Differentiation stage-specific requirement in hypoxia-inducible factor-1alpha-regulated glycolytic pathway during murine B cell development in bone marrow.
Differentiation stage-specific requirement in hypoxia-inducible factor-1alpha-regulated glycolytic pathway during murine B cell development in bone marrow.
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DOI：
10.4049/jimmunol.0800167
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Kobata T
中科院分区：
文献类型：
--
作者：
Kojima H;Kobayashi A;Sakurai D;Kanno Y;Hase H;Takahashi R;Totsuka Y;Semenza GL;Sitkovsky MV;Kobata T
缺氧诱导因子-1α（Hypoxia inducible factor-1 α，HIF-1α）在多种细胞氧平衡和糖酵解供能中起重要作用。我们以前报道过HIF-1α基因缺陷导致B细胞发育异常和自身免疫。在这里，我们表明，在B细胞发育过程中，HIF-1α激活的糖酵解是以发育阶段特异性的方式所必需的。支持这一结论的是观察到HIF-1α缺陷B220+骨髓细胞中的糖酵解途径在功能上比野生型对照细胞中的有效性低得多。在HIF-1α缺陷的细胞中，编码葡萄糖转运蛋白和关键糖酵解酶6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶3（pfkfb 3）的基因的表达显著降低。HIF-1α缺陷细胞对糖酵解缺陷的代偿性适应表现为糖酵解链相关基因和TCA循环相关基因的表达水平高于野生型细胞。与这些发现一致，HIF-1α缺陷细胞比野生型细胞更有效地利用丙酮酸。通过体外骨髓细胞培养过程中的葡萄糖剥夺和在骨髓细胞培养中使用糖酵解抑制剂，也证明了HIF-1α激活的糖酵解在骨髓B细胞中的关键作用。综上所述，这些发现表明，在B细胞发育的不同阶段，葡萄糖依赖性不同，HIF-1α在B细胞发育中起重要作用。
Hypoxia inducible factor –1α (HIF-1α) plays a central role in oxygen homeostasis and energy supply by glycolysis in many cell types. We previously reported that HIF-1α gene deficiency caused abnormal B cell development and autoimmunity. Here we show that HIF-1α-enabled glycolysis during B cell development is required in a developmental stage-specific manner. Supporting this conclusion are observations that the glycolytic pathway in HIF-1α deficient B220+ bone marrow cells is much less functionally effective than in wild-type control cells. The expression of genes encoding the glucose transporters and the key glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bishosphatase 3 (pfkfb3), was greatly reduced in HIF-1α deficient cells. The compensatory adaptation to the defect of glycolysis was reflected in higher levels of expression of respiratory-chain related genes and TCA-cycle related genes in HIF-1α deficient cells than in wild-type cells. In agreement with these findings, HIF-1α deficient cells utilized pyruvate more efficiently than wild-type cells. The key role of HIF-1α-enabled glycolysis in bone marrow B cells was also demonstrated by glucose deprivation during in vitro bone marrow cell culture and by using a glycolysis inhibitor in the bone marrow cell culture. Taken together, these findings indicate that glucose dependency differs at different B cell developmental stages and that HIF-1α plays important role in the B cell development.
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影响因子：
4.8
作者：
Minchenko, A;Leshchinsky, I;Caro, J
通讯作者：
Caro, J
影响因子：
4.4
作者：
Huang, Julie H.;Cardenas-Navia, L. Isabel;Dustin, Michael L.
通讯作者：
Dustin, Michael L.
DOI：
10.1073/pnas.91.14.6496
发表时间：
1994-07-05
影响因子：
11.1
作者：
FIRTH, JD;EBERT, BL;RATCLIFFE, PJ
通讯作者：
RATCLIFFE, PJ
影响因子：
--
作者：
Hamilton, JA;Callaghan, MJ;Watts, CKW
通讯作者：
Watts, CKW
DOI：
10.1159/000015181
发表时间：
1998-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Manzano, A;Rosa, JL;Bartrons, R
通讯作者：
Bartrons, R