[目的]探讨鸡热休克蛋白8(heat shock protein family A member 8,HSPA8)的生物学特性及其在应激状态下胸腺中的表达模式。[方法]试验以固始鸡胸腺为材料,利用PCR技术扩增并克隆HSPA8基因CDS区,通过生物信息学方法分析其生物学特性和结...[目的]探讨鸡热休克蛋白8(heat shock protein family A member 8,HSPA8)的生物学特性及其在应激状态下胸腺中的表达模式。[方法]试验以固始鸡胸腺为材料,利用PCR技术扩增并克隆HSPA8基因CDS区,通过生物信息学方法分析其生物学特性和结构特点,并检测其在不同组织中的相对表达量。构建断喙应激和热应激模型,采用实时荧光定量PCR技术检测炎症因子和HSPA8基因在不同应激模型鸡胸腺中的表达情况。[结果]鸡HSPA8基因CDS区长度为1 941 bp,共编码氨基酸646个,与红原鸡基因序列相似性为98.92%;HSPA8基因核苷酸序列的系统发育树结果表明,固始鸡与火鸡亲缘关系最近,与哺乳动物次之,与低等鱼类亲缘关系最远;HSPA8蛋白属于酸性蛋白,稳定性和亲水性强,不属于分泌蛋白且无跨膜结构域,有多个磷酸化和糖基化修饰位点,主要在细胞核内发挥作用,具有2个保守性结构域,与DNAJC5、HSPB1、DNAJA1和GAK等蛋白存在相互作用;HSAP8基因在雏鸡各组织中广泛表达,其中在胰腺中表达量最高,在胸肌中表达量最低;应激模型评价结果发现,断喙应激和热应激导致鸡血清皮质酮、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等含量显著增加(P<0.05),T细胞亚群(CD3^(+))和免疫球蛋白G(IgG)含量有所降低;断喙应激模型鸡胸腺中IL-1β、IL-6、TNF-α和IL-8基因表达量在第1天显著升高(P<0.05),第5天显著降低(P<0.05);热应激模型鸡胸腺中IL-1β、IL-6、TNF-α和IL-8基因表达量显著升高(P<0.05);HSPA8基因在断喙后第1和3天胸腺中表达量显著升高(P<0.05),第5天显著降低(P<0.05);在持续热应激组中显著降低(P<0.05)。[结论]HSPA8基因参与鸡胸腺应激性免疫应答反应,可作为反映家禽是否处于应激性免疫抑制状态的可靠指标。以上结果为进一步研究HSPA8的免疫调控功能提供参考依据。展开更多
Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(no...Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.展开更多
The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates...The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.展开更多
文摘[目的]探讨鸡热休克蛋白8(heat shock protein family A member 8,HSPA8)的生物学特性及其在应激状态下胸腺中的表达模式。[方法]试验以固始鸡胸腺为材料,利用PCR技术扩增并克隆HSPA8基因CDS区,通过生物信息学方法分析其生物学特性和结构特点,并检测其在不同组织中的相对表达量。构建断喙应激和热应激模型,采用实时荧光定量PCR技术检测炎症因子和HSPA8基因在不同应激模型鸡胸腺中的表达情况。[结果]鸡HSPA8基因CDS区长度为1 941 bp,共编码氨基酸646个,与红原鸡基因序列相似性为98.92%;HSPA8基因核苷酸序列的系统发育树结果表明,固始鸡与火鸡亲缘关系最近,与哺乳动物次之,与低等鱼类亲缘关系最远;HSPA8蛋白属于酸性蛋白,稳定性和亲水性强,不属于分泌蛋白且无跨膜结构域,有多个磷酸化和糖基化修饰位点,主要在细胞核内发挥作用,具有2个保守性结构域,与DNAJC5、HSPB1、DNAJA1和GAK等蛋白存在相互作用;HSAP8基因在雏鸡各组织中广泛表达,其中在胰腺中表达量最高,在胸肌中表达量最低;应激模型评价结果发现,断喙应激和热应激导致鸡血清皮质酮、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等含量显著增加(P<0.05),T细胞亚群(CD3^(+))和免疫球蛋白G(IgG)含量有所降低;断喙应激模型鸡胸腺中IL-1β、IL-6、TNF-α和IL-8基因表达量在第1天显著升高(P<0.05),第5天显著降低(P<0.05);热应激模型鸡胸腺中IL-1β、IL-6、TNF-α和IL-8基因表达量显著升高(P<0.05);HSPA8基因在断喙后第1和3天胸腺中表达量显著升高(P<0.05),第5天显著降低(P<0.05);在持续热应激组中显著降低(P<0.05)。[结论]HSPA8基因参与鸡胸腺应激性免疫应答反应,可作为反映家禽是否处于应激性免疫抑制状态的可靠指标。以上结果为进一步研究HSPA8的免疫调控功能提供参考依据。
文摘Polyprenylated acylphloroglucinols represent an important class of natural products found in many plants.Among them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer properties.The two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol core.Their origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer activities.Both compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in vivo.They are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of action.The distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are discussed.The specific role of the chaperone protein HSPA8,known to interact with Ob-C,is addressed.Molecular models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition capacity.The review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.
基金H.L. and S.X.Z.were supported in part by NIH-NCI grants(R01CA095441,R01CA17246 and R01CA127724).
文摘The tumor suppressr p73 is a homolog of p53 and is capable of inducing cell cycle arrest and apoptosis.Here,we identify nerve growth factor receptor(NGFR,p75NTR,or CD271)as a novel negative p73 regulator.p73 activates NGFR transcription,which,in turn,promotes p73 degradation in a negative feedback loop.NGFR directly binds to p73 central DNA-binding domain and suppresses p73 transcriptional activity as well as p73-mediated apoptosis in cancer cells.Surprisingly,we uncover a previously unknown mechanism of NGFR-facilitated p73 degradation through the chaperone-mediated autophagy(CMA)pathway.Collectively,our studies demonstrate a new oncogenic function for NGFR in inactivating p73 activity by promoting its degradation through the CMA.
