共查询到12条相似文献,搜索用时 15 毫秒
1.
Wang SH Shih YL Ko WC Wei YH Shih CM 《Cellular and molecular life sciences : CMLS》2008,65(22):3640-3652
The cytotoxicity of cadmium (Cd) induced autophagy and apoptosis in MES-13 cells was determined by flow cytometry. Autophagy
was also assessed by formation of autophagosomes and processing of LC3. Pharmacological inhibition of autophagy resulted in
increased of cell viability, suggesting autophagy plays a role in cell death in Cd-treated mesangial cells. Cd also induced
a rapid elevation in cytosolic calcium ([Ca2+]i ), and modulation of [Ca2+]i via treatment with IP
3R inhibitor or knockdown of calcineurin resulted in a change in the proportion of cell death, suggesting that the release
of calcium from the ER plays a crucial role in Cd-induced cell death. Inhibition of Cd-induced ERK activation by PD 98059
suppressed Cd-induced autophagy, and BAPTA-AM eliminated activation of ERK. BAPTA-AM also inhibited Cd-induced mitochondrial
depolarization and activation of caspases. These findings demonstrated that Cd induces both autophagy and apoptosis through
elevation of [Ca2+]i, followed by Ca2+-ERK and Ca2+-mitochondria-caspase signaling pathways.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 05 July 2008; received after revision 25 August 2008; accepted 17 September 2008 相似文献
2.
Molecular genetic analysis of the calcineurin signaling pathways 总被引:3,自引:0,他引:3
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N-acetylglucosaminyltransferase V modifies the signaling pathway of epidermal growth factor receptor 总被引:3,自引:0,他引:3
Guo P Wang QY Guo HB Shen ZH Chen HL 《Cellular and molecular life sciences : CMLS》2004,61(14):1795-1804
Transfection of sense cDNA of N-acetylglucosamyltransferase V (GnTV-S) into human H7721 hepatocarcinoma cells
resulted in an increase in the N-acetylglucosamine1,6mannose1,3- branch (GnT-V product) on the
N-glycans of epidermal growth factor (EGF) receptor (EGFR), and promotion of its EGF binding and tyrosine
autophosphorylation, but showed little effect on the expression of EGFR protein. The phosphorylation at T308,
S473 and tyrosine residue(s) and the activity of protein kinase B (Akt/PKB) as well as the phosphorylation of
p42/44 mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) before and after EGF stimulation were
concomitantly increased. Conversely, in the antisense GnT-V (GnTV-AS)-transfected H7721 cells, all the results
were the reverse of those with GnTV-S-transfected cells. After the cells were treated with 1-deoxymannojirimycin,
an inhibitor of N-glycan processing at high mannose, or antibody against the extracellular glycan domain of EGFR,
the differences in PKB activity, p42/44 MAPK and MEK phosphorylation among GnTV-S-, GnTV-AS- and mock-transfected
cells were significantly attenuated. These findings indicate that the altered expression of GnT-V will change the
glycan structure and function of EGFR, which may modify downstream signal transduction.Received 24 March 2004; received after revision 1 May 2004; accepted 25 May 2004 相似文献
6.
Intraluminal injections (15 l) of either concanavalin A (125 g) or ionophore A 23187 (0.01 mol) induced a decidual cell reaction (DCR) in the uterus of day 4.5 pseudopregnant mice. However, when these agents were administered in different combinations with each other or with CaCl2 (15 mol) and phorbol-12-myristate-13-acetate (1.6 nmol), interacting effects occurred to either enhance or inhibit each of the others' independent deciduogenic capacities. The results suggest that the polyphosphatidylinositol pathway and Ca2+ are involved in the induction of the DCR in mice with complex interactions occurring between the active components of the pathway to modulate the outcome of the transformation process. 相似文献
7.
