Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence for immunologic processes taking part in the pathogenesis of what until now has been called the "essential" form of EPH gestosis is cited. The name of immunogestosis (IG) is introduced. The data of this preliminary study suggest that regular "inoculation" of the female genital tract with allogeneic spermatozoal histocompatibility antigens reduces the incidence of IG. Information about preconceptional sexual habits and contraceptive measures was obtained from 83 selected primigravid patients. Twenty-eight women had mild to moderate IG (Group B);55 did not (Group A). Women in Group B had had less contact with spermatozoa of partners than did women in Group A. Oral contraceptive consumption was less in Group B than in Group A. Women in Group B were younger than women in Group A. All these differences were statistically significant. A new immunoetiologic hypothesis referring to IG, as well as the theoretic and clinical implications arising from it, are discussed. This hypothesis is based on the assumption that spermatozoal histocompatibility antigens can either induce immunologic tolerance or be responsible for the phenomenon of immunologic enhancement in the maternal immunosystem. As the fetus inherits paternal histocompatibility antigens, it is concluded that pre-existing tolerance (or enhancement) exerts an IG-preventive function in a subsequent pregnancy.
...
PMID:Immunogestosis: a new etiologic concept of "essential" EPH gestosis, with special consideration of the primigravid patient; preliminary report of a clinical study. 87 7

Reported similarities in the acute toxic effects of 1,2-dibromo-3-chloropropane (DBCP), 3-chloro-1,2-propaneoxide (epichlorohydrin, ECH), 3-chloro-1,2-propanediol (alphachlorohydrin, ACH), and oxalic acid (OA) have been suggested as presumptive evidence that the metabolism of DBCP to OA, via ECH and ACH, is the cause of the resulting injuries to the kidney and, perhaps, to the epididymis and testis. To test this hypothesis, the comparative toxicities of these four chemicals were studied in male rats after single subcutaneous (sc) injections of maximally tolerated (nonlethal) doses. Kidney, testicular, and liver functions were monitored, and the occurrences of morphological changes in these and several other organs were evaluated 24 hr, 3, 8, 25, and 75 days post-treatment. DBCP caused renal dysfunction (alterations in urine composition and reduced glomerular filtration rate) and marked necrosis of the proximal tubular epithelium in the outer medulla of the kidney. ACH and OA also elicited renal dysfunction, but ACH produced only a mild swelling of the proximal tubular epithelium in the renal cortex and OA produced a focal necrosis anatomically associated with crystal deposition. ECH caused a swelling of the proximal tubular epithelium in the renal cortex, but not frank kidney dysfunction. DBCP also caused a reversible vacuolization of the tubular epithelium in the caput epididymis, progressive testicular atrophy, and a reduction of cauda epididymal sperm concentration. ACH and ECH produced similar effects, as well as epididymal sperm granulomas, spermatocoeles, and an increase in the number of morphologically abnormal spermatozoa. OA failed to produce discernible epididymal or testicular lesions at any time during the study. The development of similar lesions in the epididymis and testis following DBCP, ECH, or ACH treatments is consistent with the theory of metabolism of these chemicals to a common causative gonadotoxic agent. Oxalic acid (OA), however, would not appear to be the common gonadal toxicant. Differences in the effects, both morphological and functional, of DBCP, ECH, ACH, and OA on the kidney, moreover, indicate that DBCP nephropathy is not mediated through metabolism to OA and suggest, as well, that it differs causally from that induced by ECH or ACH. Therefore, the metabolism of DBCP to ECH or ACH, and of ECH or ACH to OA, is insufficient to explain totally the toxic effects of these agents on the urogenital system in male rats.
...
PMID:The comparative effects of 1,2-dibromo-3-chloropropane (DBCP) and its metabolites, 3-chloro-1,2-propaneoxide (epichlorohydrin), 3-chloro-1,2-propanediol (alphachlorohydrin), and oxalic acid, on the urogenital system of male rats. 661 40

