Methionine adenosyltransferase Ⅱ（MAT Ⅱ） is a key enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine （SAMe） from L-methionine and ATE Normal resting T lymphocytes have minimal MAT ...Methionine adenosyltransferase Ⅱ（MAT Ⅱ） is a key enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine （SAMe） from L-methionine and ATE Normal resting T lymphocytes have minimal MAT Ⅱ activity, whereas activated proliferating T lymphocytes and transformed T leukemic cells show significantly enhanced MAT Ⅱ activity. This work was carried out to examine the role of MAT Ⅱ activity and SAMe biosynthesis in the survival of leukemic T cells. Inhibition of MAT Ⅱ and the resultant decrease in SAMe levels enhanced expression of FasL mRNA and protein, and induced DISC （Death Inducing Signaling Complex） formation with FADD （Fasassociated Death Domain） and procaspase-8 recruitment, as well as concomitant increase in caspase-8 activation and decrease in c-FLIPs levels. Fas-initiated signaling induced by MAT Ⅱ inhibition was observed to link to the mitochondrial pathway via Bid cleavage and to ultimately lead to increased caspase-3 activation and DNA fragmentation in these cells. Furthermore, blocking MAT 2A mRNA expression, which encodes the catalytic subunits of MAT Ⅱ, using a small-interfering RNA approach enhanced FasL expression and cell death, validating the essential nature of MAT Ⅱ activity in the survival of T leukemic cells.展开更多
It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis ...It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways ofapoptotic cell death induction： extrin- sic signaling through death receptors that leads to the formation of the death-inducing signaling complex （DISC）, and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.展开更多
目的:观察血清Wnt1诱导信号通路蛋白1(Wnt1-inducible-signaling pathway protein 1,WISP1)水平在绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者中的变化,并分析其与骨密度(bone mineral density,BMD)各项骨代谢指标的相关性...目的:观察血清Wnt1诱导信号通路蛋白1(Wnt1-inducible-signaling pathway protein 1,WISP1)水平在绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者中的变化,并分析其与骨密度(bone mineral density,BMD)各项骨代谢指标的相关性,探索WISP1在PMOP发生发展中的作用。方法:选取2020年5月─2022年8月在苏州大学附属第一医院健康管理中心进行健康体检的绝经后女性共148例,利用双能X线吸收仪(dual-energy X-ray absorptiometry,DXA)骨密度仪测量腰椎骨密度,根据不同骨量分为骨量正常组(T值≥-1.0),骨量减少组(-2.5<T值<-1.0),骨质疏松组(T值≤-2.5),分别采集临床基本资料,测定骨代谢指标及血清WISP1质量浓度,经SPSS软件进行统计处理。结果:骨质疏松组及骨量减少组的血清WISP1质量浓度均显著高于骨量正常组(均P<0.05)。血清WISP1水平与成骨标志物碱性磷酸酶、总Ⅰ型前胶原氨基端肽密切相关。结论:WISP1可能通过刺激成骨反应参与PMOP的病理生理过程。展开更多
文摘Methionine adenosyltransferase Ⅱ（MAT Ⅱ） is a key enzyme in cellular metabolism and catalyzes the formation of S-adenosylmethionine （SAMe） from L-methionine and ATE Normal resting T lymphocytes have minimal MAT Ⅱ activity, whereas activated proliferating T lymphocytes and transformed T leukemic cells show significantly enhanced MAT Ⅱ activity. This work was carried out to examine the role of MAT Ⅱ activity and SAMe biosynthesis in the survival of leukemic T cells. Inhibition of MAT Ⅱ and the resultant decrease in SAMe levels enhanced expression of FasL mRNA and protein, and induced DISC （Death Inducing Signaling Complex） formation with FADD （Fasassociated Death Domain） and procaspase-8 recruitment, as well as concomitant increase in caspase-8 activation and decrease in c-FLIPs levels. Fas-initiated signaling induced by MAT Ⅱ inhibition was observed to link to the mitochondrial pathway via Bid cleavage and to ultimately lead to increased caspase-3 activation and DNA fragmentation in these cells. Furthermore, blocking MAT 2A mRNA expression, which encodes the catalytic subunits of MAT Ⅱ, using a small-interfering RNA approach enhanced FasL expression and cell death, validating the essential nature of MAT Ⅱ activity in the survival of T leukemic cells.
文摘It has been almost three decades since the term ＂apoptosis＂ was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways ofapoptotic cell death induction： extrin- sic signaling through death receptors that leads to the formation of the death-inducing signaling complex （DISC）, and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.
文摘目的:观察血清Wnt1诱导信号通路蛋白1(Wnt1-inducible-signaling pathway protein 1,WISP1)水平在绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者中的变化,并分析其与骨密度(bone mineral density,BMD)各项骨代谢指标的相关性,探索WISP1在PMOP发生发展中的作用。方法:选取2020年5月─2022年8月在苏州大学附属第一医院健康管理中心进行健康体检的绝经后女性共148例,利用双能X线吸收仪(dual-energy X-ray absorptiometry,DXA)骨密度仪测量腰椎骨密度,根据不同骨量分为骨量正常组(T值≥-1.0),骨量减少组(-2.5<T值<-1.0),骨质疏松组(T值≤-2.5),分别采集临床基本资料,测定骨代谢指标及血清WISP1质量浓度,经SPSS软件进行统计处理。结果:骨质疏松组及骨量减少组的血清WISP1质量浓度均显著高于骨量正常组(均P<0.05)。血清WISP1水平与成骨标志物碱性磷酸酶、总Ⅰ型前胶原氨基端肽密切相关。结论:WISP1可能通过刺激成骨反应参与PMOP的病理生理过程。
