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Phosphorylation of KRT8 (keratin 8) by excessive mechanical load-activated PKN (protein kinase N) impairs autophagosome initiation and contributes to disc degeneration
This study validates a protective role of Krt8 during overloading-induced IDD and demonstrates that targeting overloading activation of PKNs could be a novel and effective approach to mechano stress-induced pathologies with a wider window of therapeutic opportunity.Abbreviations: AAV: adeno-associated virus; AF: anulus fibrosus; ANOVA: analysis of variance; ATG: autophagy related; BSA: bovine serum albumin; cDNA: complementary deoxyribonucleic acid; CEP: cartilaginous endplates; CHX: cycloheximide; cKO: conditional knockout; Cor: coronal plane; CT: computed tomography; Cy: coccygeal vertebra; D: aspartic acid; DEG: differe...
Source: Autophagy - March 10, 2023 Category: Cytology Authors: Di Wang Qiliang Shang Jianxin Mao Chu Gao Jie Wang Dong Wang Han Wang Haoruo Jia Pandi Peng Mu Du Zhuojing Luo Liu Yang Source Type: research

siRNA high throughput screening identifies regulators of chloropicrin and hydrogen fluoride injury in human corneal epithelial cell models
Exp Eye Res. 2022 Jul 9:109169. doi: 10.1016/j.exer.2022.109169. Online ahead of print.ABSTRACTCorneal injuries induced by various toxicants result in similar clinical presentations such as corneal opacity and neovascularization. Many studies suggest that several weeks post-exposure a convergence of the molecular mechanisms drives these progressive pathologies. However, chemical agents vary in toxicological properties, and early molecular responses are anticipated to be somewhat dissimilar for different toxicants. We chose 3120 targets from the Dharmacon Human Druggable genome to screen for chloropicrin (CP) and hydrogen f...
Source: Cell Research - July 12, 2022 Category: Cytology Authors: Albert L Ruff Robert D Causey Jeffrey A Koenig Cristina V LaGrasta Amber M Gomez Bailey T Chalmers John G Lehman Source Type: research

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.
Abstract Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity...
Source: Autophagy - March 26, 2019 Category: Cytology Authors: Fernandez-Mosquera L, Yambire KF, Couto R, Pereyra L, Pabis K, Ponsford AH, Diogo CV, Stagi M, Milosevic I, Raimundo N Tags: Autophagy Source Type: research

Coagulation factor XI induces Ca2+ response and accelerates cell migration in vascular smooth muscle cells via proteinase-activated receptor 1.
In conclusion, FXIa mainly elicits Ca2+ signal via the PAR1/CaV1.2-mediated Ca2+ influx and accelerates the migration in vascular smooth muscle cells. The present study provides the first evidence that FXIa exerts a direct cellular effect on vascular smooth muscle. PMID: 30566391 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - December 19, 2018 Category: Cytology Authors: Liu W, Hashimoto T, Yamashita T, Hirano K Tags: Am J Physiol Cell Physiol Source Type: research

Wnt-RhoA Signaling Pathways in Fluoride-Treated Ameloblast-Lineage Cells
This study examined the effect of sodium fluoride (NaF) on the Wnt and RhoA signaling pathways in murine ameloblast-lineage cells (ALCs) to better understand the developmental mechanisms of dental fluorosis. Wnt and Rho pathway activities were investigated when ALCs were treated with 1.5 mM NaF, dickkopf-related protein-1 (Dkk-1), secreted frizzled related-protein-2 (sFRP-2), β-catenin siRNA dominant negative RhoA (RhoADN) plasmid and Y-27632. Wnt pathway activity was investigated via RT-PCR, Western blot and Topflash luciferase assay. The activity of the RhoA pathway was analyzed via Rho pull-down assay and immunoprecipi...
Source: Cells Tissues Organs - November 14, 2014 Category: Cytology Source Type: research