The c-KIT proto-oncogene encodes for a transmembrane receptor and is associated with maturation of several cell types, including germ cells. The ligand of the receptor has been identified as stem cell factor (SCF). Loss or alteration of the expression of either of these factors leads to anemia, albinism, and/or sterility in mice. We examined the expression of c-KIT and SCF by immunohistochemistry in specimens from normal and infertile human testis. All specimens were obtained in the evaluation of male subfertility. We were able to demonstrate staining for c-KIT in Leydig cells in all specimens. Normal testis stained for c-KIT in the cytoplasm of early spermatogenic cells, as well as the acrosomal granules of the round spermatids and the acrosome of testicular spermatozoa. However, staining in testis demonstrating maturation arrest failed to demonstrate acrosomal staining, and Sertoli-only specimens demonstrated staining for c-KIT in Leydig cells only. The results for SCF demonstrated an overall uniform staining of Leydig cells in all specimens. The intensity of staining of Sertoli cells increased from normal to maturation arrest to Sertoli-only specimens. Germ cell staining was consistently negative. We hypothesize that these staining patterns for SCF are due to either lack of staining of the receptor-ligand complex or overexpression of the kit ligand in tissue that does not express the kit receptor. It appears that the c-kit receptor is expressed in the acrosome of developing germ cells, as well as in Leydig cells and early spermatogenic cells, suggesting a role in the acrosome reaction, as well as germ cell maturation and differentiation.
...
PMID:Expression of c-KIT and its ligand, stem cell factor, in normal and subfertile human testicular tissue. 888 3

The presence of mRNAs in human ejaculate spermatozoa is well established, yet little is known of the representation or function of these transcripts. To address these issues, the complexity of spermatozoal RNA was examined. As expected, testis-expressed mRNAs were detected by RT-PCR in mature human spermatozoa. Interestingly, when a testis cDNA library was probed with total spermatozoal RNA, less than 2% of plaques gave a strong hybridization signal, suggesting a rather unique sperm-derived population. To further define the sequence distribution, 18 strongly hybridizing clones were selected at random for end-sequence analysis. Twelve matched unique sequences in the EST, STS and NR databases, whereas five showed no similarity to any of the sequences in the databases. In addition, one clone belonged to the SINE repetitive element family. As demonstrated by sequencing randomly primed cloned inserts, short (SINE/MER) or long (LINE/ORF2) interspersed repeat-like sequences are also contained as part of the spermatozoal RNA fraction. It is now evident that human spermatozoa contain a rich repertoire of both known and unknown protein-encoding and non-coding RNAs. This provides a unique opportunity to identify and investigate the many genes responsible for the structure and function/dysfunction of the male gamete using spermatozoal RNA as the template.
...
PMID:A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis. 1052 62

Spermatozoal function is affected by the ability to regulate intracellular calcium concentrations ([Ca2+]i), and may be influenced by epididymal maturation as well as environmental components. Regulation of [Ca2+]i in ejaculated and epididymal stallion spermatozoa was monitored over time in various media. Spermatozoa from each of 5 pony stallions (3 ejaculate samples and 1 caput and cauda sample) were labeled with the fluorescent calcium indicator probe Indo-1 in a calcium-free modified Tyrode's buffer. Fluorescent emissions were monitored by a dual wavelength spectrofluorometer over 5 h. Calcium (1 mM) was added at T = 15 min, and heparin (HEP; 10 micrograms/ml) or heparin plus glucose (hGLUC; 5 mM in 10 micrograms/ml heparin) was added at T = 30 min. Spermatozoal Ca2+ content and regulation differed among males (P = 0.0066). Relative initial [Ca2+]i differed significantly among all stages of maturity (0.84 +/- 0.104, 0.76 +/- 0.023, 1.20 +/- 0.036 LSM of relative Ca2+ units for caput, cauda and ejaculate spermatozoa respectively; P = 0.001). Rate of Ca2+ uptake was similar for ejaculate and cauda spermatozoa (0.021 +/- 0.005 and 0.026 +/- 0.002 relative Ca2+ units/sec) but slower for caput spermatozoa (0.012 +/- 0.001; P = 0.0006). There was no immediate effect of HEP or hGLUC in any stage (P > 0.05), and caput spermatozoa did not differ from cauda spermatozoa for any treatment or time period. A significant increase in [Ca2+]i was seen in ejaculate spermatozoa treated with HEP from 2 h on (P < 0.05). This study demonstrates that both the absolute Ca2+ concentration and the rate of Ca2+ internalization in equine spermatozoa is dependent on the stage of maturation. Ejaculate spermatozoa respond to heparin through increased [Ca2+]i, which may play a role in the fertilizing ability of ejaculate spermatozoa.
...
PMID:Epididymal maturation affects calcium regulation in equine spermatozoa exposed to heparin and glucose. 1073 46

