An epidemiological study of androgenic alopecia in 3114 Korean patients.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

Differential signaling of glial cell line-derived neurothrophic factor and brain-derived neurotrophic factor in cultured ventral mesencephalic neurons.

In the ventral mesencephalon, two neurotrophic factors, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, have been shown previously to have similar effects on the survival of dopaminergic neurons. Here, we compared the signaling mechanisms for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, focusing on the mitogen-associated protein kinase and the transcription factor cyclic-AMP responsive element-binding protein. Double-staining experiments indicated that many neurons co-expressed the receptors for glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor, c-RET and TrkB, suggesting that they are responsive to both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced a rapid phosphorylation of mitogen-associated protein kinase and cyclic-AMP, responsive element-binding protein, there were significant differences in the kinetics and pharmacology of the phosphorylation. The phosphorylation of mitogen-associated protein kinase by glial cell line-derived neurotrophic factor was transient; within 2 h, the level of mitogen-associated protein kinase phosphorylation returned to baseline. In contrast, the effect of brain-derived neurotrophic factor was long lasting; the mitogen-associated protein kinase remained phosphorylated for up to 4 h after brain-derived neurotrophic factor treatment. PD098059, a specific inhibitor for mitogen-associated protein kinase kinase, completely blocked the glial cell line-derived neurotrophic factor signaling through mitogen-associated protein kinase, but had no effect on brain-derived neurotrophic factor-induced mitogen-associated protein kinase phosphorylation. Both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor induced the phosphorylation of cyclic-AMP responsive element-binding protein in the nuclei of ventral mesencephalon neurons. However, PD098059 blocked the cyclic-AMP responsive element-binding protein phosphorylation induced by glial cell line-derived neurotrophic factor, but not that by brain-derived neurotrophic factor. These results indicate that, although both brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor act on ventral mesencephalon neurons, the two factors have different signaling mechanisms, which may mediate their distinctive biological functions.

Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice.

Brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using two lines of BDNF knockout mice. Among other presynaptic impairments, the mutant mice exhibited more pronounced synaptic fatigue at CA1 synapses during high-frequency stimulation, compared with wild-type animals. Quantitative analysis of CA1 synapses revealed a significant reduction in the number of vesicles docked at presynaptic active zones in the mutant mice. Synaptosomes prepared from the mutant hippocampus exhibited a marked decrease in the levels of synaptophysin as well as synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a protein known to be involved in vesicle docking and fusion. Treatment of the mutant slices with BDNF reversed the electrophysiological and biochemical deficits in the hippocampal synapses. Taken together, these results suggest a novel role for BDNF in the mobilization and/or docking of synaptic vesicles to presynaptic active zones.

Differential effects of GDNF and BDNF on cultured ventral mesencephalic neurons.

Previous studies have shown that brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) can enhance the survival of dopaminergic neurons in the ventral mesencephalon (VM). Here we compared several non-survival functions of the two factors in VM neurons in culture. We found that both BDNF and GDNF elicited an increase in the depolarization-induced release of dopamine, but had no effect on GABA release, in the VM cultures. BDNF, but not GDNF, significantly enhanced the expression of the calcium binding protein calbindin and synaptic protein SNAP25. In contrast, treatment of the cultures with GDNF, but not BDNF, elicited a marked fasciculation of the processes of the VM neurons. Thus, although both act on VM neurons, BDNF and GDNF have distinct functions.

Expression and complex formation of soluble N-ethyl-maleimide-sensitive factor attachment protein (SNAP) receptors in clonal rat endocrine cells.

Syntaxin, synaptosome-associated protein 25 (SNAP-25) and synaptobrevin are neuronal receptors of N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP), cytosolic proteins essential for membrane transport. The expression of these SNAP receptors was investigated by immunoblotting in clonal endocrine cells; catecholamine-secreting adrenal medullary cells (PC12), growth hormone-secreting pituitary cells (GH3), and insulin-secreting pancreatic beta-cells (RINr and RINm5F). All of these receptors as well as NSF and SNAP are expressed in these cells and, co-immunoprecipitation experiments indicate that syntaxin is associated with SNAP-25 and synaptobrevin after solubilization. These results suggest that syntaxin, SNAP-25, and synaptobrevin form a complex and are involved in the secretion of hormones from endocrine cells by exocytosis.

HPC-1 is associated with synaptotagmin and omega-conotoxin receptor.

Monoclonal antibodies were produced that recognize a membrane protein of 35,000 Da (p35) expressed in brain and adrenal medulla. They immunoprecipitated 50% of omega-conotoxin (omega-CgTX) receptor, a putative N-type calcium channel, solubilized from rat brain. Anti-synaptotagmin (p65) antibodies also immunoprecipitate omega-CgTX receptor (Leveque, C., Hoshino, T., David, P., Shoji-Kasai, Y., Leys, K., Omori, A., Lang, B., El Far, O., Sato, K., Martin-Moutot, N., Newsom-Davis, J., Takahashi, M., and Seagar, M.J. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 3625-3629); however, immunoprecipitation by anti-p35 antibodies and anti-synaptotagmin antibodies was not additive. Furthermore, both p35 and synaptotagmin were recovered in the immunoprecipitates with anti-synaptotagmin and anti-p35 antibodies, respectively, indicating that a population of omega-CgTX receptor exists as a ternary complex with synaptotagmin and p35. A cDNA coding p35 was isolated from a rat brain cDNA library by immuno-screening, and the primary structure of the protein was revealed to be identical to that of HPC-1 (Inoue, A., Obata, K., and Akagawa, K. (1992) J. Biol. Chem. 267, 10613-10619). HPC-1 has a putative transmembrane segment at the C terminus and four heptad motifs, which may be involved in protein-protein interaction. These results suggest that HPC-1 may play a role in neurotransmitter release from nerve terminals by associating with omega-CgTX-sensitive N-type calcium channel and synaptotagmin.

