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1.
Short term regulation of hepatic cholesterol ester hydrolase by reversible phosphorylation is described. Two different kinase
systems seem to be involved in this regulation. The addition of ATP, cyclic AMP and Mg2+ to rat liver 104,000× g supernatant (S104) produced a 100–140% increase in cholesterol ester hydrolase activity. This stimulation
was abolished when protein kinase inhibitor was added prior to the addition of ATP, cyclic AMP and Mg2+. Cholesterol ester hydrolase activity was also stimulated when calcium ions, phosphatidylserine, and diolein were added to
S104 along with ATP and Mg2+. Diolein in this reaction could be substituted by phorbol 12-myristate 13-acetate. Preincubation of S104 with alkaline phosphatase
resulted in a deactivation of cholesterol ester hydrolase. The addition of increasing concentrations of Mg2+ to S104 produced increasing inhibition of cholesterol ester hydrolase activity, and this effect was blocked by NaF.
It is suggested that rat liver cholesterol ester hydrolase is activated by cyclic AMP dependent protein kinase and protein
kinase C. Deactivation is accomplished by dephosphorylation catalyzed by a phosphoprotein phosphatase, dependent on Mg2+.
This work was presented at the Twenty-Third Southeastern Regional Lipid Conference, held October 26–28, in Cashiers, North
Carolina. 相似文献
2.
In the presence of hydroxylamine or ascorbic acid, the inhibitory effects of Cu2+ on lysosomal acid cholesteryl ester hydrolase (acid CEH) partially purified from rat liver were studied.
Hydroxylamine stimulated the inhibition of acid CEH activity by Cu2+ but not that by Zn2+, Fe2+, Co2+, Mn2+, Ca2+, Mg2+ and Hg2+. This Cu2+-dependent inhibition of acid cholesterol ester hydrolase (CEH) activity was completely prevented by ethylenediamine tetraacetic
acid (EDTA), EGTA and o-phenanthroline, a chelator with a stability constant for Cu2+, and also by sulfhydryl agents and cytoplasmic reducing agents such as cysteine, glutathione and mercaptoethanol. In addition,
the stimulative effects of hydroxylamine on Cu2+-dependent inhibition were maintained even after preincubation of Cu2+ with hydroxylamine.
On the other hand, ascorbic acid was found to replace the stimulation by hydroxylamine of the Cu2+-dependent inhibition of acid CEH activity but the effects of ascorbic acid progressively became smaller with prolongation
of the preincubation time. Moreover, addition of chemical radical scavengers to the reaction mixture did not prevent the Cu2+-dependent inhibition of acid CEH activity in the presence of ascorbic acid. These results suggest that Cu2+ causes inhibition of lysosomal acid CEH activity through the formation of Cu1+ in a reductive medium. 相似文献
3.
Kathleen M. Botham 《Lipids》1991,26(11):901-906
An acid cholesteryl ester hydrolase activity associated with a fraction containing mitochondria and lysosomes from rat lactating
mammary glands was found to have a pH optimum of 5.0. Its sedimentation pattern was closely related to that of the lysosomal
enzyme markers acid phosphatase and β-glucuronidase, suggesting that the activity is associated with the lysosomes. The enzyme
was strongly inhibited by Cu2+, but was inhibited little by other divalent metal ions. Acid cholesteryl ester hydrolase activity was almost completely abolished
byp-hydroxymercuribenzoate, but this effect was reversed in the presence of an equimolar concentration of reduced glutathione
(GSH), indicating that the enzyme requires free sulfhydryl groups for activity. These properties are similar to those of acid,
lysosomal cholesteryl ester hydrolases found in other tissues. Acid cholesteryl ester hydrolase activity was 8–14 fold higher
in mammary tissue from lactating as compared to virgin rats. Neutral cholesteryl ester hydrolase activities associated with
the microsomal and cytosolic subcellular fractions were also increased in lactating glands, but to a lesser extent. In addition,
a 2-fold increase in the activities of both the acid and microsomal neutral enzymes was seen during the first few days of
lactation, while the cytosolic neutral activity remained constant. These results suggest that mammary gland cholesteryl ester
hydrolases have a role in the regulation of cholesterol metabolism in mammary cells, and in the provision of cholesterol for
secretion into milk. 相似文献
4.
Cholesterol esterification by acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) has been studied in microsomes isolated
from the mammary glands of rats in late pregnancy, in early and mid-lactation, and following premature weaning. The mammary
glands were freeze-clamped and the microsomes prepared in the presence of phosphatase inhibitors to preserve the phosphorylation
status of the enzyme. Optimal conditions were established for the assay of enzyme activity in the presence of endogenous cholesterol.
