scholarly journals cAMP-dependent recruitment of acidic organelles for Ca2+ signaling in the salivary gland

2016 ◽  
Vol 311 (5) ◽  
pp. C697-C709 ◽  
Author(s):  
John F. Imbery ◽  
Sumit Bhattacharya ◽  
Sura Khuder ◽  
Amanda Weiss ◽  
Priyodarshan Goswamee ◽  
...  

Autonomic neural activation of intracellular Ca2+ release in parotid acinar cells induces the secretion of the fluid and protein components of primary saliva critical for maintaining overall oral homeostasis. In the current study, we profiled the role of acidic organelles in shaping the Ca2+ signals of parotid acini using a variety of imaging and pharmacological approaches. Results demonstrate that zymogen granules predominate as an apically polarized population of acidic organelles that contributes to the initial Ca2+ release. Moreover, we provide evidence that indicates a role for the intracellular messenger NAADP in the release of Ca2+ from acidic organelles following elevation of cAMP. Our data are consistent with the “trigger” hypothesis where localized release of Ca2+ sensitizes canonical intracellular Ca2+ channels to enhance signals from the endoplasmic reticulum. Release from acidic stores may be important for initiating saliva secretion at low levels of stimulation and a potential therapeutic target to augment secretory activity in hypofunctioning salivary glands.

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1547 ◽  
Author(s):  
Claudia D’Agostino ◽  
Osama A. Elkashty ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Simon D. Tran ◽  
...  

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.


2017 ◽  
Vol 76 (4) ◽  
pp. 145-153 ◽  
Author(s):  
Jana Nikitin ◽  
Alexandra M. Freund

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.


2016 ◽  
Vol 37 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Hasida Ben-Zur

Abstract. The current study investigated the associations of psychological resources, social comparisons, and temporal comparisons with general wellbeing. The sample included 142 community participants (47.9% men; age range 23–83 years), who compared themselves with others, and with their younger selves, on eight dimensions (e.g., physical health, resilience). They also completed questionnaires assessing psychological resources of mastery and self-esteem, and three components of subjective wellbeing: life satisfaction and negative and positive affect. The main results showed that high levels of psychological resources contributed to wellbeing, with self-enhancing social and temporal comparisons moderating the effects of resources on certain wellbeing components. Specifically, under low levels of mastery or self-esteem self-enhancing social or temporal comparisons were related to either higher life satisfaction or positive affect. The results highlight the role of resources and comparisons in promoting people’s wellbeing, and suggest that self-enhancing comparisons function as cognitive coping mechanisms when psychological resources are low.


2020 ◽  
Vol 18 (1) ◽  
pp. 23-37
Author(s):  
Andreea Gheorghe ◽  
Oana Fodor ◽  
Anișoara Pavelea

This study explores the association between task conflict and team creativity and the role of group cognitive complexity (GCC) as a potential explanatory mechanism in a sample of 159 students organized in 49 groups. Moreover, we analyzed the moderating effect of collective emotional intelligence (CEI)in the relationship between task conflict and GCC.As hypothesized, we found that task conflict has a nonlinear relationship with GCC, but contrary to our expectations, it follows a U-shaped association, not an inversed U-shape. In addition,the moderating role of CEI was significant only at low levels. Contrary to our expectation, the mediating role of GCC did not receive empirical support. Theoretical and practical contributions are discussed.


2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Lan Jin ◽  
Yunhe Chen ◽  
Dan Cheng ◽  
Zhikai He ◽  
Xinyi Shi ◽  
...  

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.


Author(s):  
Shanna Hamilton ◽  
Roland Veress ◽  
Andriy Belevych ◽  
Dmitry Terentyev

AbstractSudden cardiac death due to malignant ventricular arrhythmias remains the major cause of mortality in the postindustrial world. Defective intracellular Ca2+ homeostasis has been well established as a key contributing factor to the enhanced propensity for arrhythmia in acquired cardiac disease, such as heart failure or diabetic cardiomyopathy. More recent advances provide a strong basis to the emerging view that hereditary cardiac arrhythmia syndromes are accompanied by maladaptive remodeling of Ca2+ homeostasis which substantially increases arrhythmic risk. This brief review will focus on functional changes in elements of Ca2+ handling machinery in cardiomyocytes that occur secondary to genetic mutations associated with catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome.


Author(s):  
Haocheng Luo ◽  
Qingqi Liu ◽  
Chengfu Yu ◽  
Yangang Nie

Parental warmth plays an important role in the development of adolescents’ physical and mental health. There are numerous empirical studies indicating a relationship between parental warmth and prosocial behavior among adolescents, although the underlying mechanisms of this association remain unclear. Adopting a longitudinal design across two time points, the present study proposes a moderated mediation model to explore the mediating role of gratitude and the moderating role of the school climate between parental warmth and prosocial behavior. The sample consisted of 943 participants (483 boys and 451 girls) who participated in the second assessment and completed questionnaires assessing gratitude, school climate, and prosocial behavior in April 2019. Their parents participated in the first assessment and completed a questionnaire pertaining to parental warmth in October 2018. After controlling for the gender and age of the adolescents, the results showed that the positive association between parental warmth and prosocial behavior is mediated by gratitude, and school climate does play a moderating role in the second half of the mediating path. Specifically, the school climate can play a protective role in adolescents with low levels of gratitude. For adolescents with less gratitude, a strong school climate can promote more prosocial behaviors and can effectively alleviate the negative prediction of low levels of gratitude. This study provides a theoretical explanation for the generation of adolescents’ prosocial behavior and provides theoretical guidance for the interventions of schools and parents.


2021 ◽  
Author(s):  
Xue Wang ◽  
Yuetong Wang ◽  
Zhaoyuan Fang ◽  
Hua Wang ◽  
Jian Zhang ◽  
...  

Abstract Somatic mutations of the chromatin remodeling gene ARID2 are observed in about 7% of human lung adenocarcinoma (LUAD). However, the role of ARID2 in the pathogenesis of LUAD remains largely unknown. Here we find that ARID2 expression is decreased during the malignant progression of both human and mice LUAD. Using two KrasG12D-based genetically engineered murine models (GEMM), we demonstrate that ARID2 knockout significantly promotes lung cancer malignant progression and shortens the overall survival. Consistently, ARID2 knockdown significantly promotes cell proliferation in human and mice lung cancer cells. Through integrative analyses of Chip-Seq and RNA-Seq data, we find that Hspa1a is up-regulated by Arid2 loss. Knockdown of Hspa1a specifically inhibits malignant progression of Arid2-deficient but not Arid2-wt lung cancers in both cell lines as well as animal models. Treatment with Hspa1a inhibitor could significantly inhibit the malignant progression of lung cancer with Arid2 deficiency. Together, our findings establish ARID2 as an important tumor suppressor in LUAD with novel mechanistic insights, and further identify HSPA1A as a potential therapeutic target in ARID2-deficient LUAD.


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