A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

Studies on the binding properties of Zn2+ ion to quercetin and the antioxidant ac-tivi ties / 药学实践杂志

Objective To study the anti-oxidation properties of Zn2+-quercetin complexes .Methods The binding stoi-chiometric ratios and the binding constant of Zn2+ to quercetin were measured with UV-Vis spectroscopy .The binding sites on quercetin were determined via1 H NMR spectroscopy .The antioxidant activities of Zn2+-quercetin complexes were compared to quercetin by scavenging DPPH radical method .The binding ratio of Zn2+ to quercetin depends on neutralization of phenol groups of quercetin .Results The binding ratio of Zn2+ to quercetin is 1:2 when less than two OH groups were deprotonated . The binding ratio is 1:1 when more than three OH groups were deprotonated .The apparent binding constant is 2 .42 × 106 M -1 for the 1:1 Zn2+-quercetin complex .The 3′-OH and 4′-OH of quercetin are involved in the Zn2+ binding .The scavenging DPPH radical activity of Zn2+-quercetin complex is 2 .3 times of quercetin .Conclusion These results provide a new insight to expand applications of this traditional Chinese medicine .

Effects of Zn2+and Zn2+-coordinating glutamic acid residues on the superantigenic activities of staph-ylococcal enterotoxin C2 / 中华微生物学和免疫学杂志

Objective To investigate the role of Zn 2+and Zn2+-coordinating glutamic acid residues ( 71Glu and 80Glu ) in the superantigenic activities of staphylococcal enterotoxin C2 ( SEC2 ) .Methods Over-lap PCR was used to amply genes encoding recombinant mutant proteins rSEC 2 ( E71A), rSEC2 (E80A) and rSEC2 (E71A/E80A).The mutant proteins were expressed in E.coli BL21 (DE3) and puri-fied by affinity chromatography .The differences of biological activities between rSEC 2 and its mutants were compared in vitro.The effects of Zn 2+on the superantigenic activities of rSEC 2 were evaluated by analyzing the proliferation of splenic lymphocytes in the presence or absence of ethylenediaminetetraacetic acid ( EDTA) .Results The substitution of glutamic acid residue at position 71 and 80 by alanine residue had no significant effects on the superantigenic activities and the conformational stability of rSEC 2 mutants.How-ever, traces of Zn2+(10μmol/L) could significantly enhance rSEC2-induced proliferation of splenic lympho-cytes, and only certain amount of Zn 2+could completely restore rSEC2-induced proliferation in the presence of EDTA.Conclusion This study indicated that mutations at Zn 2+-coordinating glutamic acid residues had no significant effects on the conformational stability and the superantigenic activities of SEC 2.Zn2+might play a role in regulating the superantigenic activities of SEC 2 through some indirect ways .

Aspectos fisiológicos del catión cinc y sus implicaciones cardiovasculares / Physiological aspects of Zn cathion and its cardiovascular implications

Introducción La versatilidad del catión cinc en la fisiología de diversos tipos celulares ha conllevado a una creciente atención de la comunidad científica sobre sus roles funcionales y la regulación a la que se encuentran sus niveles. Objetivos Presentar una revisión bibliográfica sobre el tema, con énfasis en las implicaciones cardiovasculares de este catión. Fuente de Datos El buscador Pubmed del Servicio Central de Información Biotecnológica de los Institutos Nacionales para la Ciencia, con el cual se localizaron y consultaron 52 artículos científicos. Resultados El catión cinc además de constituir un cofactor de numerosas enzimas (por ejemplo la anhidrasa carbónica) y consecuentemente estar implicado en diversos procesos metabólicos, participa como modulador de las sinapsis a través de su acción bloqueadora de diversos canales iónicos. Esto justifica que si bien su deficiencia puede acarrear trastornos en la fisiología del organismo, el exceso de este catión, incluso localmente, pudiera interferir con la actividad eléctrica de los tejidos excitables, entre ellos el miocardio. Conclusiones Es importante el estudio de los efectos cardioprotectores del cinc, pero a su vez, es necesario tener conocimiento de los mecanismos y las dosis mediante las cuales puede ejercer sus efectos nocivos.