Pig oocytes at metaphase II were activated by penetration of spermatozoa in cycloheximide-free and cycloheximide-containing fertilisation media. The precise nuclear stage, and the kinetics of degradation of cyclin B1 and dephosphorylation of MAP kinase were assessed after insemination. After maturation culture, 96% of oocytes reached metaphase II. At 6 h after insemination in cycloheximide-free medium, 68% of the oocytes were activated and had progressed to anaphase II or beyond. After 8 h, 89% of the oocytes were activated: a female pronucleus had formed and the heads of penetrating spermatozoa had enlarged and changed to male pronuclei. In the cycloheximide-containing medium, activation of oocytes started earlier than in cycloheximide-free medium. After 4 h, 43% of the oocytes were activated, and the percentage increased to 97% after 6 h. Pig cyclin B1 disappeared in the oocytes at 6 h after insemination in both cycloheximide-containing and cycloheximide-free media. Pig oocytes at metaphase II contained two types of MAP kinase--ERK 1 and ERK 2--in their active phosphorylated forms. At 8 h after insemination ERK 2 changed to the fast-migrating inactive form in the oocytes cultured in both cycloheximide-containing and cycloheximide-free media, although the shift-down was not complete. The change was delayed by 2 h after the degradation of cyclin B1 molecules. These results demonstrate that degradation of pig cyclin B1 molecules corresponds to the transition of the oocytes from metaphase II arrest to anaphase II/telophase II and was followed by MAP kinase dephosphorylation.
...
PMID:Degradation of pig cyclin B1 molecules precedes MAP kinase dephosphorylation during fertilisation of the oocytes. 1085 86

Because poorly motile sperm samples can often be stimulated by treatments that increase intracellular levels of cyclic adenosine monophosphate (cAMP), it has been supposed that such samples are unable to maintain an adequate supply of the cyclic nucleotide with which to activate protein kinase A (PKA). To investigate this hypothesis, we incubated boar sperm samples with bicarbonate (a stimulator of adenylyl cyclase) and compared its effect with that of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3',5'-cyclic monophosphothioate (cBIMPS, a highly permeable and stable cAMP analog). Videomicroscopy assessment of motility was followed by computer analysis of the sperm tracks to produce motility descriptor values for many individual cells in each sample, whence "cluster" analysis of these data identified groups of spermatozoa that differed in motility characteristics. Bicarbonate stimulation of motility was characterized by an increase in the linearity (LIN) and progressive velocity of part of the sperm population only. The size of this "fast linear" subpopulation varied considerably between ejaculates. However, treatment with cBIMPS did not induce significantly more "fast linear" sperm than treatment with bicarbonate. In further experiments investigating the role of protein kinases in motility control, bicarbonate stimulation was greatly inhibited by H89 (a specific inhibitor of PKA), whereas GF109203X and lavendustin A (inhibitors of protein kinase C [PKC] and protein tyrosine kinase [PTK], respectively) had essentially no effect. While inclusion of the protein phosphatase inhibitor calyculin stimulated motility, it failed to increase the overall percentage of "fast linear sperm" induced by bicarbonate. We conclude that intersperm and interejaculate differences in boar sperm motility are not due to inadequacy in cAMP supply or to ineffective PKA activity.
...
PMID:Bicarbonate stimulation of boar sperm motility via a protein kinase A-dependent pathway: between-cell and between-ejaculate differences are not due to deficiencies in protein kinase A activation. 1206 64

