Action mechanisms of a new erythrocyte-derived depressing factor

Autor: Fang Wan, Yunyi Wen, Xiaochun Zhang, Xiaorong Xu, Guiqing Zhao
Rok vydání: 2000
Předmět:
Zdroj: Chinese Science Bulletin. 45:2113-2118
ISSN: 1861-9541
1001-6538
Popis: To investigate the action mechanisms of a new erythrocyte-derived depressing factor (EDDF), the focus is placed on the effect of EDDF on both cytosolic and nuclear free calcium (Ca2+) transportation in vascular smooth muscle cell (VSMC), as well as the apoptosis and cell cycle of VSMC of rats. EDDF has been extracted from human erythrocytes. The changes of Ca2+ levels in cytoplasm ([Ca2+]i) and nucleus ([Ca2+]n) have been observed using a laser scanning confocal microscope together with fluo-3/AM as a calcium indicator. Flow cytometric technique was used to study the effect of EDDF on cell cycle and apoptosis of VSMC. [Ca2+], and [Ca2+]n were significantly decreased through several different pathways: ( i ) it reduced the Ca2+ influx by blocking L-type voltage-dependent calcium channel (L-VDC) and R-type voltage-dependent calcium channel (R-VDC); (ii) it inhibited the Ca2+ release from inositol 1, 4, 5-trisphosphate (IP3) sensitive calcium store; and (iii) activated Ca2+-ATPase of sarcoplasmic reticulum (SR) and promoted the transportation of Ca2+ from cytoplasm to SR. However, EDDF seemed to have little inhibitory effect on the Ca2+ release from ryonodine sensitive calcium pool. It was also found that EDDF (10−4 g/mL) significantly decreased the proportion of S phase of human umbilical vein (HUV) and inhibited the proliferation of VSMC induced by angiotensin II (Angll, 10−5 mol/L). The apopotosis did not occur when VSMC was cultured under normal condition. While VSMC apoptosis was induced by Angll (10−5 mol/L) and EDDF (10−4 g/mL) seemed to have little effect on it. The inhibitory effect of EDDF on the elevation of [Ca2+]i and [Ca2+]n of VSMC might play an essential role in its action mechanisms and the ways it affects the Ca2+ handling of VSMC demonstrate that EDDF was different from other endogenous blood pressure regulators and some known antihypertensive drugs. EDDF could inhibit the proliferation of VSMC, which indicated that it might be beneficial to the prevention and treatment of hypertension and arteriosclerosis.
Databáze: OpenAIRE
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