Supplementation of the microsomes with exogenous cholesterol as a dispersion in Triton WR-1339 was shown to lead to an increase
in enzyme activity. Incubation of microsomes with MgATP led to an increase in ACAT activity which could be reversed by treatment
of the microsomes with a phosphoprotein phosphatase preparation from rat liver. The results suggested that ACAT activity in
the mammary gland was activated by phosphorylation in a similar way to that observed for the hepatic enzyme. The mammary glands
from pregnant animals contained a higher level of ACAT activity than did the glands of the lactating animals and this correlated
with the higher cholesteryl ester content of the pregnant glands. The highest level of ACAT activity was found in the weaned
animals but the cholesteryl ester content of the microsomes was lower than expected. The influence of progesterone levels
and changes in feeding patterns during gestation were considered as factors in these variations in ACAT activity. 相似文献
5.
Experimental Mg2+ deficiency was induced in a group of rats by feeding them a Mg2+-deficient diet for 23 days. They were pair-fed to compare with a control group of rats fed a Mg2+-sufficient diet. In the Mg2+-deficient group the plasma total cholesterol and triglyceride levels were increased while HDL-cholesterol was decreased.
In the Mg2+-deficient group the plasma level of thiobarbituric acid reacting substances (TBARS) used as a measure for lipid peroxidation
was increased. The increase was attributed to the increased cytosolic Ca2+ in Mg2+-deficiency which can cause: 1) increase of hydro and endoperoxide levels as a consequence of the increase of arachidonic
acid release and eicosanoid synthesis in Mg2+-deficiency, and 2) inhibition of the mitochondrial respiratory activity and activation of Ca2+-dependent proteases which may activate the conversion of xanthine dehydrogenase to xanthine oxidase which generates active
O2 species. In the Mg2+-deficient group, the fatty acid composition of the liver microsomes indicated a slower rate of conversion of linoleic acid
to arachidonic acid which was consistent with the decrease of Δ6 desaturase activity in liver microsomes of Mg2+-deficient rats as measuredin vitro. The decrease of Δ6 desaturase activity was attributed to the lower concentration of actual enzyme molecules as a result
of the decreased rate of protein synthesis in Mg2+-deficiency. The possible effects of the increased catecholamine release in Mg2+-deficiency are discussed. 相似文献
6.
Cholesterol ester hydrolase activity has been studied in mammary glands of rats. Subcellular fractionation of the glands obtained
in mid-lactation indicated that around 80% of the recovered activity was associated with particulate fractions. Two distinct
cholesterol ester hydrolase activities were identified, one with an optimum pH of 7.5–9.0 and the second (approximately 5%
of the total activity) with a more acidic pH optimum. Although the neutral cholesterol ester hydrolase had some properties
in common with the lipoprotein lipase in mammary tissue, it was shown to be a separate entity by several criteria. Its activity
could be increased following treatment with Mg-ATP and cAMP-dependent protein kinase, suggesting identity with the hormone
sensitive lipase of adipose tissue. The cholesterol ester hydrolase activity in mammary glands just after parturition was
greater than in glands obtained either from late-pregnant or midlactating animals. The subcellular distribution of the neutral
cholesterol ester hydrolase suggested that it may have a different function to the neutral cholesterol ester hydrolase of
adrenals and other tissues. Nevertheless the fact that the activity of the enzyme can be modulated by cAMP-dependent protein
kinase suggests the possibility that hormonal control of this enzyme may be involved in the regulation of cholesterol metabolism
in the mammary gland. 相似文献
7.
Anastasiia Bohush Wiesawa Leniak Serge Weis Anna Filipek 《International journal of molecular sciences》2021,22(6)
Parkinson’s disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca2+ as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca2+ homeostasis and dysfunction of Ca2+ signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca2+ level. The best known and studied Ca2+ sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca2+ with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD. 相似文献
8.
The specific activity of the microsomal Δ12-desaturase system, which transforms oleic acid into linoleic acid, was about 16
pmol/min/mg protein. However, most of the total activity was nonsedimentable even after a 200000×g centrifugation for 100 min. The study of various physicochemical parameters showed that this enzymatic complex, functioning
optimally between pH 7 and 8, had low thermal stability. Ca2+, which may cause an aggregation of the microsomes, and Hg2+ completely inhibited the activity, whereas Mg2+, Mn2+, and Zn2+ were activators. The Δ12-desaturase system was relatively specific toward oleic acid, though isomers of this fatty acid also
had an action, either as substrates or as competitive inhibitors, on the activity of the system. The study of the effect of
the exogenous oleoyl-CoA and elaidoyl-CoA on the specific activity of the Δ12-desaturase system showed a preference toward
oleoyl-CoA. 相似文献
9.
Diacylglycerol lipase (EC 3.1.1.3) was purified from bovine brain microsomes using multiple column chromatographic techniques.
The purified enzyme migrates as a single band on SDS-PAGE and has an apparent molecular weight of 27 kDa. Substrate specificity
experiments using mixed molecular species of 1,2-diacyl-sn-glycerols indicate that low concentrations of Ca2+ and Mg2+ have no direct effect on enzymic activity and 1,2-diacyl-sn-glycerols are the preferred substrate over 1,3-diacyl-sn-glycerols. The enzyme hydrolyzes stearate in preference to palmitate from the sn-1 position of 1,2-diacyl-sn-glycerols. 1-O-Alkyl-2-acyl-sn-glycerols are not a substrate for the purified enzyme. The native enzyme had a V
max value of 616 nmol/min mg protein. Phosphorylation by cAMP-dependent protein kinase resulted in a threefold increase in catalytic
throughput (V
max = 1,900 nmol/min mg protein). The substrate specificity and catalytic properties of the bovine brain diacylglycerol lipase
suggest that diacylglycerol lipase may regulate protein kinase C activity and 2-arachidonoyl-sn-glycerol levels by rapidly altering the intracellular concentration of diacylglycerols. 相似文献
10.
Incubation of Caco-2 cells, a human intestinal cell line, with 25-hydroxycholesterol (25-HOC) markedly enhanced cellular cholesteryl
ester formation determined by incorporation of [14C]oleic acid into intracellular cholesteryl [14C]oleate. The stimulation by 25-HOC of cholesteryl ester formation was suppressed by staurosporine, a kinase inhibitor, but
not by cycloheximide or actinomycin D. The specific activity of microsomal acyl-coenzyme A:cholesterol acyltransferase (ACAT)
increased two-fold in cells treated with 10 μM 25-HOC for 5 h. ACAT activity decreased when microsomes were incubated without
sodium fluoride, a phosphatase inhibitor, but the decrease in ACAT activity in cells stimulated with 25-HOC was more pronounced.
The results suggest that protein phosphorylation may be involved in the stimulation of cholesteryl ester formation by 25-HOC
in Caco-2 cells. 相似文献
11.
We investigate the messenger role of calcium ions implicated in the regulation of wave-like bending dynamics of flagella. The emphasis is on microtubules of flagellar axoneme serving as nonlinear transmission lines for bell-shaped spikes of calcium ions. The calcium sensitive proteins, such as calmodulin, exhibit activation dependence on the spike train frequency and amplitude. Here, we analyze a Ca2+ decoding module IDA-I1 whose activity is controlled by Ca2+ activated kinase. We find that trains of Ca2+ spikes are advantageous compared to a constant rise in Ca2+ concentration as being more efficient and much less prone to noisy fluctuations. 相似文献
12.
Johann Hofmann Florian Ueberall Lydia Posch Karl Maly Dieter B. J. Herrmann Hans Grunicke 《Lipids》1989,24(4):312-317
The new phospholipid analogue 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine inhibits the phospholipid-calcium-dependent
protein kinase, partially purified from Walker carcinoma cells with a Ki value of 0.56 μM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating
that the depression of Ca2+-phospholipid-dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the
inhibition of cell proliferation by 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine in Walker cells exhibits
a close correlation to the dose effect curve for the depression of Ca2+-phospholipid-dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that
the growth inhibitory activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine correlates with the inhibition
of Ca2+-phospholipid-dependent protein kinase. The antiproliferative activity of 3-hexadecylmercapto-2-methoxymethyl-propyl-1-phosphocholine
is synergistically enhanced bycis-diamminedichloroplatinum(II). 相似文献
13.
