Gut-derived 5-hydroxytryptamine (5-HT) is well known for its role in mediating colonic motility function. However, it is not very clear whether brain-derived 5-HT is involved in the regulation of colonic motility. In this study, we used central 5-HT knockout (KO) mice to investigate whether brain-derived 5-HT mediates colonic motility, and if so, whether it involves oxytocin (OT) production in the hypothalamus and OT receptor in the colon. Colon transit time was prolonged in KO mice. The OT levels in the hypothalamus and serum were decreased significantly in the KO mice compared to wild-type (WT) controls. OT increased colonic smooth muscle contraction in both KO and WT mice, and the effects were blocked by OT receptor antagonist and tetrodotoxin but not by hexamethonium or atropine. Importantly, the OT-induced colonic smooth muscle contraction was decreased significantly in the KO mice relative to WT. The OT receptor expression of colon was detected in colonic myenteric plexus of mice. Central 5-HT is involved in the modulation of colonic motility which may modulate through its regulation of OT synthesis in the hypothalamus. Our results reveal a central 5-HT - hypothalamus OT - colonic OT receptor axis, providing a new target for the treatment of brain-gut dysfunction. 相似文献
Asthenozoospermia is a common cause of male infertility, but in most cases its etiology is unknown. The exocytic cell vesicles called seminal extracellular vesicles in the human seminal fluid have been reported to play a pivotal role in promoting the motility of spermatozoa, and functional disorder of seminal extracellular vesicles may cause male infertility. To determine whether abnormal seminal extracellular vesicles are involved in asthenozoospermia, the differential abundance proteins between normozoospermic (NSEV) and asthenozoospermic seminal extracellular vesicles (ASEV) samples were analyzed by iTRAQ coupled with two‐dimensional liquid chromatography–tandem mass spectrometry. A total of 3,699 proteins were identified in the seminal extracellular vesicles (false discovery rate <0.01). Overall, 11 proteins were significantly upregulated (>1.2) in ASEV and 80 were significantly downregulated (<0.833). Functional bioinformatic analysis showed that these proteins with differential abundance were mainly associated with transport, metabolism, and signal pathways. The changes of OPTN, SMYD2, EIF2B2, TRPV6, ACE, PRSS8, and PPAP2A in ASEV were verified by western blot analysis, and we found that the abundance of TRPV6 markedly reduced in the seminal extracellular vesicles and ejaculated spermatozoa of asthenozoospermic patients, which indicated trpv6 was important in sperm motility. This study provides deeper insight into the involvement of seminal extracellular vesicles in asthenozoospermia and should aid the search for novel biomarkers of male infertility. 相似文献
The longest part of the sperm flagellum, the principal piece, contains the fibrous sheath, a cytoskeletal element unique to spermiogenesis. We performed mass spectrometry proteomics on isolated human fibrous sheaths identifying a unique ADP/ATP carrier protein, SFEC [AAC4], seven glycolytic enzymes previously unreported in the human sperm fibrous sheath, and sorbitol dehydrogenase. SFEC, pyruvate kinase and aldolase were co-localized by immunofluorescence to the principal piece. A homology model constructed for SFEC predicted unique residues at the entrance to the nucleotide binding pocket of SFEC that are absent in other human ADP/ATP carriers, suggesting opportunities for selective drug targeting. This study provides the first evidence of a role for an ADP/ATP carrier family member in glycolysis. The co-localization of SFEC and glycolytic enzymes in the fibrous sheath supports a growing literature that the principal piece of the flagellum is capable of generating and regulating ATP independently from mitochondrial oxidation in the mid-piece. A model is proposed that the fibrous sheath represents a highly ordered complex, analogous to the electron transport chain, in which adjacent enzymes in the glycolytic pathway are assembled to permit efficient flux of energy substrates and products with SFEC serving to mediate energy generating and energy consuming processes in the distal flagellum, possibly as a nucleotide shuttle between flagellar glycolysis, protein phosphorylation and mechanisms of motility. 相似文献
Three slit genes, slit1 to slit3, have been cloned to date. Slit1 and slit2 act as chemorepellent factors for axon guidance. Slit3 is involved in the formation of the diaphragm and kidney during embryogenesis. However, its molecular function remains unclear. We found that slit3 expression was induced by lipopolysaccharide (LPS)-stimulation in macrophages and that it was localized in the mitochondria and along the plasma membrane. Silencing of slit3 expression by RNA interference reduced cell motility and Rac/Cdc42 activation. These results suggest that slit3 functions as an intracellular signaling molecule for cell motility as part of the LPS-induced signaling cascade. 相似文献
Early localization of C. elegans founder cell descendents in certain regions of embryo has been documented. The purpose of this investigation is to evaluate the onset of ABp and EMS descendent cell regionalization in the embryo using the random motility coefficient as a quantitative parameter. The forward migration index (FMI) was also calculated in order to evaluate the chemotatic biases of ABp-dc and EMS-dc during regionalization.
The results showed that the random motility coefficient declined as the cells tended to regionalize. The mean squared displacement (MSD) versus time plot showed a non-linear model which indicated non-random cell movement. FMI showed progressive increase as the cells tended to regionalized, and it was significantly higher in EMS-dc than ABp-dc, moreover the chemotatic biases were higher in EMS-dc than ABp-dc.
The circular plots showed that the statistical differences between the two lineages were significant, while ABp-dc showed significant differences in xy, xz and yz planes; EMS derived cells showed no significant differences except in yz planes. The conclusion of this study is that the onset of early regionalization occurs in EMS-dc sooner than in ABp-dc. 相似文献
This study revealed that a Pseudomonas aeruginosa tonB1 mutant was unable to produce a mature biofilm and showed reduced swarming and twitching motilities compared with the parent strain. The tonB1 mutant was also found to produce significantly lower cell-free and cell-associated levels of the quorum sensing (QS) signal molecule 3-oxo-C12-AHL. Altered biofilm and motility phenotypes were restored to wildtype with the addition of exogenous N-acylhomoserine lactones. These functions were independent of the role of TonB1 in iron uptake. This is the first time that a link has been established between TonB1 activity and QS. 相似文献
Fourteen Xylella fastidiosa isolates from grapevines exhibiting Pierce's disease symptoms in California, Texas, and South Carolina were examined for type IV pilus-mediated twitching motility, a phenotype previously observed in a Temecula isolate from California. All isolates except one from South Carolina (SC 19A97) exhibited colonies with a peripheral fringe on PW agar, a feature indicative of twitching motility; however, when individual cells of SC 19A97 were examined at higher magnifications twitching motility was observed. The presence and width of colony peripheral fringes were related to the amount of bovine serum albumin (BSA) present in the medium; no or low levels of BSA (0-1.8 g L(-1)) permitted development of the widest fringe, whereas higher levels (3.5-6.0 g L(-1)) severely limited, and in many instances prevented, peripheral fringe development. The growth rate of the wild-type Temecula isolate in PW broth with different concentrations of BSA was similar for all tested concentrations of BSA; however, growth was significantly reduced in medium without BSA. 相似文献