage of motile sperm during incubation were higher when PHE components were used in combination than when hypotaurine was used alone. Addition of hypotaurine to immotile sperm suspensions could be postponed for up to 6 h with subsequent recovery of sperm motility, although the degree of recovery of motility declined progressively with each hour that addition of hypotaurine was delayed. The rescuing effect of hypotaurine was due to an increase both in the percentage of motile sperm and in the quality (grade) of sperm motility. The data show that hypotaurine is required for expression of sperm motility in the hamster, and support the concept that the loss of hypotaurine from sperm following washing and dilution is responsible for the sperm-immobilizing effect of these procedures. Additionally, the data demonstrate that hamster sperm can remain viable for several hours after becoming immotile, and that many of the immotile sperm are capable of being reactivated.
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PMID:Addition of hypotaurine can reactivate immotile golden hamster spermatozoa. 231 1

By using a chemically defined (protein-free) culture medium that supports sperm viability but not capacitation or the acrosome reaction, we have determined that hamster spermatozoa can be chemically capacitated in vitro by the divalent cation chelators D-penicillamine, L-histidine, and L-cysteine in the absence of bovine serum albumin (BSA). Washed cauda epididymal spermatozoa were preincubated (1-2 x 10(6) sperm/ml) for 3, 4, or 6 hr at 37 degrees C in 5% CO2 in air. The basic culture medium used for sperm preincubation and for sperm:egg coincubation was a modified Tyrode's solution (protein-free) containing 10 mM sodium lactate, 100 microM sodium pyruvate, and 1.0 mg/ml polyvinylalcohol (TLP-PVA). Sperm viability was maintained in all preincubation and coincubation media with PHE (20 microM D-penicillamine, 100 microM hypotaurine, and 1.0 microM epinephrine). The low control sperm preincubation medium consisted of TLP-PVA. In some cases the high control preincubation medium also contained 3 mg/ml BSA (TALP-PVA). The experimental preincubation medium was TLP-PVA with additional D-penicillamine (125 or 500 microM), or L-histidine (10, 100, or 1,000 microM) or L-cysteine (25, 75, or 125 microM). After preincubation, sperm were coincubated (2 x 10(4) sperm/ml) with cumulus-free hamster eggs in TALP-PVA +/- additional D-penicillamine, L-histidine, or L-cysteine for 1.5 hr, fixed, and evaluated for percent egg penetration as an index of sperm capacitation. The results demonstrate that hamster spermatozoa can be chemically capacitated in vitro with D-penicillamine (500 microM: range of mean penetration values, 53.6%-84.3%), L-histidine (100 microM: range of mean values, 24.8%-56.3%) or L-cysteine (75 microM: 51.3%) in the absence of exogenous protein.
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PMID:Capacitation of hamster spermatozoa with the divalent cation chelators D-penicillamine, L-histidine, and L-cysteine in a protein-free culture medium. 273 1

Cauda epididymal hamster spermatozoa were capacitated with D-penicillamine in a chemically defined (protein-free) medium (= "chemical" capacitation). Hamster zonae pellucidae were incapable of inducing functional acrosome reactions in chemically capacitated hamster sperm in a protein-free medium during sperm-egg coincubation. The culture medium used throughout incubation was a modified Tyrode's solution containing 10 mM sodium lactate, 100 microM sodium pyruvate and 1.0 mg/ml polyvinylalcohol (TLP-PVA). Sperm motility was maintained in all media with PHE (20 microM penicillamine, 100 microM hypotaurine, and 1.0 microM epinephrine). Additional D-penicillamine (125 or 500 microM) or 3 mg/ml bovine serum albumin (high control: TALP-PVA) was used to capacitate sperm during preincubation at 1-2 X 10(6) sperm/ml for 4.0 h at 37 degrees C in 5% CO2 in air. Sperm were then coincubated (2 X 10(4) sperm/ml) with cumulus-free hamster eggs in TALP-PVA or TLP-PVA +/- additional D-penicillamine (total: 500 or 125 microM) for 1.5 or 6.0 h. Percent egg penetration was used as the definitive index of sperm capacitation and functional acrosome reactions. Chemically capacitated sperm did not penetrate eggs (0.0 +/- 0.0%) in the absence of albumin during 1.5 h of sperm-egg coincubation. When sperm were chemically capacitated with 125 microM or 500 microM D-penicillamine, then coincubated with eggs for 6.0 h in the absence of albumin, only 18.8 +/- 28.6% and 23.7 +/- 29.7%, respectively, of eggs were penetrated. Significantly (p less than 0.05) more eggs (67.7 +/- 22.4%) were penetrated when coincubated with chemically capacitated sperm for 1.5 h in medium containing albumin. These results demonstrate that zonae pellucidae of hamster eggs require the presence of albumin to efficiently induce functional acrosome reactions in sperm that are chemically capacitated with D-penicillamine.
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PMID:Hamster zonae pellucidae cannot induce physiological acrosome reactions in chemically capacitated hamster spermatozoa in the absence of albumin. 280 2

