| Apoptosis is an active programmed cell death, and through which harmful, superfluous and senescence cells can be wiped off to keep body normal and healthy. Data have shown the emergence and development of tumor is close related to free and inhibition of apoptosis. To a certain extent, the therapy strategy for tumor is mostly aimed to induce apoptosis. In the representative therapy with radiation and daunorobicin, ceramide content increased. Many papers focused on the regulation of apoptosis by sphingolipids and the regulation of apoptosis mechanism is an area of active investigation since ceramide was confirmed as a lipid second messenger in 1994, but much information is needed to uncover the action mechanism. On the other hand, peroxisome proliferator-activated receptor have shown to play an important role in apoptosis modulation, and since PPAR was thought to be a critical link of lipid metabolism, gene expression and carcinogenesis, so this paper is to study the relationship of sphingolipids and PPAR and the effects on the modulation of apoptosis, from a new point of view. The major results are shown as follows.Firstly, the study on the apoptosis modulation by sphingolipids was done. We focused on the factors, such as treating time, caspases, MAPK signaling, cell cyclin dependent kinases, nuclear factondB (NFkB) on the apoptosis modulation by ceramide using Bel7402 cell line as a model. And the following results were obtained: (1) Inhibition of cell proliferation and induction of apoptosis was observed when cells were treated with ceramides, and at the same time, the percentage of cells in the S phase was found to decrease significantly; (2) The expression of CDK7 significantly decreased when cells were treated by ceramide, which showed CDK7 play a very important role in the inhibition of cell proliferation; (3) While ceramide can inhibit cell growth and induce apoptosis, two different pathways existed to induce apoptosis when cells were treated with ceramide for different time. A Short-time ceramide treatment-induced cell death was not associated with the typical apoptotic phenotypes, but associated with the p38 activation in caspase -independent pathway. B Long-time ceramide treatment-induced cell death was characterized with typical apoptotic phenotypes, but not the p38 activation in caspase-dependent pathway. And the caspase-independent mechanism was also implicated in ceramide-induced apoptosis occurred in the later period of the treatment. (4) On the other hand, during the apoptosis induction, ceramide was found to activate the nuclear factor kB (NFkB) with the altered distribution in the cell, although little jnformation was kown about the modulation and the significance.Secondly, the investigation on the regulation of apoptosis by PPAR was made. Effects of the impact factors, such as caspases, cell cycle distribution regulation and transcriptional activity of PPARy on the apoptosis modulation using PPARr pharmacological ligands were focused. The results were shown as follows. (1) Ciglitazone, one PPARy ligand, can inhibit cell proliferaion and induce apoptosis, associated with cell cycle characterized with G0/G1 arrest; (2) Ciglitazone-induced apoptosis was incaspase-dependent pathway. (3) The transcriptional activity of PPARγ was stimulated by treatment with PPARγ ligands (ciglitazone, troglitazone and clofibrate), and the activity was inhibited when pre-treatment with GW9662; (4) The induction of apoptosis by ciglitazone was reversed by co-treatment with GW9662.Lastly, investigation on the relationship of sphingolipids and PPAR was carried, and further studies were aimed to uncover the modulation mechanism of apoptosis using the conclusion. The following results were obtained. (1) While much was unclear to uncover the specific modulation mechanisms, C2, C8-ceramides were shown to down-regulate the expression of PPARγ on the mRNA and protein level in a dose-dependent pathway, (2) and GW9662 recovered the decrease effect when co-treatment with ceramides; (3) C2-, C8-ceramide...
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