Introduction Versatility of Zn+2 in the physiology of several cell types has led to growing attention by the scientific community on the functional roles and the regulation of this cation levels. Objectives To present a literature review on this topic, making emphasis on the cardiovascular implications of Zinc. Data source Pubmed from the Central Service of Biotechnological Information of the US National Institutes for Science (NCBI in English) from which 52 scientific articles were read. Results Cation Zinc is not only a co-factor for numerous enzymes (for example carbon anhydrase) and involved in several metabolic processes, but participates as modulator of synapses through its blocking action of various ion channels. This explains why, although the Zn deficiency may cause body physiology disorders, the excessive presence of this ion even locally could interfere in the electrical activity of excitable tissues such as the myocardium. Conclusions For these reasons, it is important to study the cardioprotective effects of Zinc, but at the same time, it is necessary to know the mechanisms and the doses through which it may have harmful impact.

EXPERIMENTAL. STUDY ON THE CHANGE OF K~+/Na~+ Mg~(2+)/Ca~(2+)、Zn~(2+)/Cu~(2+)RATIO IN CARDIAC MUSCLE WITH ACUTE MYOCARDIAL IN FARCTION / 中国法医学杂志

Using the animal model of acute myocardial infarction of rabbit after left coronary artery ligation, the authors studied the reltionship between the change of myocardial K~+/Na~+ ,Mg~(2+)/Ca~(2+), and Zn~(2+)/Cu~(2+) ratio and the time after acute myocardial infarction. The results demonstrated that. (1)the K+/Na~+ and Mg~(2+)/Ca~(2+)ratio dropped with prolongation of time myocardial ischemia. There was significant (P0.05)difference of Zn~(2+)/Cu~(2+) ratio between the experimental groups and the control group, but Zn~(2+)/Cu~(2+) ratio showed a tendency of dropping with prolongation of time of ischemia in the experimental group. At 120 min of myocardial ischemia,the Zn~(2+)/Cu~(2+) ratio was abour 1/2 as those at 15min, 30min, and 60min(P

Effects of Cu~(2+), Zn~(2+) and Mn~(2+)on postsynaptic sites / 中国药理学通报

Effects of Cu2+,Zn2+and Mn2+ on responses to ACh were studied with toad rec-tus abdominis. Cu2+, Zn2+and Mn2+concentra-tion- dependently shifted the concentration-response curves for ACh to the right unparallelly and reduced the maximal response considerably. The pAh values of Cu2+ , Zn2+ and Mn2+ were 3.69, 2.95 and 2. 62, respectively. The inhibitory potent of Cu2+ and Zn2+ seemed to be 11.7 times and 2. 1 times respectively more thanthat of Mn2+. It was suggested that Cu2+, Zn2+ and Mn2+postsynaptically interfere with the action of ACh. However, Zn2+in lower concentration shifted the bottom section of the curve for ACh to the left and top, and shifted the top section of the curve to the right, suggesting that Mn2+in lower concentration be possessed of partial agonistic property.

Ca2+ and the interaction of pore-formers with membranes.

The interaction of pore-forming agents, such as Sendai virus, influenza virus (at pH 5 3), activated complement, Staphylococcus aureus α-toxin, melittin and polylysine, with the surface membrane of cells has been studied. In each case the following changes are initiated: collapse of membrane potential, leakage of ions, and leakage of phosphorylated metabolites. The changes can be inihibited by extracellular Ca2+ at physiological concentration; Mg2+ is less effective, and Zn2+ is more effective, than Ca2+ Ca2+ appears to act at a stage subsequent to the binding of pore-forming agent to cells. It is concluded that divalent cations are able to protect cells against the damaging effects of certain viruses, toxins or the components of activated complement in a manner that is worthy of further investigation.