Guinea pig spermatozoa were found to contain a fully-latent cysteine proteinase that could be unmasked by incubating epididymal sperm for 2 hr at pH 3.5 and 37 degrees C. The proteinase was identified as cathepsin L (EC 3.4.22.15) on the basis of its optimal hydrolysis of benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide (Z-Phe-Arg-NMec) at pH 5.5; lack of action on Z-Arg-Arg-NMec and Arg-NMec; urea-enhanced digestion of azocasein; marked sensitivity to thiol reagents, leupeptin, Z-Phe-Phe-CHN2, and L-trans-epoxy-succinylleucylamido(3-methyl)butane (Ep-475 or E-64-c); and insensitivity to pepstatin and serine proteinase inhibitors. Gossypol, a male antifertility agent, was inhibitory. The unmasking phenomenon was reversibly inhibited by HgCl2 and mersalyl acid, and prevented by leupeptin and Ep-475, but not by pepstatin.
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PMID:Cathepsin L--a latent proteinase in guinea pig sperm. 334 13

Protein synthesis and degradation were measured simultaneously in epididymal fat pads of rats by use of the incorporation of [14C]phenylalanine into protein and the sum of net protein breakdown and protein synthesis, respectively. Neither glucose nor insulin altered protein synthesis, but together they promoted this process; pyruvate could be substituted for glucose. Separately, glucose or insulin diminished proteolysis, and these effects were additive. In the presence of glucose and insulin, leucine, alanine, glutamine, glutamate, and aspartate lowered protein degradation to varying degrees but did not alter protein synthesis. Glutamate, but not leucine or alanine, was inhibitory without glucose and insulin present. When aminooxyacetic acid was provided to decrease the rate of transamination of amino acids, the inhibitory effects of leucine, alanine, and aspartate, but not of glutamate, appeared to be diminished. alpha-Ketoglutarate, but neither alpha-ketoisocaproate nor pyruvate, could diminish proteolysis. Inhibition of proteolysis was associated with a higher tissue content of glutamate and a greater production of glutamate and glutamine. These results suggest that glutamate itself may inhibit proteolysis in adipose tissue and mediate, at least in part, the effects of other amino acids.
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PMID:Regulation of protein turnover by glucose, insulin, and amino acids in adipose tissue. 614 13

Semisynthetic analogues of insulin were prepared from derivatives of desoctapeptide-(B23-30)-insulin (DOI). A1, B1-(Boc)2-DOI (di-Boc-DOI) was converted to A1, B1-(Boc)2-DOI-B22-phenylhydrazide (di-Boc-DOI-NHNH-C6H5) by the trypsin-catalyzed addition of phenylhydrazine in aqueous organic solvents at pH 6.5 [Canova-Davis, E., & Carpenter, F. H. (1981) Biochemistry 20, 7053-7058]. Treatment of di-Boc-DOI-NHNH-C6H5 with BNPS-skatole produced the phenyldiimide. The latter was coupled with a variety of protected peptides that, after removal of protecting groups, yielded the following compounds whose biological activities were compared to that of insulin in binding, in stimulation of hexose transport (), and in the stimulation of lipogenesis [)), in terms of percent of insulin activity, all in the isolated epididymal fat cell: di-Boc-DOI 0.2, (0.1), [0.2]; di-Boc-DOI-NHNH-C6H5 0.5, (0.2), [0.5]; DOI 0.2, (0.2), [0.1]; DOI-(Gly)B23 0.2, (0.2), [0.1]; DOI-(Gly-Phe)B23-24 6.3, (6.3), [8.0]; DOI-(Gly-Phe-Phe)B23-25 17.0, (25.6), [24.7]; DOI-(Gly-Phe-Phe-Tyr)B23-26 59.0, (50.0), [69.0]. The semisynthetic derivatives represent a stepwise readdition of the aromatic residues near the C terminus of the B chain. A given analogue demonstrated comparable activity in all three biological assays. The results indicate that the stepwise addition of aromatic residues to the B-chain C terminus of DOI produces an increase in insulin-like activity. The biological activity of DOI-(Gly-Phe-Phe-Tyr)B23-26, the derivative in which the aromatic region has been completely reassembled, is the same order of magnitude as that of insulin.
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PMID:Preparation of semisynthetic insulin analogues from bis(tert-butyloxycarbonyl)-desoctapeptide-insulin phenylhydrazide: importance of the aromatic region B24-B26. 634 Jul 39

