excitation of glomus cells, namely membrane depolarization (accompanied by K+ current
suppression), influx of calcium through voltage gated channels, [Ca2+]c rise, neurotransmitter
release and neural discharge. Prolyl hydroxylase (PH) inhibition by Fe2+ chelation and by
inhibitors of 2-oxoglutarate was followed by same reactions and accumulation of HIF-1 _, and
led to carotid chemoreceptor excitation. Mitochondrial inhibitors inhibited HIF-1 _ accumulation
and thus would lead to loss of oxygen sensing. We conclude that HIF-1 _ accumulation equates to
chemosensing and chemosensory discharge.
127.
INTERMITTENT HYPOXIA INCREASES AT1 RECEPTOR AND OXIDATIVE STRESS IN
THE RAT CAROTID BODY. S.Y. Lam
1
, G.L. Tipoel
1
, Y.W. Tjiog
1
, E. Liong
1
, M.L. Fung
1
.
Departments of Physiology and Anatomy, University of Hong Kong, Pokfulam, Hong Kong,
China.
1
.
The carotid body (CB) plays an important role in cardiorespiratory changes in intermittent
hypoxia. Recent data suggest an involvement of angiotensin II (AT) and reactive oxygen species
in the pathophysiological development. The aim of this study was to examine the expression of
AT1 receptor and the by-products of oxidative stress in the CB of rats exposed to intermittent
hypoxia (IH, cyclic between air and 5% O2 per minute, 8 hour/day) or in isobaric chamber
breathing 10% O2 for chronic hypoxia (CH, 24 hour/day) for up to 4 weeks.
Immunohistochemical (IHC) studies revealed that, in the IH and CH groups, the
immunoreactivity (IR) of AT1 receptor was mainly observed in glomic clusters of the CB. The
AT1 receptor expression was markedly elevated in the 3-day IH group but not in the CH, and it
reached a plateau at day 7. Also, intracellular calcium response to AT was enhanced in the fura-2
loaded dissociated glomus cells from 3-day IH rats when compared with the normoxic controls.
Levels of oxidative stress in the CB were assessed by IHC method using specific antibody against
nitrotyrosine (NTR) and ELISA for the detection of total 8-isoprostane (IPT) in the serum. NTR-
IR and IPT levels were significantly elevated in 7-day IH group and returned to normoxic levels
by day 14, whereas mild expression of NTR and IPT were observed in the CH and normoxic
controls throughout the time course. These data suggest that oxidative stress occurred within the
first week in the IH but not with the CH group. In conclusion, the upregulation of the AT1
receptor expression may play a role in the enhancement of CB excitability during IH and this is
associated with oxidative stress during an early time course. (Supported by research grants from
Research Grants Council, HKSAR and the University of Hong Kong)
128.
PROLIFERATION INHIBITION AND APOPTOSIS ONSET IN HUMAN MAMMARY
CANCER CELL LINES MCF-7 INDUCED BY ZANGMUXIAN. Ma Lan
1
, Li Gao-Yuan
1
, Bai
Zhen-Zhong
1
, Yang Ying-Zhong
1
, Yun Hai-Xia
1
, Ge Ri-li
1
. Research Center for High Altitude
Medicine, Qinghai Medical College, Xining, R. P. China
1
.
It was reported that Tibetan medicineZangMuXiang_ZMX_Inula racemosa Hook.f.
possesses inhibitory effects on various tumor cells . But the report on the effects of ZMX on
human mammary cancer was rare and its antitumor mechanism was unclear. Aim: The present
study was performed to investigate the proliferation inhibition and apoptosis onset in human
mammary cancer cell lines MCF-7 induced by ZMX and to discuss its antitumor mechanism.
Methods: We adopted MTT method to test the inhibitory effect of ZMX on MCF-7 proliferation
in vitro. Apoptotic cell and apoptotic bodies were observed by acridine orange/ethidium bromide
(AO/EB) staining. The characteristic DNA ladders of apoptosis were determined by agarose gel
electrophoresis(AGE). Results: A time-dependent and dose-dependent proliferation inhibition of
ZMX was demonstrated in MCF-7, the prominent inhibitory concentrations were 100µg/ml and
50µg/ml and the 48h was the most apparent phase, the growth inhibition rates of the cancer cells
reached 47.62% and 41.19%, respectively. DNA ladder appeared by AGE. Conclusion: ZMX
could inhibit prolifetration and induce apoptosis in human mammary cancer cell lines MCF-7.
The work was funded by Natural Sceince Foundation of China (302600354)
