5‐ALA/SFC enhances HO‐1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis

Liu, Chi; Fujino, Masayuki; Zhu, Shuoji; Isaka, Yoshitaka; Ito, Hidenori; Takahashi, Kiwamu; Nakajima, Motowo; Tanaka, Tohru; Zhu, Ping; Li, Xiaokang

doi:10.1002/2211-5463.12729

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…protect kidneys from acute injury [15,16]. Moreover, both in vivo and in vitro studies show that 5-ALA can induce heme oxygenase-1 (HO-1) expression in kidney cells [17,18].…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

“…Glycine, a non-essential amino acid, combines with succinyl-CoA to form 5-ALA in the presence of 5-ALA synthase as part of the heme biosynthetic pathway in animals [ 14 ]. 5-ALA can reduce nephrotoxicity and apoptosis in murine tubular epithelial cells and can protect kidneys from acute injury [ 15 , 16 ]. Moreover, both in vivo and in vitro studies show that 5-ALA can induce heme oxygenase-1 (HO-1) expression in kidney cells [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of 5-aminolevulinic acid on heat stress in bovine mammary epithelial cells

et al. 2021

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Cells have increased susceptibility to activation of apoptosis when suffering heat stress (HS). An effective supplementation strategy to mimic heat-induced apoptosis of bovine mammary epithelial cells (MECs) is necessary to maintain optimal milk production. This study aimed to investigate possible protective effects of the anti-apoptotic activity of 5-aminolevulinic acid (5-ALA) against HS-induced damage of bovine MECs. Methods: Bovine MECs were pretreated with or without 5-ALA at concentrations of 10, 100, and 500 μM for 24 h followed by HS (42.5°C for 24 h and 48 h). Cell viability was measured with MTT assays. Real-time qPCR and Western blotting were used to explore the regulation of genes associated with apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress genes. Results: We found that 5-ALA induces cytoprotection via inhibition of apoptosis markers after HS-induced damage. Pretreatment of bovine MECs with 5-ALA resulted in dramatic upregulation of mRNA for nuclear factor erythroid-derived 2-like factor 2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO1), all of which are antioxidant stress genes. Moreover, 5-ALA pretreatment significantly suppressed HS-induced ER stress-associated markers, glucose-regulated protein 78 (GRP78), and C/EBP homologous protein (CHOP) expression levels. Conclusion: 5-ALA has the ability to ameliorate the ER stress in heat stressed bovine mammary epithelial cell via enhancing the expression of antioxidant gene.

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“…protect kidneys from acute injury [15,16]. Moreover, both in vivo and in vitro studies show that 5-ALA can induce heme oxygenase-1 (HO-1) expression in kidney cells [17,18].…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effects of 5-aminolevulinic acid on heat stress in bovine mammary epithelial cells

et al. 2021

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“…HO-1 was markedly upregulated after IRI and its expression was even 1.32-fold higher in mice treated with rapamycin [ 82 ]. Moreover, HO-1 induction may have a beneficial effect on cyclosporine-mediated toxicity, through a reduction of fibrosis of proximal tubules and renal apoptosis [ 83 , 84 , 85 ]. Taken together, these studies suggest that chronic immunosuppression is responsible for cellular stress at kidney level and this may upregulate the expression of HO-1.…”

Section: Acute and Chronic Rejection And Immunosuppressionmentioning

confidence: 99%

Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

et al. 2020

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Kidney transplantation is a well-established therapy for patients with end-stage renal disease. While a significant improvement of short-term results has been achieved in the short-term, similar results were not reported in the long-term. Heme-oxygenase (HO) is the rate-limiting enzyme in heme catabolism, converting heme to iron, carbon monoxide, and biliverdin. Heme-oxygenase overexpression may be observed in all phases of transplant processes, including brain death, recipient management, and acute and chronic rejection. HO induction has been proved to provide a significant reduction of inflammatory response and a reduction of ischemia and reperfusion injury in organ transplantation, as well as providing a reduction of incidence of acute rejection. In this review, we will summarize data on HO and kidney transplantation, suggesting possible clinical applications in the near future to improve the long-term outcomes.

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“…A recent study by our group found that 5-ALA could reduce heat stress-mediated ER stress-induced apoptosis of bovine MECs [ 13 ]. 5-ALA also effectively inhibits apoptosis in response to OxS and other stressors [ 14 , 15 , 16 , 17 ]. Therefore, 5-ALA has the potential to protect bovine MECs, thereby facilitating an optimum amount of milk production.…”

Section: Introductionmentioning

confidence: 99%

5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells

et al. 2021

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The conservation of mammary gland physiology by maintaining the maximum number of mammary epithelial cells (MECs) is of the utmost importance for the optimum amount of milk production. In a state of negative energy balance, palmitic acid (PA) reduces the number of bovine MECs. However, there is no effective strategy against PA-induced apoptosis of MECs. In the present study, 5-aminolevulinic acid (5-ALA) was established as a remedial agent against PA-induced apoptosis of MAC-T cells (an established line of bovine MECs). In PA-treated cells, the apoptosis-related genes BCL2 and BAX were down- and upregulated, respectively. The elevated expression of major genes of the unfolded protein response (UPR), such as CHOP, a proapoptotic marker (C/EBP homologous protein), reduced the viability of PA-treated MAC-T cells. In contrast, 5-ALA pretreatment increased and decreased BCL2 and BAX expression, respectively. Moreover, cleaved caspase-3 protein expression was significantly reduced in the 5-ALA-pretreated group in comparison with the PA group. The downregulation of major UPR-related genes, including CHOP, extended the viability of MAC-T cells pretreated with 5-ALA and also reduced the enhanced intensity of the PA-induced expression of phospho-protein kinase R-like ER kinase. Moreover, the enhanced expression of HO-1 (antioxidant gene heme oxygenase) by 5-ALA reduced PA-induced oxidative stress (OxS). HO-1 is not only protective against OxS but also effective against ER stress. Collectively, these findings offer new insights into the protective effects of 5-ALA against PA-induced apoptosis of bovine MECs.

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5‐ALA/SFC enhances HO‐1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis

Cited by 16 publications

References 33 publications

Protective effects of 5-aminolevulinic acid on heat stress in bovine mammary epithelial cells

Protective effects of 5-aminolevulinic acid on heat stress in bovine mammary epithelial cells

Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells

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