C. J. Duncan 《Cellular and molecular life sciences : CMLS》1990,46(1):41-48
Summary The O2– and Ca2+-paradoxes have a number of features in common and it is suggested that release of cytosolic proteins in both paradoxes is initiated by the activation of a sarcolemma NAD(P)H dehydrogenase which can generate a transmembrane flow of H+ and e– and also oxygen radicals or recox cycling which damage ion channels and membrane proteins (phase I). Entry of Ca2+ through the damaged ion channels then exacerbates the damage by further activating this system, either directly or indirectly, and the redox cycling and/or oxygen radicals cause further damage to integral and cytoskeletal proteins of the sarcolemma resulting in microdamage to the integrity of the membrane (phase II) and the consequent release or exocytosis of cytoplasmic proteins and, under specialised condition, the blebbing of the sarcolemma. The system may be primed either by removal of extracellular Ca2+ or by raising [Ca2+]i by a variety of measures, these two actions being synergistic. The system is initially activated in the Ca2+-paradox by the membrane perturbation associated with removal of extracellular Ca2+; prolonged anoxia in the metabolically active cardiac muscle causes a depletion of the ATP supply, particularly in the absence of glucose, and hence a rise in [Ca2+]i in phase I of the oxygen paradox with the consequent activation of the NAD(P)H oxidase at the sarcolemma. Oxygen radicals are probably generated in both paradoxes and may have a partial role in the genesis of damage, but are not essential in the Ca2+-paradox which continues under anoxia. Massive entry of Ca2+ also activates an intracellularly localised dehydrogenase (probably at the SR) which produces myofilament damage by redox cycling. 相似文献
8.
Differential insult-dependent recruitment of the intrinsic mitochondrial pathway during neuronal programmed cell death 总被引:1,自引:1,他引:0
Diwakarla S Nagley P Hughes ML Chen B Beart PM 《Cellular and molecular life sciences : CMLS》2009,66(1):156-172
Programmed cell death contributes to neurological diseases and may involve mitochondrial dysfunction with redistribution of
apoptogenic proteins. We examined neuronal death to elucidate whether the intrinsic mitochondrial pathway and the crosstalk
between caspase-dependent/-independent injury was differentially recruited by stressors implicated in neurodegeneration. After
exposure of cultured cerebellar granule cells to various insults, the progression of injury was correlated with mitochondrial
involvement, including the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Injury
occurred across a continuum from Bax- and caspase-dependent (trophic- factor withdrawal) to Bax-independent, calpain-dependent
(excitotoxicity) injury. Trophic-factor withdrawal produced classical recruitment of the intrinsic pathway with activation
of caspase-3 and redistribution of cytochrome c, whereas excitotoxicity induced early redistribution of AIF and HtrA2/Omi,
elevation of intracellular calcium and mitochondrial depolarization. Patterns of engagement of neuronal programmed cell death
and the redistribution of mitochondrial IMS proteins were canonical, reflecting differential insult-dependencies.
Received 14 August 2008; received after revision 02 October 2008; accepted 23 October 2008 相似文献
9.
To understand the role of calcium ions in thigmotaxis inParamecium caudatum, the effects of caffeine, ruthenium red and lanthanum (LaCl3) on thigmotaxis were examined. Thigmotaxis in the CNR mutant, which lacks voltage-dependent Ca2+-channels in the ciliary membrane, was also examined. Ruthenium red and LaCl3 suppressed thigmotaxis inP. caudatum, while caffeine enhanced it. The CNR mutant showed hardly any thigmotaxis. It can be thought that an increase in Ca2+ influx and the intraciliary concentration of Ca2+ ions induces thigmotaxis inParamecium. 相似文献
10.
Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways 总被引:1,自引:0,他引:1
M. Y. Lee S. H. Lee J. H. Park H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(8):1467-1478
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal,
although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [3H]-thymidine incorporation as well as cyclin expression and decreased p27kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2.
In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced
cyclin expression and [3H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced
phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was
decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src,
caveolin-1 Akt, and mTOR signaling pathways.
Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009 相似文献
11.
Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease 总被引:5,自引:0,他引:5
The DSCR1 (Adapt78) gene1 is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic
expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac
hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein
phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506,
affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may
also play a role in a variety of human diseases.
1Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final
approval must await agreement from a majority of researchers in the field.
Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005 相似文献
12.
Averna M De Tullio R Capini P Salamino F Pontremoli S Melloni E 《Cellular and molecular life sciences : CMLS》2003,60(12):2669-2678
The amount of calpastatin directly available in cytosol is under the control of [Ca2+] and [cyclic AMP]. Prolonged calpain activation also promotes degradation of calpastatin. The fluctuation of calpastatin concentration in cell soluble fraction is accompanied by an initial decrease in calpastatin gene expression, followed by a fivefold increase in its expression when the inhibitor protein is degraded. This process can be conceptualized as a mechanism to regulate calpastatin availability in the cell. This conclusion is supported by the fact that calpain, the other component of this proteolytic system, undergoes changes in its levels of expression in a much more limited manner. Furthermore, this process can be observed both in cells exposed to different natural stimuli, or in other cell lines. Modification of calpastatin gene expression might represent a new tool for the in vivo control of the regulatory machinery required for the modulation of Ca2+-dependent proteolysis.Received 18 July 2003; received after revision 3 September 2003; accepted 23 September 2003 相似文献