Kidney EPO Expression During Chronic Hypoxia in Aged Mice

Abstract

In order to maintain normal cellular function, mammalian tissue oxygen concentrations must be tightly regulated within a narrow physiological range. The hormone erythropoietin (EPO) is essential for maintenance of tissue oxygen supply by stimulating red blood cell production and promoting their survival. In this study we compared the effects of 290 Torr atmospheric pressure on the kidney EPO protein levels in young (4-month-old) and aged (24-month-old) C57BL/6 mice. The mice were sacrificed after being anesthetized, and kidney samples were collected and processed by Western blot analysis. Relatively low basal expression of EPO during normoxia in young mice showed significant upregulation in hypoxia and stayed upregulated throughout the hypoxic period (threefold compared to normoxic control), showing a slight decline toward the third week. Whereas, a relatively higher normoxic basal EPO protein level in aged mice did not show significant increase until seventh day of hypoxia, but showed significant upregulation in prolonged hypoxia. Hence, we confirmed that there is a progressively increased accumulation of EPO during chronic hypoxia in young and aged mouse kidney, and the EPO upregulation during hypoxia showed a similarity with the pattern of increase in hematocrit, which we have reported previously.

Sideroblastic anemia associated with multisystem mitochondrial disorders

“…48 Surprisingly, the specific cell type responsible for EPO production is still not firmly established, but several hypotheses have been proposed. 49,50 EPO is, to a lesser extent, also produced by the liver 51 and may cross the blood-brain barrier in several types of neuronal cells. 52 Our patient had profound cytochrome c oxidase deficiency in muscle and liver tissues.…”

Gender differences in hypoxic acclimatization in cyclooxygenase-2-deficient mice

“…). We have previously reported that kidney EPO was elevated throughout the 21‐day hypoxic period and peaked between 7 and 14 days (Benderro and LaManna ); hematocrit increased with continued hypoxia, doubling by 21 days (Benderro and LaManna , ). The relatively elevated basal kidney EPO and hematocrit level in the male KO mice may indicate a hypoxia‐like state in the kidney tissue and a diminishing of further hypoxic sensitivity, due to the deficiency of COX‐2.…”

“…). The 7‐day time point was chosen because we have previously reported that the peak elevation of EPO occurred at 7 days of hypoxia in kidney during chronic hypoxia in mice (Benderro and LaManna ). In the male mice, the normoxic baseline EPO in the KO group was significantly higher (50% increase) than the WT mice.…”

“…The hematologic acclimatization response, driven by kidney-produced erythropoietin, enables the maintenance of oxygen content in blood and improvement of tissue oxygenation despite decreased arterial partial pressure of O 2 (PaO 2 ) during hypoxia (Xu et al 2004). We have previously reported that kidney EPO was elevated throughout the 21-day hypoxic period and peaked between 7 and 14 days (Benderro and LaManna 2013); hematocrit increased with continued hypoxia, doubling by 21 days LaManna 2011, 2013). The relatively elevated basal kidney EPO and hematocrit level in the male KO mice may indicate a hypoxia-like state in the kidney tissue and a diminishing of further hypoxic sensitivity, due to the deficiency of COX-2.…”

Robustness during Aging—Molecular Biological and Physiological Aspects

“…If it were higher, the viscosity of the blood would be higher, so that it would flow more slowly. However, to maintain normal function, mammalian tissue oxygen concentrations must be tightly regulated within a narrow physiological range [ 126 ]. This explains, from a functional point of view, why it is beneficial to keep the Hct value constant during a lifetime.…”