The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

Abraham, Soman N.; Lin, Chu Yuan; Klein, Harold P.; Volkmann, Carol M.

doi:10.1016/0273-1177(81)90263-5

Cited by 16 publications

(11 citation statements)

References 16 publications

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“…These indicate that analysis of individual CYP expression is necessary to understand metabolic status during spaceflight. The glycogen content of the liver in FL rats is significantly elevated irrespective of flight duration but the change in lipid composition is inconsistent among reports 1,20 . Hepatic lipid accumulation in rats is reported to upregulate CYP4A1 21 .…”

Section: Discussionmentioning

confidence: 98%

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Baba

Nishimura

Kuwahara

et al. 2008

Pathology International

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As the incidence and length of spaceflight increases, the need to administer pharmacological agents to crew members may become greater. The final goal is to predict the therapeutic or toxic effects of drugs, especially those with a low therapeutic index, during spaceflight. The liver is central to systemic metabolism, therefore, various drugs rely on hepatic metabolism by cytochrome P450 (CYP). The function of individual CYP enzymes is diverse because they are subject to different regulatory mechanisms and substrate specificity. Because spaceflight may be a stressor and influence each CYP expression individually, the purpose of the present study was to measure the expression of 11 CYP genes and protein distribution in the liver of rats after spaceflight, using real-time polymerase chain reaction and immunohistochemistry, respectively. The gene and protein expression of stress-related proteins such as cold-inducible RNA binding protein (Cirp), heat shock protein 70 (HSP70), HSP90 and the p53 tumor suppressor gene, were also determined. CYP4A1and Cirp gene expression was significantly increased whereas HSP90 and p53 gene expression was significantly decreased in the flight group than in the ground control. Combined with histology, it is concluded that the effects of spaceflight on the liver may be similar to mild cold stress or fasting.

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Section: Discussionmentioning

confidence: 98%

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Baba

Nishimura

Kuwahara

et al. 2008

Pathology International

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“…3, 4, 5, 6, 50, 51 Previous reports have shown that microgravity induces hepatic injury and apoptosis. 8, 9 It is well known that hepatocyte proliferation is associated with various types of injuries; however, less is known regarding the connection between liver function injury and hepatocyte cell cycle control under microgravity.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-223 in the rat liver inhibits proliferation of hepatocytes under simulated microgravity

Chen

Yang

et al. 2017

Exp Mol Med

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Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports. Next, we demonstrated that the cell proliferation activity, determined by Ki67, PCNA and PH3, was significantly decreased at the different TS time points (TS for 14, 28 and 42 days) compared with that in the control group. Consistently, the positive cell cycle regulators Ccna2, Ccnd1, Cdk1, Cdk2 and cyclin D3 were also significantly decreased in the TS groups as shown by quantitative real-time PCR and western blotting analysis. Subsequent analysis revealed that the aberrant hepatocyte proliferation inhibition under simulated microgravity was associated with the upregulation of miR-223 in the liver. We further found that miR-223 inhibited the proliferation of Hepa1-6 cells and identified CDK2 and CUL1 as its direct targets. In addition, the decreased expression of CDK2 and CUL1 was negatively correlated with the level of p27 in vitro and in vivo, which may have been responsible for retarding hepatocyte proliferation. Collectively, these data indicate that upregulation of miR-223 was associated with the inhibition of liver cell growth and reveal the role of miR-223 in rat hepatocyte proliferation disorders and the pathophysiological process under simulated microgravity.

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“…Rats flown for 18.5 days in a biosatellite showed decreased liver enzyme activity of glycogen phosphorylase, which is involved in glycogenolysis. [24][25][26] Mice flown for 30 days were subjected to liver examination by proteomics analysis 1 week following return to Earth. Proteins related to amino acid metabolism marked higher levels after re-adaption, which may suggest increased rates of gluconeogenesis.…”

Section: Effec Ts Of S Pacefli G Ht and S Imul Ated MI Crog R Avit Y ...mentioning

confidence: 99%

“…Increased glucose plasma levels 8,22 as well as changes in insulin receptors in liver 23 are also observed in rats following spaceflight (Table 2). Rats flown for 18.5 days in a biosatellite showed decreased liver enzyme activity of glycogen phosphorylase, which is involved in glycogenolysis 24–26 . Mice flown for 30 days were subjected to liver examination by proteomics analysis 1 week following return to Earth.…”

Section: Effects Of Spaceflight and Simulated Microgravity On Carbohy...mentioning

confidence: 99%

Hepatology in space: Effects of spaceflight and simulated microgravity on the liver

Vinken

2022

Liver International

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Microgravity as experienced during spaceflight affects a number of physiological processes in various organs. However, effects on the liver have yet been poorly documented. Nevertheless, the liver is a metabolically highly active organ involved in carbohydrate metabolism, lipid metabolism and xenobiotic biotransformation. The present paper provides an overview of the effects of microgravity on the liver observed in experimental animals during actual spaceflight and upon simulation of microgravity on Earth. These include (i) induction of liver injury and inflammation associated with apoptosis and oxidative stress, (ii) changes in liver carbohydrate metabolism resulting in the onset of a diabetogenic phenotype, (iii) modifications in hepatic lipid metabolism leading to early non‐alcoholic fatty liver disease and (iv) alterations of the hepatic xenobiotic biotransformation machinery. Although most of these observations remain to be fully validated in humans, appropriate measures to counteract liver pathogenesis should be considered, especially in view of long‐term space missions.

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The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

Cited by 16 publications

References 16 publications

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Upregulation of miR-223 in the rat liver inhibits proliferation of hepatocytes under simulated microgravity

Hepatology in space: Effects of spaceflight and simulated microgravity on the liver

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