Some properties of the pure, soluble phospholipase D (phosphatidycholine phosphatido hydrolase, EC 3.1.4.4) interactions with
phosphatidyl choline (1,2 diacyl-sn-glycerol-3-phosphoryl choline) in a system also containing dodecylsulfate and Ca2+ ions were studied. Concentrations of Ca2+ greater than 50 mM were necessary both for activity and adsorption of the enzyme to the “supersubstrate.” Ethylenediamine
tetraacetic acid caused inhibition of activity, greater than one would expect from its chelating capacity. A nonlinear increase
in activity with the increase of enzyme protein was observed, suggesting a subunit aggregation into a higher mol wt protein,
catalytically more active. Upon centrifugation of the supersubstrate-enzyme complex at 4.5×105
g·min at 30 C, most of the substrate molecules sedimented regardless of the pH. The reverse was true when centrifugation was
done at 1 C. Phospholipase D hydrolyzed phosphatidylcholine molecules present in the supersubstrate at temperatures around
0 C at a rate 1/5 that of a maximal value measured at 30C. The Arrhenius plot was linear in the range from 0 to 30 C, and
at that temperature the curve broke with a smaller slope. Activation energy of 9.1 Kcal/mol, below 30 C, was calculated. Adsorption
of the enzyme to the sedimentable supersubstrate occurred at pH 8.0, regardless of temperature. At pH 5.6, a considerable
portion of phosphatidylcholine was degraded at 30 C, thus minimizing the capacity of the supersubstrate to adsorb the enzyme.
Although Mg2+ could replace Ca2+ in the formation of sedimentable supersubstrate, it neither assists in adsorption of the enzyme nor in activation of the
phosphatidylcholine hydrolysis. 相似文献
14.
Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This gene contains an ORF of 1488 bp that encodes a 495 amino acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and humans respectively. The full-length of PxCNA and its catalytic domain (CNA1–341, defined as PxCNα) were both expressed in Escherichia coli. Purified recombinant PxCNA displayed no phosphatase activity, whereas recombinant PxCNα showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66 S−1 against pNPP. It could be activated at different degrees by Mn2+, Ni2+, Mg2+, and Ca2+. The optimum reaction pH was about 7.5 and the optimum reaction temperature was around 45 °C. An in vitro inhibition assay showed that okadaic acid (OA) and cantharidin (CTD) competitively inhibited recombinant PxCNα activity with the IC50 values of 8.95 μM and 77.64 μM, respectively. However, unlike previous reports, pyrethroid insecticides were unable to inhibit recombinant PxCNα, indicating that the P. xylostella calcineurin appears not to be sensitive to class II pyrethroid insecticides. 相似文献
15.
Yi-Chieh Hung Yi-Hsiu Kuo Pei-Wen Hsieh Ting-Yang Hsieh Jinn-Rung Kuo Su-Jane Wang 《International journal of molecular sciences》2021,22(21)
The glutamatergic neurotransmitter system has received substantial attention in research on the pathophysiology and treatment of neurological disorders. The study investigated the effect of the polyphenolic compound chlorogenic acid (CGA) on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). CGA inhibited 4-aminopyridine (4-AP)-induced glutamate release from synaptosomes. This inhibition was prevented in the absence of extracellular Ca2+ and was associated with the inhibition of 4-AP-induced elevation of Ca2+ but was not attributed to changes in synaptosomal membrane potential. In line with evidence observed through molecular docking, CGA did not inhibit glutamate release in the presence of P/Q-type Ca2+ channel inhibitors; therefore, CGA-induced inhibition of glutamate release may be mediated by P/Q-type Ca2+ channels. CGA-induced inhibition of glutamate release was also diminished by the calmodulin and Ca2+/calmodilin-dependent kinase II (CaMKII) inhibitors, and CGA reduced the phosphorylation of CaMKII and its substrate, synapsin I. Furthermore, pretreatment with intraperitoneal CGA injection attenuated the glutamate increment and neuronal damage in the rat cortex that were induced by kainic acid administration. These results indicate that CGA inhibits glutamate release from cortical synaptosomes by suppressing P/Q-type Ca2+ channels and CaMKII/synapsin I pathways, thereby preventing excitotoxic damage to cortical neurons. 相似文献
16.
Preparation of aqueous soluble polyamides from renewable succinic acid and citric acid as a new approach to design bio‐inspired polymers
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A novel type of aqueous soluble polyamides were prepared as renewable substitutes for ecologically benign poly(aspartic acid) by polymerization of succinic acid ester and hexamethylene diamine in the presence of citric acid ester. The copolymerization resulted in the formation of poly(amide imide) intermediates, which were hydrolyzed to aqueous solutions of polyamides. The hydrolyzed products were confirmed to be copolymers of succinamide and citramide with COOH side chains, similar to poly(aspartic acid). The polyamides showed strong chelating abilities to Ca2+ and Pb2+ metals, comparable to poly(aspartic acid). Interestingly, they also demonstrated antifreeze activities in water by reducing the ice fractions. The polyamides represent a new class of metal chelators and antifreeze protein mimics derived from succinamide and citramide. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39807. 相似文献
17.
