Cross-Linking of Cell Surface Receptors as a Trigger of Cell Apoptosis and Proliferation

A hypothesis of the mechanism by which the protein cross-linking agents trigger apoptosis of lymphoid cells and proliferation of other cell types is proposed. It is assumed that both effects are triggered by aggregation of receptors on cell surface, which results from their cross-linking. This idea is substantiated by the example of one of these agents, ionizing radiation. As in the case of physiological agents, such as, antigens and growth factors, the aggregation of receptors induced by radiation activates receptor protein tyrosine kinases from which the signal is transduced to genes through protein kinase C. The hypothesis is consistent with the relationship between these effects and the PTK-PKC-dependent signal transduction pathway and its activation after irradiation

Thymocyte Proliferation and Apoptosis Induced by Ionizing Radiation

Proliferation and apoptosis of rat and mouse thymocytes caused by ionizing radiation were studied. The percentage of proliferating cells was determined by the method of colchicine metaphases and the apoptosis was estimated as DNA fragmentation. In vitro irradiation with 0.05-0.2 Gy was found to stimulate thymocyte proliferation, the maximum was observed at 0.05 Gy for mouse thymocytes and at 0.1 Gy for rat thymocytes. These doses caused a slight decrease in DNA fragmentation, as compared to control. By raising the radiation dose, proliferation was reduced and DNA fragmentation was increased. The results obtained indicate that low radiation doses stimulate cell proliferation while higher doses trigger apoptosis of thymocytes

On the role of intracellular concentration of Ca2+ and H+ in thymocyte death after irradiation

AbstractThe role of intracellular Ca2+ and H+ concentrations in radiation-induced interphase death of rat thymocytes has been studied. In response to concanavalin A treatment in the Ca2+-containing medium, or to the CaCl2 treatment in the Ca2+-free medium, the [Ca2+]i rise in irradiated cells was as in the non-treated cells. No changes in the level of [Ca2+]i and pHi were found within l h after irradiation of thymocytes with a dose of 6 Gy. 15 μM 5-(N-ethyl-N-isopropyl)-amiloride. an inhibitor of Na+/H+ exchange, did not affect the DNA fragmentation. The fragmentation was prevented by 2–4 μM (1 -[bis(4-chlorophenyl)methyl]-3-[2-(2,4-dichlorophenyl)]-2-[(2,4-dichlorophenyl)-methoxy]-ethyl)-1 -H-imidazoliumchloride, an inhibitor of calmodulin. The above data indicate that triggering of interphase death in irradiated thymocytes is not mediated by changes in either [Ca2+]i or pHi. Such changes seem to be involved in intermediate steps of the interphase death process

Low doses of ethanol decrease the activity of the angiotensin-converting enzyme in the aorta of aging rats and rats treated with a nitric oxide synthase inhibitor and dexamethasone

A B S T R A C T In the present study, the activity of ACE (angiotensin-converting enzyme) in the aorta of senescent rats and rats treated with the NOS (NO synthase) inhibitor L-NAME (N G -nitro-L-arginine methyl ester) or dexamethasone and the effect of low doses of ethanol (0.2-1.2 g/kg of body weight, daily for 8-12 days) on this activity were studied. We found that ACE activity increased with age and in response to L-NAME and dexamethasone treatment. Ethanol at a dose of 0.4 g/kg of body weight per day decreased ACE activity in the aorta of aged rats and of rats treated with L-NAME or dexamethasone to the level of activity in young control rats. The optimal ethanol dose (the dose inducing a maximum decrease in ACE activity) increased with increasing doses of dexamethasone: 0.4 g/kg of body weight per day at 30 μg of dexamethasone/kg of body weight and 0.8 g/kg of body weight per day at 100 μg of dexamethasone/kg of body weight. It was also found that optimal doses of ethanol increased the number of cells in the thymus of rats treated with dexamethasone. The optimal dose of ethanol of 0.4 g/kg of body weight per day, which induced a maximum decrease in ACE activity in rat aorta, corresponded to a dose of 30 g of ethanol/day, which, according to epidemiological data, produces a maximum decrease in the incidence of cardiovascular disease in humans. In conclusion, the decrease in ACE activity in vessels may be one of the main mechanisms of the beneficial effects of low doses of ethanol on human health

(+)-Catechin Stereoisomer and Gallate Induce Oxidative Stress in Rat Aorta

The goal of the work was to study changes in the activity of the angiotensin-converting enzyme (ACE) and production of reactive oxygen species (ROS) in the aorta of rats after the intraperitoneal injection of stereoisomers of catechin and gallate. The activity of ACE in the aorta sections was determined by measuring the hydrolysis of hippuryl-l-histidyl-l-leucine. The production of ROS in the aorta sections was estimated from the oxidation of dichlorodihydrofluorescein. The time and dose dependences of the effect of catechin stereoisomers and gallate on ACE activity and ROS production in the aorta were studied. It was shown that (+)-catechin and gallate increased the ACE activity and ROS production, and (−)-catechin and (−)-epicatechin did not influence these parameters. The doses of (+)-catechin and gallate that increased the ACE activity to a half-maximal value (AD50) were 0.04 and 0.03 µg/kg, respectively. Fucoidin, a blocker of leukocyte adhesion to the endothelium, reduced the ACE activity to the control level in the aortas of (+)-catechin-treated rats