Heme Oxygenase 1 and 2 Differentially Regulate Glucose Metabolism and Adipose Tissue Mitochondrial Respiration: Implications for Metabolic Dysregulation

Yao, Hongwei; Peterson, Adam; Li, Jie; Xu, Haiyan; Dennery, Phyllis A.

doi:10.3390/ijms21197123

Cited by 16 publications

(13 citation statements)

References 62 publications

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“…The results showed that the GA content increased by 60.1% and 56.0% and decreased by 26.0%, while the enzymatic activity of HO increased by 57.1% and 18.1% and decreased by 15.8%, respectively [ 42 ]. In addition to fungi, HO was vital for modulating glucose and energy metabolism in mammals [ 43 ]. In this study, we speculated that HO could participate in the regulation of GA content through its catalytic product CO.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase/Carbon Monoxide Participates in the Regulation of Ganoderma lucidum Heat-Stress Response, Ganoderic Acid Biosynthesis, and Cell-Wall Integrity

Liu

Wang

et al. 2022

IJMS

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Carbon monoxide (CO), a product of organic oxidation processes, arises in vivo principally from the enzymatic reaction of heme oxygenase (HO, transcription gene named HMX1). HO/CO has been found to exert many salutary effects in multiple biological processes, including the stress response. However, whether HO/CO is involved in the regulation of the heat-stress (HS) response of Ganoderma lucidum (G. lucidum) is still poorly understood. In this paper, we reported that under heat stress, the HMX1 transcription level, HO enzyme activity, and CO content increased by 5.2-fold, 6.5-fold and 2-fold, respectively. HMX1 silenced strains showed a 12% increase in ganoderic acid (GA) content under HS as analyzed by HPLC. Furthermore, according to Western blot analysis of the protein phosphorylation levels, HMX1 attenuated the increase in phosphorylation levels of slt2, but the phosphorylation levels were prolonged over a 3 h HS time period. The chitin and glucan content in HMX1 silenced strains increased by 108% and 75%, respectively. In summary, these findings showed that the HO/CO system responds to heat stress and then regulates the HS-induced GA biosynthesis and the cell-wall integrity mediated by the Slt-MAPK phosphorylation level in G. lucidum.

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Section: Discussionmentioning

confidence: 99%

Heme Oxygenase/Carbon Monoxide Participates in the Regulation of Ganoderma lucidum Heat-Stress Response, Ganoderic Acid Biosynthesis, and Cell-Wall Integrity

Liu

Wang

et al. 2022

IJMS

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“…Nrf2 has also been shown to reduce lipid accumulation and oxidative damage in mice with hepatic steatosis ( Upadhyay et al, 2020 ). Recent studies in humans have linked HMOX2, Nrf2, and IL-1β with insulin resistance and obesity ( Li et al, 2012 , 2020 ; Crilly et al, 2016 ; Tan et al, 2018 ; Yao et al, 2020 ), which are two characteristics exhibited by fasting NES ( Houser et al, 2013 ). Evidently, more research is needed to understand the link between CO and IL1B expression in diving, fasting-adapted mammals.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of Carbon Monoxide-Related Gene Expression in a Deep-Diving Marine Mammal

et al. 2021

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Marine mammals such as northern elephant seals (NES) routinely experience hypoxemia and ischemia-reperfusion events to many tissues during deep dives with no apparent adverse effects. Adaptations to diving include increased antioxidants and elevated oxygen storage capacity associated with high hemoprotein content in blood and muscle. The natural turnover of heme by heme oxygenase enzymes (encoded by HMOX1 and HMOX2) produces endogenous carbon monoxide (CO), which is present at high levels in NES blood and has been shown to have cytoprotective effects in laboratory systems exposed to hypoxia. To understand how pathways associated with endogenous CO production and signaling change across ontogeny in diving mammals, we measured muscle CO and baseline expression of 17 CO-related genes in skeletal muscle and whole blood of three age classes of NES. Muscle CO levels approached those of animals exposed to high exogenous CO, increased with age, and were significantly correlated with gene expression levels. Muscle expression of genes associated with CO production and antioxidant defenses (HMOX1, BVR, GPX3, PRDX1) increased with age and was highest in adult females, while that of genes associated with protection from lipid peroxidation (GPX4, PRDX6, PRDX1, SIRT1) was highest in adult males. In contrast, muscle expression of mitochondrial biogenesis regulators (PGC1A, ESRRA, ESRRG) was highest in pups, while genes associated with inflammation (HMOX2, NRF2, IL1B) did not vary with age or sex. Blood expression of genes involved in regulation of inflammation (IL1B, NRF2, BVR, IL10) was highest in pups, while HMOX1, HMOX2 and pro-inflammatory markers (TLR4, CCL4, PRDX1, TNFA) did not vary with age. We propose that ontogenetic upregulation of baseline HMOX1 expression in skeletal muscle of NES may, in part, underlie increases in CO levels and expression of genes encoding antioxidant enzymes. HMOX2, in turn, may play a role in regulating inflammation related to ischemia and reperfusion in muscle and circulating immune cells. Our data suggest putative ontogenetic mechanisms that may enable phocid pups to transition to a deep-diving lifestyle, including high baseline expression of genes associated with mitochondrial biogenesis and immune system activation during postnatal development and increased expression of genes associated with protection from lipid peroxidation in adulthood.