Interaction of the low-molecular-mass, guanine-nucleotide-binding protein with the actin-binding protein and its modulation by the cAMP-dependent protein kinase in bovine platelets.

Platelets have been shown to possess several, different, low-molecular-mass, guanine-nucleotide-binding proteins (G-proteins) with molecular masses about 20-30 kDa. We report here that a 25-kDa G-protein copurified with the bovine platelet actin-binding protein (ABP), a cross-linker of actin filaments which is known to generate the three-dimensional network of actin. Both the G-protein and ABP were recovered in a fraction that was insoluble in Triton X-100 and were extracted in 0.6 M NaCl. Gel-filtration chromatography of the high-salt extract and rechromatography in a low-salt solution indicated that the two proteins may be associated with each other. The association of the two proteins was suggested by cosedimentation of the G-protein with the actin gel formed by actin and ABP. The amounts of the cosedimented G-protein and ABP was unaffected by guanosine-5'-O-[beta-thio]diphosphate and guanosine-5'-O-[gamma-thio]triphosphate, but the G-protein, not ABP, was partially released from the actin gel by phosphorylating ABP with cAMP-dependent protein kinase. Thus, the association of the two proteins was affected by modification of ABP, but not by modification of G-proteins. The physiological significance of the possible association of the two proteins might be that the membrane skeleton functions as a modulator of the G-protein, rather than that the G-protein modulates the function of the membrane skeleton which comprises ABP.

Repression of serotonin secretion by an endogenous Ca2(+)-activated protease in electropermeabilized bovine platelets.

Micromolar levels of free calcium ions added to the extracellular medium elicit secretion of serotonin from electropermeabilized bovine platelets in the presence of millimolar levels of Mg-ATP. Such Ca2(+)-dependent secretion of serotonin was almost completely impaired when the permeabilized platelets were preincubated for 1 min at 35 degrees C in 100 microM Ca2+ without Mg-ATP. The half-maximal effect was observed with about 45 microM Ca2+ in the preincubation medium. Inhibitors of serine-thiol protease, such as leupeptin and antipain, suppressed the impairment of the secretion of serotonin by the preincubation with Ca2+. Electron microscopic observation revealed that disorganization of the cytoskeletal structures, in particular of the membrane undercoat and the network of microfilaments, accompanied the impairment of secretion of serotonin. Microfilaments were also found to be dissociated from dense granules that contained serotonin. These morphological changes were also suppressed when antipain was included in the Ca2(+)-preincubation medium. Coincident with these morphological changes, the following biochemical changes were observed in 100 microM Ca2+ but not in the presence of Ca2+ and antipain. The amount of Triton-insoluble cytoskeleton and the acto-myosin content of the dense-granule fraction were markedly decreased. The decrease in Triton-insoluble cytoskeletons was quantitatively correlated with the degree of impairment of secretion of serotonin. Immunoblot analysis of EGTA extracts of the cells showed that the 240-kDa spectrin in platelets was degraded to a 235-kDa fragment, and a 260-kDa actin-binding protein (ABP) in platelets was partially degraded to 190- and 110-kDa components.(ABSTRACT TRUNCATED AT 250 WORDS)

Distinct occurrence of phosphatidylinositol 4,5-bisphosphate-induced Ca2+ release and inositol 1,4,5-triphosphate-induced release in ATP-dependent Ca2+-transporting platelet microsomes.

The effects of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and inositol 1,4,5-triphosphate(InsP3) on the Ca2+ release from ATP-dependent Ca2+-transporting microsomes prepared from ox platelets were investigated. Under optimal conditions, both PtdInsP2 and InsP3 released Ca2+ from the microsomes in a similar dose-dependent manner. However, the maximal amount of Ca2+ released by InsP3 was almost one-fourth of that released by PtdInsP2. Neither PtdInsP2 nor InsP3 appeared to act as a Ca2+ ionophore since they showed no effect on the Ca2+ content of liposomes prepared from platelet microsomal lipids. InsP3-induced but not PtdInsP2-induced Ca2+ release was decreased with increasing extravesicular Ca2+ from 0.1 microM to 10 microM and it was completely inhibited by 10 microM Ca2+. PtdInsP2-induced but not InsP3-induced Ca2+ release was markedly inhibited by Mg2+, ruthenium red and neomycin. In addition, InsP3 could induce no additional Ca2+ release after the accumulated Ca2+ had been maximally released by PtdInsP2. These results indicate that PtdInsP2 releases Ca2+ from platelet microsomes more effectively than InsP3 by a mechanism distinct from that of InsP3-induced release, and further that InsP3-sensitive microsomes are included within the population of PtdInsP2-sensitive microsomes.