Rabbit sperm pyruvate kinase remains bound to the cell structure of hypotonically treated mature rabbit epididymal spermatozoa (HTRES). It displays kinetic behavior very similar to that of rabbit muscle pyruvate kinase with regard to KM values for substrates, activation by monovalent and divalent cations, inhibition by phenylalanine which is reversed by alanine, and lack of activation by fructose-1,6-biphosphate. The flagellar ATPase also remains bound to the cell structure of HTRES, whose motility may be reactivated by a source of ATP. It requires Mg+2 for activity; the KM for both ATP and MG+2 is 0.2 mM, implying that MgATP is the substrate. The ATPase activity is not inhibited by ouabain, oligomycin, or vanadate, which also do not affect reconstituted motility, and is not affected by cyclic AMP in the presence of an inhibitor of phosphodiesterase. The activities of pyruvate kinase and the flagellar ATPase in a given preparation of HTRES are comparable. Rabbit spermatozoa have a metabolic strategy which is very similar to muscle cells. This suggests that the major use of the sperm cell's metabolic machinery is maintenance of energy for the contractile work of motility and that only minor amounts of metabolic energy appear to be consumed in other reactions, including those involved in fertilization.
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PMID:Properties of pyruvate kinase and flagellar ATPase in rabbit spermatozoa: relation to metabolic strategy of the sperm cell. 644 94

Three factors were studied for their effects on the first cleavage division of in vitro fertilized hamster eggs. Eggs from superovulated females were inseminated with precapacitated epididymal hamster sperm in medium containing either fatty acid-free (FAF) or fraction V (V) bovine serum albumin (BSA), in the presence or absence of cumulus cells. After incubation for 3 to 4 h with sperm, eggs were transferred to culture medium containing FAF- or V-BSA, with or without amino acids (glutamine, isoleucine, methionine, and phenylalanine), and the percentages of eggs cleaving to two cells were recorded after a further 20 h of incubation. Fatty acid-free BSA was found to support a significantly higher percentage of eggs cleaving than V-BSA and was used in all further experiments. The presence of cumulus cells during fertilization was found to have a beneficial effect on cleavage when no amino acids were added to the culture medium, but when amino acids were included, eggs fertilized with or without cumulus present cleaved equally well. These results represent another step toward defining the optimal environmental conditions for obtaining the first cleavage division of hamster eggs in vitro.
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PMID:The effects of amino acids, cumulus cells, and bovine serum albumin on in vitro fertilization and first cleavage of hamster eggs. 668 53

An analogue of porcine insulin which differs from the native molecule in that the tyrosine residue in Pos. A19 is replaced by phenylalanine has been synthesized. The [PheA19]A chain was synthesized by the fragment condensation and purified as tetra-S-sulfonate by ion-exchange chromatography on DEAE-cellulose at pH 3.5. Conversion of the latter into the sulfhydryl form and combination with native sulfhydryl B chain yielded the [PheA19]insulin, which was purified by ion-exchange chromatography on CM-cellulose at pH 4.0 with an linear NaCl gradient. The biological activity of this analogue was 22.6% as measured by the rat epididymal adipocytes. It was suggested that in the insulin molecule the hydroxyl function of A19-tyrosine participates in an hydrogen-bond with the carbonyl function of A1-glycine. That hydrogen bond formation is critical for the stability of the hormone-receptor complex. The low biological activity found by us supports this hypothesis. The circular dichroism data in far UV suggest that the introduction of phenylalanine leaves the molecule structure essentially undisturbed, however the change observed in near UV could be accounted for the exchange.
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PMID:(A1-phenylalanine) insulin: a new synthetic analogue. 700 Jun 56


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