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“…Ключовим ензимом метаболічного шляху синтезу гему є δ-амінолевулінатсинтаза (КФ 2.3.1.37), що каталізує першу реакцію біосинтетичного шляху гему -конденсацію гліцину та сукциніл-коензиму А з утворенням δ-амінолевулінової кислоти [10]. Гемоксигеназа (КФ 1.14.99.3)ключовий ензим деградації гему -забезпечує окисне розщеплення гему з утворенням в еквімолярній кількості монооксиду карбону (СО) та білівердину, що розглядаються як цитопротекторні молекули [11,12].…”

Section: вступunclassified

Cytochromes of Mitochondries and Activity of Heme Metabolism Enzymes in the Liver Under Different Nutrient Regimes

Kopylchuk¹,

Grynenkiv²,

Voloshchuk³

2021

Fiziol Zh

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The content of mitochondrial cytochromes and the activity of key enzymes of heme metabolism in the liver of rats under conditions of different dietary supply of protein and sucrose were investigated. The quantitative determination of mitochondrial cytochrome was performed by differential spectrophotometry, δ-aminolevulinate synthase activity was determined spectrophotometrically taking into account the molar extinction coefficient of 0.023x10(3) M(-1)sm(-1). Hemoxygenase activity was determined using the amount of formed bilirubin. It was found that under conditions of consumption of high-sucrose diet a significant decrease in the content of all mitochondrial cytochromes is noted: the content of cytochromes aa3, b and c1 decreases within 1.2-1.7 times, and content of cytochrome c decreases in two times. In the case of excessive consumption of sucrose on the background of alimentary protein deprivation the content of cytochromes b and c1 in the liver of rats does not differ statistically from similar indicators of the group of animals kept on a high-sucrose diet. At the same time, the content of cytochromes aa3 and c is significantly reduced. According to the activity of δ-aminolevulinate synthase under conditions of consumption of a high-sucrose diet, the studied enzymatic activity decreases by about 1.5 times with a simultaneous increase in the activity of heme oxygenase. Thus, there is a marked decrease in heme synthesis against the background of increased catabolism, which explains the decrease in the content of cytochromes in the mitochondria of the liver of rats under conditions of excess sucrose in the diet. The maximum increase in the activity of heme oxygenase (almost threefold) is observed in animals that were kept on a high-sugar diet deficient in protein content. Thus, dietary protein deficiency is a critical factor affecting the heme metabolism in the mitochondria of liver cells. The established changes in the content of mitochondrial cytochromes and the activities of key enzymes of heme metabolism in the liver could be considered as prerequisites for deepening its energy imbalance in conditions of different supply of sucrose and protein in diet.

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Heme Oxygenase 1 and 2 Differentially Regulate Glucose Metabolism and Adipose Tissue Mitochondrial Respiration: Implications for Metabolic Dysregulation

Cited by 16 publications

References 62 publications

Heme Oxygenase/Carbon Monoxide Participates in the Regulation of Ganoderma lucidum Heat-Stress Response, Ganoderic Acid Biosynthesis, and Cell-Wall Integrity

Heme Oxygenase/Carbon Monoxide Participates in the Regulation of Ganoderma lucidum Heat-Stress Response, Ganoderic Acid Biosynthesis, and Cell-Wall Integrity

Ontogeny of Carbon Monoxide-Related Gene Expression in a Deep-Diving Marine Mammal

Cytochromes of Mitochondries and Activity of Heme Metabolism Enzymes in the Liver Under Different Nutrient Regimes

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