EFFECTS OF Zn~(2+) ON ISOLATED SUPERIOR CERVICAL SYMPATHETIC GANGLION OF RABBITS / 西安交通大学学报(医学版)

The effects of Zn~(2+) on the isolated superior cervical sympathetic ganglion of rabbit were stud ied with sucrese-gap method. It was found thatZn~(2+) significantly inhibited ganglienic action poten-tial with a manner of concentration-dependence.The IC-50 value was 1. 48 mmol/L. The effects ofZn~(2+) were antagonized by neostigmine and 1-cys-tein, reduced under high concentration of Ca~(2+) andenhanced under low concentration of Ca~(2+). It wasalso found that Zn~(2+) inhibited ganglionic N wave,less affected p wave and without any effect on LNwave.

Regulatory effect of Zn~(2+) on P2X receptor-mediated,ATP-induced currents in different autonomic ganglion neurons in rats / 第二军医大学学报

Objective:To compare the effects of Zn~(2+)onthe P2X receptor-mediated,ATP-induced currents in neurons separated from rat superior cervical ganglion(SCG),nodose ganglion(NG),and otic ganglion(OTG).Methods: Whole-cell patch clamp recording technique was used to study the regulatory effects of Zn~(2+) on ATP/??-me ATP-induced currents in the above 3 ganlglion neurons.Results: All SCG neurons responded to ATP with a sustained current,while no neurons responded to ??-me ATP;Zn~(2+) potentiated ATP-induced sustained currents to(1 442?34)% of the original value.All NG neurons responded to ATP and ??-me ATP with a similar sustained current;coapplication of Zn~(2+)(10 ?mol/L) potentiated their responses to(180?12)% and(262?28)%,respectively.All OTG neurons responded to both ATP and ??-me ATP with a sustained current.Coapplication of Zn~(2+)(10 ? mol/L) did not significantly potentiate the sustained currents induced by 10 ?mol/L ATP,but when ATP was at 30 ?mol/L,Zn~(2+)(10-100 ?mol/L) inhibited ATP-induced sustained currents in a dose dependent manner.If TNP-ATP(100 nmol/L) was first used to inhibit ATP-induced current to(26?2)% of the original value,Zn~(2+) at 10 ?mol/L potentiated the inhibited current to(127?9)% of its original value.Coapplication of Zn~(2+)(10 ?mol/L) potentiated ??-me ATP-induced currents to(146?5)% of the control.Zn~(2+)(300 ?mol/L) had no effect on ?_(on) and ?_(off) of ATP-and ??-me ATP-induced(30 ?mol/L) currents in OTG neurons.Conclusion:(1) Zn~(2+) is an allosteric modulator of P2X_(2) and P2X_(2/3) receptors in SCG and NG neurons and can potentiate the currents they induced.(2)The predominant receptor subtypes in OTG appear to be homomeric P2X_(2/3) and a little P2X_(2).Zn~(2+) has an inhibitory effect on the ATP-induced currents in OTG neurons,suggesting some novel members of the P2X purinoceptor exist in these neurons.

EFFECTS OF Zn~(2+) ON THE NEUROMUSCULAR TRANSMISSION / 西安交通大学学报(医学版)

Experiments were carried out on the isolatedrat phrenic nerve diaphragm preparations and chickbiventer cervicis preparations. Zn~(2+) at cumulativeconcentration inhibited muscle contractile responseto indirect stimulation without affecting the con-ductivity of nerve. The inhibiting. action of Zn~(2+) onthe muscle contractile response to indirect stimula-tion was stronger than that on contractile responseto direct stimulation. Zn~(2+) did not affect the Achsensitivity of the chick biventer cervicis muscleThe effects of Zn~(2+) on neuromuscular transmis-sion were antagonized by Ca~(2+) and L-cystein.