Role of TASK2 in the Control of Apoptotic Volume Decrease in Proximal Kidney Cells

The purpose of this study was to examine the inability of paraplegic (P) subjects to redistribute fluid below the spinal cord lesion during arm exercise, with emphasis on the role of the sympathetic system in this redistribution failure. Fifteen male P and 15 male able-bodied [control (C)] subjects performed arm cranking exercise, and volume changes in the calf were measured by strain gauge plethysmography before, during, and after exercise. Muscle pump activity in the legs of C subjects was eliminated. The rate of calf volume decrease at the beginning and halfway points of the exercise period, the total volume decrease during exercise, and the volume increase during recovery were significantly lower in P than in C subjects. Whereas completeness of the lesion had no influence on leg volume changes, the rate of calf volume decrease at the beginning of exercise and the total volume decrease during exercise were significantly correlated with the level of the spinal cord lesion. This study confirms that P subjects are unable to redistribute fluid effectively below the spinal cord injury during arm exercise, which is partly caused by a loss of sympathetically induced vasoconstriction and which appears to be independent of the completeness of the lesion but dependent on its level.

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Heme oxygenase-2 (HO-2) binds and buffers labile heme, which is largely oxidized, in human embryonic kidney cells

10.1101/2021.06.06.447256 ◽

2021 ◽

Author(s):

David A Hanna ◽

Courtney M Moore ◽

Liu Liu ◽

Xiaojing Yuan ◽

Angela S Fleischhacker ◽

...

Keyword(s):

Oxidative Stress ◽

Physiological Function ◽

Hek293 Cells ◽

Kidney Cells ◽

Human Embryonic Kidney ◽

Human Embryonic Kidney Cells ◽

Heme Oxygenases ◽

Heme Trafficking ◽

Ferrous Heme

Heme oxygenases (HO) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin and excreted. Humans express two isoforms: inducible HO-1, which is up-regulated in response to various stressors, including excess heme, and constitutive HO-2. While much is known about the regulation and physiological function of HO-1, comparatively little is known about the role of HO-2 in regulating heme homeostasis. The biochemical necessity for expressing constitutive HO-2 is largely dependent on whether heme is sufficiently abundant and accessible as a substrate under conditions in which HO-1 is not induced. By measuring labile heme, total heme, and bilirubin in human embryonic kidney HEK293 cells with silenced or over-expressed HO-2, and various HO-2 mutant alleles, we found that endogenous heme is too limiting to support HO-2 catalyzed heme degradation. Rather, we discovered that a novel role for HO-2 is to bind and buffer labile heme. Taken together, in the absence of excess heme, we propose that HO-2 regulates heme homeostasis by acting as a heme buffering factor in control of heme bioavailability. When heme is in excess, HO-1 is induced and both HO-2 and HO-1 can provide protection from heme toxicity by enzymatically degrading it. Our results explain why catalytically inactive mutants of HO-2 are cytoprotective against oxidative stress. Moreover, the change in bioavailable heme due to HO-2 overexpression, which selectively binds ferric over ferrous heme, is consistent with the labile heme pool being oxidized, thereby providing new insights into heme trafficking and signaling.

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