Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin
Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin
复制标题
DOI：
10.1172/jci13292
复制
发表时间：
2002-01-01
影响因子：
15.9
通讯作者：
Al-Awqati, Q
中科院分区：
文献类型：
--
作者：
Schwartz, GJ;Tsuruoka, S;Al-Awqati, Q
代谢性酸中毒引起皮质集管（CCD）中HCO3-通量极性逆转。在体外酸性培养基中培养的ccd中，β插层（分泌HCO3）细胞被重塑为在功能上类似于cc插层（分泌H+）细胞。在细胞培养过程中，嵌入β的细胞也发生了类似的重塑，其中H+泵和Cl-/HCO3-交换器的极性被逆转，这需要在ECM中沉积聚合的母鸡素。在体外低pH下维持3小时的ccd显示出HCO3-通量的逆转，这在数量上类似于先前在体内酸处理的兔子中观察到的效果。我们在酸培养前后观察了相同的β -插层细胞的细胞内pH值，发现酸培养后顶端Cl/HCO3交换被消除。一些细胞还发生基底侧Cl-/HCO3-交换，表明插入细胞极性逆转。这种适应需要完整的微管和微丝，以及新的蛋白质合成，并且与β -嵌入细胞的顶端表面变小有关。抗母鸡素抗体的加入阻止了酸诱导的相同细胞顶侧和基底侧Cl-/HCO3-交换的变化以及相应的HCO3-分泌的抑制。酸负载也促进了在适应β嵌入细胞下的ECM中母鸡素的沉积。因此，酸培养过程中β -嵌入细胞向α -嵌入细胞的适应性转化依赖于ecm相关的母鸡素。
Metabolic acidosis causes a reversal of polarity of HCO3- flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, beta-intercalated (HCO3--secreting) cells are remodeled to functionally resemble cc-intercalated (H+-secreting) cells. A similar remodeling of beta-intercalated cells, in which the polarity of H+ pumps and Cl-/HCO3- exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO3- flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same beta-intercalated cells before and after acid incubation and found that apical Cl/HCO3 exchange was abolished following acid incubation. Some cells also developed basolateral Cl-/HCO3- exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of beta-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl-/HCO3- exchange observed in the same cells and the corresponding suppression of HCO3- secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting beta-intercalated cells. Hence, the adaptive conversion of beta-intercalated cells to alpha-intercalated cells during acid incubation depends upon ECM-associated hensin.