Zn2+ stimulates salivary secretions via metabotropic zinc receptor ZnR/GPR39 in human salivary gland cells

Kim, Yun Joong; Jo, Youhwa; Lee, Yeon-Hee; Park, Kyungpyo; Park, Heekyung; Choi, Se‐Young

doi:10.1038/s41598-019-54173-3

Cited by 15 publications

(18 citation statements)

References 31 publications

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“…Since human salivary glands express ACE2 and TMPRSS2, salivary gland infection with SARS-CoV-2 would affect saliva secretion, thereby altering the tasting ability. Zinc increases the secretion of unstimulated and stimulated whole saliva in humans [ 172 ]. Conversely, zinc deficiency associated with COVID-19 may induce gustatory dysfunction through hyposalivation.…”

Section: Possible Mechanisms Of Gustatory Dysfunctionmentioning

confidence: 99%

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Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review

Tsuchiya

2021

Dentistry Journal

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Since the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, management of coronavirus disease 2019 (COVID-19) has been challenging for healthcare providers. The oral cavity is referred to as a target of SARS-CoV-2. The aim of this study was to review oral symptoms specific to COVID-19 patients from the point of view of symptom prevalence and pathogenesis and to speculate the pathogenic mechanisms underlying them. Scientific articles were retrieved by searching PubMed/MEDLINE, Google Scholar, medRxiv, and bioRxiv from 3 February 2020 to 31 December 2020, and they were reviewed by title, abstract, and text for relevance. The literature search indicated that COVID-19 patients frequently present with gustatory dysfunction, xerostomia, and oral mucosal lesions, while their prevalence is likely to vary by country, age, gender, and disease severity. Gustatory dysfunction and xerostomia appear at an early stage of SARS-CoV-2 infection and last relatively long. One of possible pathogenic mechanisms of both symptoms is attributed to the expression of viral cellular entry-relevant receptors in taste cells and salivary glands. Dental professionals who can first become aware of oral symptoms associated with COVID-19 will play a more active role in and make a greater contribution to diagnosis and prevention of COVID-19.

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Section: Possible Mechanisms Of Gustatory Dysfunctionmentioning

confidence: 99%

“…Kim et al [ 172 ] collected unstimulated and stimulated whole saliva from patients with hyposalivation, Sjögren syndrome patients, and healthy subjects. Mouth rinsing with 0.25% ZnCl 2 solution increased both saliva in all groups, indicating that zinc stimulates saliva secretion.…”

Section: Possible Mechanisms Of Xerostomiamentioning

confidence: 99%

Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review

Tsuchiya

2021

Dentistry Journal

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“…Zn 2+ has been indicated to have a role in salivary secretion disorders and taste [ 154 ] and is found in the secretory granules of the salivary glands [ 155 ]. GPR39 signaling was shown to take place in ductal salivary gland cells (HSY) [ 24 , 27 ] and later in human submandibular glands and gland cells (HSGs) [ 156 ]. Recently, a ZnCl 2 solution was shown to trigger saliva secretion in humans and using human submandibular gland cells, Zn 2+ was shown to induce the intracellular Ca 2+ response and aquaporin-5 translocation to the plasma membrane [ 156 ], both in a key role in salivary secretion regulation [ 157 , 158 ].…”

Section: Physiological Functions Of Gpr39mentioning

confidence: 99%

“…GPR39 signaling was shown to take place in ductal salivary gland cells (HSY) [ 24 , 27 ] and later in human submandibular glands and gland cells (HSGs) [ 156 ]. Recently, a ZnCl 2 solution was shown to trigger saliva secretion in humans and using human submandibular gland cells, Zn 2+ was shown to induce the intracellular Ca 2+ response and aquaporin-5 translocation to the plasma membrane [ 156 ], both in a key role in salivary secretion regulation [ 157 , 158 ]. The effects were shown to be GPR39-mediated by their drastic reduction in GPR39 knockdown cells [ 156 ].…”

