title: ÐÐ½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½ÑÐµ Ð¿ÑÐ¾ÑÐµÐ°Ð·Ñ ÐºÐ°Ðº ÑÐµÐ³ÑÐ»ÑÑÐ¾ÑÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð°ÐºÑÐ¸Ð½-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÑ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² Ð² ÐºÐ»ÐµÑÐºÐ°Ñ Ð»ÐµÐ¹ÐºÐµÐ¼Ð¸Ð¸ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ° Ð562
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Extracellular proteases as regulators of the activity of actin-gated sodium channels in K562 human leukemia cells
Creators: name: ÐÑÑÐ¸ÐºÐ¾Ð²Ð°, ÐÐ°ÑÑÑ
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2022
Subjects: ÐÐ¸Ð¾ÑÐµÑ Ð½Ð¾Ð»Ð¾Ð³Ð¸Ñ
ÐÐ»ÐµÑÐºÐ° (Ð±Ð¸Ð¾Ð».)
Ð°ÐºÑÐ¸Ð½-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÐµ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÐµ ÐºÐ°Ð½Ð°Ð»Ñ
ÑÐ¿Ð¸ÑÐµÐ»Ð¸Ð°Ð»ÑÐ½ÑÐµ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÐµ ÐºÐ°Ð½Ð°Ð»Ñ
ÐºÐ»ÐµÑÐºÐ¸ Ð»ÐµÐ¹ÐºÐµÐ¼Ð¸Ð¸
ÑÐµÑÐ¸Ð½Ð¾Ð²ÑÐµ Ð¿ÑÐ¾ÑÐµÐ°Ð·Ñ
Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½
Ð¿ÑÐ¾ÑÐµÐ¾Ð»Ð¸ÑÐ¸ÑÐµÑÐºÐ°Ñ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ñ
Ð»ÐµÐ¹ÐºÐ¾Ð·Ð½ÑÐµ ÐºÐ»ÐµÑÐºÐ¸ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ°
epithelial sodium channels
actin-gated channels
serine proteases
extracellular proteases
plasmin
protease cleavage
human leukemia cells

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸Ð·ÑÑÐµÐ½Ð¸Ñ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÐµÑÐ¸Ð½Ð¾Ð²ÑÑ Ð¿ÑÐ¾ÑÐµÐ°Ð· ÑÐ°Ð·Ð»Ð¸ÑÐ½Ð¾Ð¹ ÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐ½Ð¾ÑÑÐ¸ Ð½Ð° Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð°Ð¼Ð¸Ð»Ð¾ÑÐ¸Ð´-Ð½ÐµÑÑÐ²ÑÑÐ²Ð¸ÑÐµÐ»ÑÐ½ÑÑ Ð°ÐºÑÐ¸Ð½-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² ENaC Ð² ÐºÐ»ÐµÑÐºÐ°Ñ Ð»ÐµÐ¹ÐºÐµÐ¼Ð¸Ð¸ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ° Ð562. Ð ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ°Ñ whole-cell Ð±ÑÐ»Ð° Ð¾Ð±Ð½Ð°ÑÑÐ¶ÐµÐ½Ð° Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ñ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² ENaC Ð² ÐºÐ»ÐµÑÐºÐ°Ñ Ð562 Ð¿ÑÐ¸ Ð²Ð½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð¼ Ð¿ÑÐ¸Ð»Ð¾Ð¶ÐµÐ½Ð¸Ð¸ ÑÑÐ¸Ð¿ÑÐ¸Ð½Ð°, âÑÐ¸Ð¼Ð¾ÑÑÐ¸Ð¿ÑÐ¸Ð½Ð° Ð¸Ð»Ð¸ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½Ð°. ÐÑÐ»Ð¾ ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¾, ÑÑÐ¾ Ð·Ð°ÑÐµÐ³Ð¸ÑÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÐµ ÐºÐ°Ð½Ð°Ð»Ñ Ð½Ðµ ÑÑÐ²ÑÑÐ²Ð¸ÑÐµÐ»ÑÐ½Ñ Ðº Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´Ð½Ð¾Ð¼Ñ Ð°Ð¼Ð¸Ð»Ð¾ÑÐ¸Ð´Ð° Ð±ÐµÐ½Ð·Ð°Ð¼Ð¸Ð»Ñ, Ð° Ð¸Ñ ÑÑÐ½ÐºÑÐ¸Ð¾Ð½Ð°Ð»ÑÐ½ÑÐµ ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸ÑÑÐ¸ÐºÐ¸ (Ð¿ÑÐ¾Ð²Ð¾Ð´Ð¸Ð¼Ð¾ÑÑÑ, Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð» ÑÐµÐ²ÐµÑÑÐ¸Ð¸) Ð¸Ð´ÐµÐ½ÑÐ¸ÑÐ½Ñ ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸ÑÑÐ¸ÐºÐ°Ð¼ ÐºÐ°Ð½Ð°Ð»Ð°Ð¼, Ð°ÐºÑÐ¸Ð²Ð¸ÑÑÐµÐ¼ÑÐ¼ Ð¿ÑÐ¸ ÑÐ°Ð·Ð±Ð¾ÑÐºÐµ Ð°ÐºÑÐ¸Ð½Ð¾Ð²Ð¾Ð³Ð¾ ÑÐ¸ÑÐ¾ÑÐºÐµÐ»ÐµÑÐ° ÑÐ¸ÑÐ¾ÑÐ°Ð»Ð°Ð·Ð¸Ð½Ð¾Ð¼ Ð. Ð£ÑÐ°ÑÑÐ¸Ðµ Ð¿ÑÐ¾ÑÐµÐ¾Ð»Ð¸ÑÐ¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÐµÑÐ¸Ð½Ð¾Ð²ÑÑ Ð¿ÑÐ¾ÑÐµÐ°Ð· (-ÑÐ¸Ð¼Ð¾ÑÑÐ¸Ð¿ÑÐ¸Ð½Ð° Ð¸Ð»Ð¸ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½Ð°) Ð±ÑÐ»Ð¾ Ð¿Ð¾Ð´ÑÐ²ÐµÑÐ¶Ð´ÐµÐ½Ð¾ Ð² Ð¾Ð¿ÑÑÐ°Ñ whole-cell Ñ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð¸ÐµÐ¼ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ¾Ð² (SBTI Ð¸Ð»Ð¸ Î±2-Ð°Ð½ÑÐ¸Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½Ð° ÑÐ¾Ð¾ÑÐ²ÐµÑÑÑÐ²ÐµÐ½Ð½Ð¾). ÐÐ¾Ð±Ð°Ð²Ð»ÐµÐ½Ð¸Ðµ Ð²Ð¾ Ð²Ð½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½ÑÐ¹ ÑÐ°ÑÑÐ²Ð¾Ñ -ÑÐ¸Ð¼Ð¾ÑÑÐ¸Ð¿ÑÐ¸Ð½Ð° Ð¸Ð»Ð¸ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½Ð°, Ð¿ÑÐµÐ´Ð²Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾ Ð¿ÑÐ¾Ð¸Ð½ÐºÑÐ±Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ Ñ Ð¸Ñ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ°Ð¼Ð¸, Ð½Ðµ Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ð»Ð¾ Ðº Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¸Ð¸ ÐºÐ°Ð½Ð°Ð»Ð¾Ð². Ð ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÐ°Ñ cell-attached Ð¿Ð¾Ð´ÑÐ²ÐµÑÐ¶Ð´ÐµÐ½Ð¾, ÑÑÐ¾ Ð¿ÑÐ¾ÑÐµÐ°Ð·Ñ Ð½Ð°Ð¿ÑÑÐ¼ÑÑ, Ð° Ð½Ðµ Ð¾Ð¿Ð¾ÑÑÐµÐ´Ð¾Ð²Ð°Ð½Ð½Ð¾, Ð´ÐµÐ¹ÑÑÐ²ÑÑÑ Ð½Ð° Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð². Ð ÐµÐ·ÑÐ»ÑÑÐ°ÑÑ Ð¸Ð¼Ð¼ÑÐ½Ð¾ÑÐ»ÑÐ¾ÑÐµÑÑÐµÐ½ÑÐ½Ð¾Ð³Ð¾ Ð¾ÐºÑÐ°ÑÐ¸Ð²Ð°Ð½Ð¸Ñ Ð¿Ð¾Ð´ÑÐ²ÐµÑÐ¶Ð´Ð°ÑÑ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ðµ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½Ð° Ð½Ð° -ENaC. ÐÐ±Ð½Ð°ÑÑÐ¶ÐµÐ½Ð¾, ÑÑÐ¾ âÑÐ¸Ð¼Ð¾ÑÑÐ¸Ð¿ÑÐ¸Ð½ Ð¸ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½ ÑÐ¼ÐµÐ½ÑÑÐ°ÑÑ Ð¼Ð¸Ð³ÑÐ°ÑÐ¸Ñ Ð¸ Ð½Ðµ Ð¾ÐºÐ°Ð·ÑÐ²Ð°ÑÑ ÑÑÑÐµÐºÑÐ° Ð½Ð° Ð¸Ð½Ð²Ð°Ð·Ð¸Ñ ÐºÐ»ÐµÑÐ¾Ðº Ð»ÐµÐ¹ÐºÐµÐ¼Ð¸Ð¸ Ð562, Ð² ÑÐ¾ Ð²ÑÐµÐ¼Ñ ÐºÐ°Ðº SBTI ÑÐ¾ÑÐ¼Ð¾Ð·Ð¸Ñ Ð¸Ð½Ð²Ð°Ð·Ð¸Ñ ÐºÐ»ÐµÑÐ¾Ðº, Ð° Î±2âÐ°Ð½ÑÐ¸Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½ â Ð½Ð°Ð¾Ð±Ð¾ÑÐ¾Ñ Ð¿ÑÐ¸Ð²Ð¾Ð´Ð¸Ñ Ðº ÐµÐµ ÑÑÐºÐ¾ÑÐµÐ½Ð¸Ñ. ÐÑÐ¾Ð´ÐµÐ¼Ð¾Ð½ÑÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð¾,Â ÑÑÐ¾ Ð¿Ð»Ð°Ð·Ð¼Ð¸Ð½ ÑÑÐºÐ¾ÑÑÐµÑ Ð¿ÑÐ¾Ð»Ð¸ÑÐµÑÐ°ÑÐ¸Ñ ÐºÐ»ÐµÑÐ¾Ðº Ð562. Ð¢Ð°ÐºÐ¸Ð¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼, Ð¼Ð¾Ð¶Ð½Ð¾ ÑÐ´ÐµÐ»Ð°ÑÑ Ð²ÑÐ²Ð¾Ð´, ÑÑÐ¾ ÑÐµÑÐ¸Ð½Ð¾Ð²ÑÐµ Ð¿ÑÐ¾ÑÐµÐ°Ð·Ñ Ð¼Ð¾Ð³ÑÑ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°ÑÑÑÑ ÐºÐ°Ðº ÑÐ½Ð¸Ð²ÐµÑÑÐ°Ð»ÑÐ½ÑÐµ Ð²Ð½ÐµÐºÐ»ÐµÑÐ¾ÑÐ½ÑÐµ ÑÐµÐ³ÑÐ»ÑÑÐ¾ÑÑ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð°ÐºÑÐ¸Ð½-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÑ Ð½Ð°ÑÑÐ¸ÐµÐ²ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² Ð² ÐºÐ»ÐµÑÐºÐ°Ñ Ð562. ÐÐ°Ð»ÑÐ½ÐµÐ¹ÑÐµÐµ Ð¸Ð·ÑÑÐµÐ½Ð¸Ðµ Ð¿ÑÐ¾ÑÐµÐ¾Ð»Ð¸ÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ ENaC Ð² ÑÑÐ°Ð½ÑÑÐ¾ÑÐ¼Ð¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ ÐºÐ»ÐµÑÐºÐ°Ñ ÐºÑÐ¾Ð²Ð¸ Ð¿Ð¾Ð·Ð²Ð¾Ð»Ð¸Ñ Ð¿ÑÐµÐ´Ð¿Ð¾Ð»Ð¾Ð¶Ð¸ÑÑ Ð½Ð¾Ð²ÑÐµ ÑÐ¿Ð¾ÑÐ¾Ð±Ñ ÐºÐ¾Ð½ÑÑÐ¾Ð»Ñ Ð¼Ð¸Ð³ÑÐ°ÑÐ¸Ð¸ Ð¸ ÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð³Ð¾ ÑÐ¾ÑÑÐ° ÑÐ°ÐºÐ¾Ð²ÑÑ ÐºÐ»ÐµÑÐ¾Ðº.
description: The given work is devoted to the investigation of the effects of serine proteases with different specificity on the activity of amiloride-insensitive actinâgated ENaC channels in human leukemia cells.In whole-cell experiments, extracellular application of trypsin, âchymotrypsin, or plasmin caused an activation of ENaC sodium channels in human leukemia cells. It was found that the activated channels were not sensitive to the amiloride derivative benzamyl, and its functional characteristics (conductivity, reversion potential) were identical to the characteristics of actin-gated channels activated during disassembly of the actin cytoskeleton by cytochalasin D. The proteolytic action of serine proteases (-chymotrypsin or plasmin) was confirmed in whole-cell experiments by using inhibitors (SBTI or Î±2âantiplasmin, respectively). The addition to the extracellular solution of âchymotrypsin or plasmin previously preincubated with their inhibitors did not cause channel activation. Cell-attached experiments confirmed that proteases act directly, rather than indirectly mediated, on the sodium channels activity. The results of immunofluorescent staining confirmed the effect of plasmin on -ENaC. It was found that -chymotrypsin and plasmin decrease migration rate and have no effect on invasion of human leukemia cells, while SBTI inhibits cell invasion, Î±2-antiplasmin, in contrast, promotes cells invasion. It was demonstrated that plasmin slightly increased the proliferation rate of human leukemia cells. Thus, we can conclude that serine proteases can be used as universal extracellular regulators ofÂ the activity of actin-gated sodium channels in human leukemia cells. Further study of the proteolytic regulation of ENaC in transformed blood cells could be useful for development of new ways to control migration and cell growth of cancer cells.