Intracellular zinc during cell activation and zinc deficiency

ABSTRACT A component of the cellular response to zinc deficiency operates via control of transcript abundance. Therefore, microarray analysis was employed to identify Schizosaccharomyces pombe genes whose mRNA levels are regulated by intracellular zinc status. A set of 57 genes whose mRNA levels were substantially reduced in response to zinc deficiency was identified, while the mRNA levels of 63 genes were increased by this condition. In order to investigate the mechanisms that control these responses, a genetic screen was employed to identify mutants with defective zinc-responsive gene expression. Two strains (II-1 and V7) that were identified by this screen harbor mutations that are linked to zrt1 +, which encodes a putative Zrt/IRT-like protein (ZIP) zinc uptake transporter. Importantly, zrt1 + mRNA levels are increased in response to zinc deprivation, and cells lacking functional Zrt1 are highly impaired in their ability to proliferate at limiting zinc concentrations. Furthermore, zrt1 null cells were found to have severely reduced zinc contents, indicating that Zrt1 functions as a key regulator of intracellular zinc levels in fission yeast. The deletion of fet4 +, another zinc-responsive gene encoding a putative metal ion transporter, exacerbated the phenotypes associated with the loss of Zrt1, suggesting that Fet4 also plays a role in zinc uptake under limiting conditions.

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Pharmacological Properties of Zinc Drugs

Ukraïnsʹkij žurnal medicini bìologìï ta sportu ◽

10.26693/jmbs06.03.037 ◽

2021 ◽

Vol 6 (3) ◽

pp. 37-44

Author(s):

G. V. Zaychenko ◽

◽

N. A. Gorchakova ◽

O. V. Shumeiko ◽

O. V. Klymenko ◽

...

Keyword(s):

Zinc Deficiency ◽

Liver Diseases ◽

Positive Impact ◽

Antioxidant Properties ◽

Gastrointestinal Diseases ◽

Synaptic Activity ◽

Zinc Homeostasis ◽

Human Organism ◽

Main Role ◽

Intracellular Zinc

The review represents data about biochemical and physiological zinc properties, its pharmacological influence. Among the trace elements, zinc is one of the most used elements in biology and medicine. Zinc preserves molecular integration, influences the growth and division of cells, is included in some enzymes. Metallothioneins bind zinc with high affinity and serve as intracellular zinc reservoir. They may release free intracellular zinc when needed and mediate physiological zinc role, maintain zinc homeostasis in brain synaptic activity. Metallothioneins are strong radical scavengers that is why zinc plays the main role in oxidative stress. It is intracellular regulator, which influences apoptosis, osteogenesis, keratogenesis, provides intracellular support to proteins during molecular integration. It is a structural component in nucleonic acids and gene regulator proteins. Zinc deficiency has been detected in neurological and psychic diseases. Zinc supplement was effective in patients with stroke and brain injury. Zinc has a positive impact on memory and reduces hyperactivity in children. Zinc is involved in signals neurotransmission. Its deficiency in brain is connected with Alzheimer`s disease, depression, schizophrenia that is why it is used for the treatment of these diseases. Vitamin C is the zinc synergist in the treatment of neurological and psychic diseases as it has antioxidant properties, takes place in detoxication. Zinc plays the important role in autistic disorders in children and is included in the pharmacotherapy of this status. Zinc deficiency leads to liver diseases, hepatitis, liver cirrhosis and gastrointestinal disturbances such as appetite loss, diarrhea, and anorexia. In chronic liver diseases, zinc corrects amino acids disbalance, capacity to synthesize albumin, metabolize ammonium. It was shown that zinc as a heavy metal has antimicrobial action in diarrheas, cholera and other gastrointestinal diseases. It was detected that zinc has antiviral effects in herpes diseases and diseases of upper respiratory ways. Conclusion. Zinc deficiency is connected with some autoimmune diseases such as asthma, eczema and other dermatological diseases. The supply of human organism with zinc and vitamins A, C, D and E is a promising approach because it is a cofactor of 118 proteins aimed at antiviral protection of the human body including interferon-1-dependent proteins against coronavirus. It was shown that zinc helps to inhibit «cytokine storm» characteristic of COVID-19, reduces chronic systemic inflammation and compensates for comorbid pathologies of cardiovascular system in patients with COVID-19. Zinc may influence other systems such as reproductive function, pregnancy, fetus, testosterone synthesis

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Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death

Biochemical Journal ◽

10.1042/bj20040074 ◽

2004 ◽

Vol 383 (1) ◽

pp. 63-71 ◽

Cited By ~ 26

Author(s):

Susan S. CHOU ◽

Michael S. CLEGG ◽

Tony Y. MOMMA ◽

Brad J. NILES ◽

Jodie Y. DUFFY ◽

...

Keyword(s):

Cell Death ◽

Zinc Deficiency ◽

Caspase 3 ◽

Zinc Content ◽

Cell Number ◽

Intracellular Zinc ◽

Deficient Medium ◽

Zinc Concentrations ◽

Cells Cultured ◽

Deficient Group

Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1–C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-α, whereas PKC-α phosphorylation was not altered. Inhibition of PKC-α with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-δ, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-δ fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-δ inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-δ, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-δ to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

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Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162326 ◽

1990 ◽

Vol 48 (3) ◽

pp. 952-953

Author(s):

Gemma A.J. Kuijpers ◽

Harvey B. Pollard

Keyword(s):

Adrenal Medulla ◽

Calcium Binding ◽

Chromaffin Cells ◽

Cell Activation ◽

Structural Information ◽

Dependent Manner ◽

Chromaffin Granules ◽

Immuno Electron Microscopy ◽

Ultrathin Sections ◽

Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

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