Section: Physiological Functions Of Gpr39mentioning

confidence: 99%

“…Recently, a ZnCl 2 solution was shown to trigger saliva secretion in humans and using human submandibular gland cells, Zn 2+ was shown to induce the intracellular Ca 2+ response and aquaporin-5 translocation to the plasma membrane [ 156 ], both in a key role in salivary secretion regulation [ 157 , 158 ]. The effects were shown to be GPR39-mediated by their drastic reduction in GPR39 knockdown cells [ 156 ]. GPR39 expression has also been reported in the sperm tail and the acrosome [ 159 , 160 ] and Zn 2+ -induced GPR39 activation was shown to stimulate sperm acrosomal exocytosis [ 160 ] and hyper-activated motility [ 159 ].…”

Section: Physiological Functions Of Gpr39mentioning

confidence: 99%

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The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target

Laitakari

Liu

Frimurer

et al. 2021

IJMS

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The G-protein coupled receptor GPR39 is abundantly expressed in various tissues and can be activated by changes in extracellular Zn2+ in physiological concentrations. Previously, genetically modified rodent models have been able to shed some light on the physiological functions of GPR39, and more recently the utilization of novel synthetic agonists has led to the unraveling of several new functions in the variety of tissues GPR39 is expressed. Indeed, GPR39 seems to be involved in many important metabolic and endocrine functions, but also to play a part in inflammation, cardiovascular diseases, saliva secretion, bone formation, male fertility, addictive and depression disorders and cancer. These new discoveries offer opportunities for the development of novel therapeutic approaches against many diseases where efficient therapeutics are still lacking. This review focuses on Zn2+ as an endogenous ligand as well as on the novel synthetic agonists of GPR39, placing special emphasis on the recently discovered physiological functions and discusses their pharmacological potential.

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Galvanization of Protein–Protein Interactions in a Dynamic Zinc Interactome

Kocyła

Tran

Krężel

2021

Trends in Biochemical Sciences

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The presence of Zn 2+ at protein-protein interfaces modulates complex function, stability, and introduces structural flexibility/complexity, chemical selectivity, and reversibility driven in a Zn 2+ -dependent manner. Recent studies have demonstrated that dynamically changing Zn 2+ affects numerous cellular processes, including protein-protein communication and protein complex assembly. How Zn 2+ -involved protein-protein interactions (ZPPIs) are formed and dissociate and how their stability and reactivity are driven in a zinc interactome remain poorly understood, mostly due to experimental obstacles. Here, we review recent research advances on the role of Zn 2+ in the formation of interprotein sites, their architecture, function, and stability. Moreover, we underline the importance of zinc networks in intersystemic communication and highlight bioinformatic and experimental challenges required for the identification and investigation of ZPPIs. Protein-Protein Interactome and the Role of Metal IonsA complete picture of protein-protein interactions (PPIs), also known as the protein-protein interactome (see Glossary), is crucial to understand cell molecular machinery at the system biology level [1-3]. Identification of protein molecular complexes requires the description of various aspects, such as composition, component affinity, and lifetime with series of spatial and physicochemical properties describing the interface between proteins. Considering both the affinity and lifetime of proteins to interact, obligate and nonobligate complexes can be found, where the latter are divided into permanent (mostly strong, irreversible) and transient (reversible, frequently with medium affinity). Transient complexes are characterized by smaller interfaces, frequently dependent on specific recognition patterns, where the limited surface meets the requirement of constituents to fold and exist independently without aggregation [4,5]. Their interfaces contain more residues of higher polarity stabilized by salt bridges and hydrogen bonds with more chain turns to gain flexibility [6][7][8]. The specificity of such interactions is also elevated by the utilization of the same interface for multiple interactions across evolution, where the local environment has been affecting the fast adaptation of mutations [9,10].

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Zn2+ stimulates salivary secretions via metabotropic zinc receptor ZnR/GPR39 in human salivary gland cells

Cited by 15 publications

References 31 publications

Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review

Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review

The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target

Galvanization of Protein–Protein Interactions in a Dynamic Zinc Interactome

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