Phosphatidylinositol-4, 5-bisphosphate [PI(4,5)P(2)] has been implicated in the priming of large dense-core vesicles in many secretory cells; however, its role in the Ca(2+)-dependent secretory activity in pituitary cells remains elusive. We assessed the effect of elevated intracellular PI(4,5)P(2) on the kinetics of Ca(2+)-dependent exocytosis, using a whole-cell patch-clamp technique in wild-type mouse melanotrophs from fresh pituitary tissue slices. We found that 1 micromol/L PI(4,5)P(2) significantly increased Ca(2+)-dependent exocytosis of vesicles that need to go through ATP-dependent reactions; however, the exocytosis of release-ready vesicles (ATP-independent release) and voltage-activated Ca(2+) currents remained unaffected. We suggest that PI(4,5)P(2) increases the size of the readily releasable vesicle pool by regulating the effectiveness of vesicular mobilization and fusion in an ATP-dependent manner.
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http://dx.doi.org/10.1111/j.1749-6632.2008.04002.x | DOI Listing |
Nat Commun
January 2025
Center for Research Informatics, The University of Chicago, Chicago, IL, USA.
The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and menstrual cycle.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Molecular Medicine, Inha University, Incheon, Republic of Korea.
Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its transcription and glycosylation.
View Article and Find Full Text PDFElife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
USC School of Pharmacy, Los Angeles, CA, USA.
Background: Cellular senescence is a hallmark of aging and has been implicated in several neurodegenerative diseases including Alzheimer's disease (AD). Senescence cells undergo changes in gene expression and metabolism and can exhibit a so-called "senescence-associated secretory phenotype" (SASP) characterized by increased secretion of pro-inflammatory molecules and factors which can damage nearby cells, contributing to AD pathology progression.
Method: In this study, we determined mechanisms of cellular senescence using human postmortem brain samples, cellular models, and APOE4 animal models.
Alzheimers Dement
December 2024
University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Background: Cellular senescence is defined as cell cycle arrest and the acquisition of a proinflammatory 'senescence-associated secretory phenotype' (SASP). In Alzheimer's disease (AD), tau protein in neurons undergoes hyperphosphorylation and misfolding, resulting in the formation of pathogenic soluble aggregates known as tau oligomers. Tau oligomers are released from neurons during neuronal activation and are transmitted to postsynaptic cells in a prion-like fashion.
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