Incubation of gradient purified human spermatozoa, which are routinely maintained in media prior to IVF and intracytoplasmic sperm injection (ICSI), induced DNA strand breaks (up to 89 nicks x 10(-3) bp) and chromatin release. Unlike highly dispersed Alu repeat sequences, the centromeric heterochromatin was much less susceptible to endonuclease attack. In addition to chromatin release, the permeability of the sperm membrane was altered as evidenced by reduced accessibility of sperm nuclei to decondensation factors in mouse embryo extracts. Hybridization of cDNA microarrays with DNA released from spermatozoa revealed a consistent hypersensitivity of certain genes to endogenous cleavage including TP53, VHL (tumour suppressors), BRCA1 (breast cancer), NOS1 (neurotransmitter), PECAM1, FLT1 (angiogenesis) and CDKN1C (cell cycle/imprinted). N-tert-butyl hydroxylamine (NTBH), a derivative of the anti-teratogenic alpha-phenyl-N-t-butyl nitrone (PBN) and synthetic superoxide dismutase (SOD)/catalase mimetics inhibited chromatin release and sustained or dissipated relative mitochondrial membrane potential. Together, these results show a link between the hyperactivation of sperm mitochondria and chromosomal damage of specific genes in vitro, and that the potential risk of disruption of paternally contributed genes can be circumvented by antioxidants which are known to target mitochondria.
...
PMID:Gene-specific chromatin damage in human spermatozoa can be blocked by antioxidants that target mitochondria. 1465 2

Acrosome reaction (AR) is an exocytotic process of fundamental importance for the spermatozoon to fertilize the oocyte. The mechanisms mediating this process are only partially defined. The aim of the present study was to investigate the role of various kinases and the extracellular signal-regulated kinase (ERK) pathway in the induction of the AR and associated phosphorylation of tyrosine (Tyr) residues and of the threonine-glutamic acid-tyrosine (Thr-Glu-Tyr) motif that occurs in 80 and 105 kDa proteins (p80/p105). Human spermatozoa were capacitated and AR was induced with lysophosphatidylcholine in the presence of inhibitors of various kinases and of the ERK pathway. Phosphorylation of Tyr and of Thr-Glu-Tyr peaked 15 min after the induction of the AR. Both phosphorylations were prevented by inhibitors of protein kinase C, MEK, phosphoinositide 3-kinase and Akt but not by protein kinase A inhibitors. Phosphorylation of Thr-Glu-Tyr, but not Tyr, was decreased by inhibitors of protein tyrosine kinase and Grb2-SH2. All the inhibitors prevented lysophosphatidylcholine-induced AR, indicating the involvement of PKC, PKA, PTK, PI3K, Akt and the ERK pathway. These results show that phosphorylation of Tyr and Thr-Glu-Tyr are associated with the AR and are differently regulated by the various kinases emphasing the complexity of this process.
...
PMID:Various protein kinases regulate human sperm acrosome reaction and the associated phosphorylation of Tyr residues and of the Thr-Glu-Tyr motif. 1570 55

Capacitation is an essential process by which spermatozoa acquire fertilizing ability. Reactive oxygen species (ROS), protein kinase A (PKA), protein kinase C (PKC), protein tyrosine kinases (PTKs), and the extracellular signal-regulated protein kinase (ERK or mitogen-activated protein kinase [MAPK]) pathway regulate sperm capacitation. Our aim was to evaluate the phosphorylation of MEK (MAPK kinase or MAP2K) or MEK-like proteins in human sperm capacitation and its modulation by ROS and kinases. Immunoblotting using an anti-phospho-MEK antibody indicated that the phosphorylation of three protein bands (55, 94, and 115 kDa) increased in spermatozoa treated with fetal cord serum ultrafiltrate (FCSu), BSA, or isobutylmethylxanthine plus dibutyryl cAMP as capacitating agents. These phospho-MEK-like proteins are localized along the sperm flagellum. The MEK-inhibitors PD98059 and U126 prevented this phosphorylation, suggesting that these proteins are MEK-like proteins. The ROS scavengers prevented, and the addition of H(2)O(2) or spermine-NONOate (nitric oxide donor) triggered, the increase of phospho-MEK-like proteins. The capacitation-related increases in phospho-MEK-like proteins induced by FCSu, H(2)O(2), and spermine-NONOate were similarly modulated by PKA, PKC, and PTK, suggesting ROS as mediators in this phenomenon. These results indicate that phospho-MEK-like proteins are modulated by ROS and kinases and probably represent an intermediary step between the early events and the late tyrosine phosphorylation associated with capacitation.
...
PMID:Reactive oxygen species and protein kinases modulate the level of phospho-MEK-like proteins during human sperm capacitation. 1577 58


1 2 3 4 5 6 7 Next >>

---