We characterized phospholipase A2 (PLA2) activity in isolated rabbit ventricular myocytes with respect to subcellular distribution, substrate specificity, and Ca2+ dependency. Membrane-associated PLA2 was found to be an order of magnitude greater than cytosolic PLA2. Ventricular myocyte PLA2 activity was enhanced following protease-activated receptor stimulation with thrombin and was found to be largely Ca2+-independent and selective for phospholipid substrates containing arachidonic acid at the sn-2 position. Immunoblot analysis using an antibody to cytosolic Ca2+-independent PLA2 from Chinese hamster ovary cells recognized a membrane-associated protein with a molecular mass of approximately 80 kDa;
however, differences in pH optima, response to inhibitors, and substrate selectivity of membrane-associated and cytosolic
PLA2 activity suggest the presence of multiple Ca2+-independent PLA2. Pretreatment with bromoenol lactone, a specific inhibitor of Ca2+-independent PLA2, significantly attenuated membrane-associated and cytosolic PLA2 in unstimulated and thrombin-stimulated myocytes. Pretreatment with methyl arachidonyl fluorophosphonate, mepacrine, or dibucaine
had no significant effect on PLA2 activity under all conditions tested. Ventricular myocyte PLA2 activity was significantly inhibited by ATP, GTP, and their nonhydrolyzable analogs and was regulated by protein kinase C
activity. These studies demonstrate the presence of one or more unique membrane-associated Ca2+-independent PLA2 in isolated ventricular myocytes that exhibit a preference for phospholipids with arachidonate at the sn-2 position and that are activated by thrombin stimulation. 相似文献
18.
The direct activation of sterol ester hydrolase (E.C. 3.1.1.13) in homogenates of bovine corpus luteum by N6O2′·dibutyryl cyclic adenosine 3′∶5′-phosphate, (dibutyryl cAMP), adenosine triphosphate (ATP), and Mg2+ has been demonstrated. Variability in the extent of activation by the additions was minimized by homogenization of the tissue
in 5 mM Mg2+. Baseline sterol ester hydrolase activity was primarily associated with the 105,000 × g soluble fraction, and significant
activation of the enzyme preparation preincubated with dibutyryl cAMP, ATP and Mg2+ occurred within the first 15 min, prior to addition of substrate. A requirement for protein kinase in the system was demonstrated
by blocking the cofactor-dependent enzyme activation with commercial protein kinase inhibitor. 相似文献
19.
An extracellular lipase (EC 3.1.1.3) from Geotrichum marimum was purified 76-fold with 46% recovery using Octyl Sepharose 4 Fast Flow and Bio-Gel A 1.5 m chromatography. The purified
enzyme showed a prominent band on SDS-PAGE and a single band on native PAGE based on the activity staining. The molecular
mass of the lipase was estimated to be 62 kDa using SDSPAGE and Bio-Gel A chromatography, indicating that the lipase likely
functions as a monomer. The pl of the lipase was determined to be 4.54. The apparent V
max and K
m were 1000 μmol/min/mg protein and 11.5 mM, respectively, using olive oil emulsified with taurocholic acid as substrate. The
lipase demonstrated a pH optimum at pH 8.0 and a temperature optimum at 40°C. At 6 mM, Na+, K+, Ca2+, and Mg2+ stimulated activity, but Na+, and K+ at 500 mM and Fe2+ and Mn2+ at 6 mM reduced lipase activity. The anionic surfactant, taurocholic acid, and the zwitterionic surfactant, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate,
enhanced the activity at 0.1 mM. Other anionic surfactants such as SDS and sodium dioctyl sulfosuccinate, the cationic surfactants
methylbenzethonium bromide and cetyltriethylammonium bromide, and the nonionic surfactants Tween-20 and Triton X-100 inhibited
the lipase activity to different extents. The lipase was found to have a preference for TG containing cis double bonds in their FA side chains, and the reaction rate increased with an increasing number of double bonds in the side
chain. The lipase had a preference for ester bonds at the sn-1 and sn-3 positions over the ester bond at the sn-2 position. 相似文献
20.
Jesús Argueta Hctor Solís-Chagoyn Rosa Estrada-Reyes Luis A. Constantino-Jonapa Julin Oikawa-Sala Javier Velzquez-Moctezuma Gloria Benítez-King 《International journal of molecular sciences》2022,23(5)
Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca2+, CaM binds to CaM-dependent kinase II (CaMKII). The Ca2+-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca2+-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca2+-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca2+-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase. 相似文献