scholarly journals The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating L-Proline and Downstream Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Huiying Li ◽  
Lei Xing ◽  
Muchen Zhang ◽  
Jiaqi Wang ◽  
Nan Zheng
Keyword(s):  
Oxidative Stress ◽  
Aflatoxin B1 ◽  
Relative Concentration ◽  
Toxic Effects ◽  
Aflatoxin M1 ◽  
Mice Model ◽  
Hek 293 ◽  
Treatment Groups ◽  
Protein Levels ◽  
293 Cells

The toxic effects and potential mechanisms of aflatoxin B1 (AFB1), aflatoxin M1 (AFM1), and AFB1+AFM1 in the kidney were studied and compared in HEK 293 cells model and CD-1 mice model. The 35-day subacute toxicity mice model was constructed, biochemical indicators and kidney pathological staining were detected, kidney metabonomics detection was performed, and the metabolites were analyzed, and then the related toxicity mechanism was validated. Results showed that AFB1 (0.5 mg/kg), AFM1 (3.5 mg/kg), and AFB1 (0.5 mg/kg)+AFM1 (3.5 mg/kg) activated oxidative stress and caused renal damage. The relative concentration of the metabolite L-proline was found to be lower in aflatoxins treatment groups when compared with the control (P<0.05). Moreover, with the treatment of aflatoxins, proline dehydrogenase (PRODH) and proapoptotic factors (Bax, Caspase-3) were upregulated, while the inhibitor of apoptosis Bcl-2 was downregulated, at both the mRNA and the protein levels, comparing with the control (P<0.05). In addition, the combined effect of AFB1 and AFM1 was validated, for the toxicity of the combination was stronger than the other two groups. In conclusion, AFB1 and AFM1 caused kidney toxicity by activating oxidative stress through altering expression of PRODH and L-proline levels, which then induced downstream apoptosis.

scholarly journals The E3 Ubiquitin Ligase TEB4 Mediates Degradation of Type 2 Iodothyronine Deiodinase

2009 ◽  
Vol 29 (19) ◽  
pp. 5339-5347 ◽  
Author(s):  
Ann Marie Zavacki ◽  
Rafael Arrojo e Drigo ◽  
Beatriz C. G. Freitas ◽  
Mirra Chung ◽  
John W. Harney ◽  
...  
Keyword(s):  
Cell Types ◽  
Iodothyronine Deiodinase ◽  
Hek 293 ◽  
Protein Levels ◽  
Hematopoietic Lineage ◽  
293 Cells ◽  
Brown Adipose ◽  
Critical Instability ◽  
Proteasomal Inhibitor

ABSTRACT The endoplasmic reticulum resident thyroid hormone-activating type 2 deiodinase (D2) is inactivated by ubiquitination via the hedgehog-inducible WSB-1. Ubiquitinated D2 can then be subsequently taken up by the proteasomal system or be reactivated by USP-33/20-mediated deubiquitination. Given that heterologously expressed D2 accumulates in Saccharomyces cerevisiae lacking the E3 ligase Doa10, we tested whether the human Doa10 ortholog, TEB4, plays a role in D2 ubiquitination and degradation. In a setting of transient coexpression in HEK-293 cells, TEB4 and D2 could be coimmunoprecipitated, and additional TEB4 expression decreased D2 activity by ∼50% (P < 0.05). A highly efficient TEB4 knockdown (>90% reduction in mRNA and protein levels) decreased D2 ubiquitination and increased D2 activity and protein levels by about fourfold. The other activating deiodinase, D1, or a truncated D2 molecule (Δ18-D2) that lacks a critical instability domain was not affected by TEB4 knockdown. Furthermore, TEB4 knockdown prolonged D2 activity half-life at least fourfold, even under conditions known to promote D2 ubiquitination. Neither exposure to 1 μM of the proteasomal inhibitor MG132 for 24 h nor RNA interference WSB-1 knockdown resulted in additive effects on D2 expression when combined with TEB4 knockdown. Similar results were obtained with MSTO-211 cells, which endogenously express D2, after TEB4 knockdown using a lentivirus-based transduction strategy. While TEB4 expression predominates in the hematopoietic lineage, both WSB-1 and TEB4 are coexpressed with D2 in a number of tissues and cell types, except the thyroid and brown adipose tissue, where TEB4 expression is minimal. We conclude that TEB4 interacts with and mediates loss of D2 activity, indicating that D2 ubiquitination and degradation can be tissue specific, depending on WSB-1 and TEB4 expression levels.

Phytochemical profiling and screening of protective effects of Artabotrys odoratissimus on H2O2 induced oxidative stress in HEK-293 cells and erythrocytes

2020 ◽  
Vol 167 (4) ◽  
pp. 471-484
Author(s):  
Meghana Pargi ◽  
Sandeep Kumar Jain Raviraj ◽  
Prashanth Narayanappa ◽  
Kumaraswamy Malleshappa Honnenahally
Keyword(s):  
Oxidative Stress ◽  
Protective Effects ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells

Effect of Curcumin on Cisplatin- and Oxaliplatin-Induced Oxidative Stress in Human Embryonic Kidney (HEK) 293 Cells

Renal Failure ◽  
2011 ◽  
Vol 33 (5) ◽  
pp. 518-523 ◽  
Author(s):  
Mostafa I. Waly ◽  
Mansour S. Al Moundhri ◽  
Badreldin H. Ali
Keyword(s):  
Oxidative Stress ◽  
Human Embryonic Kidney ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells

scholarly journals PAPOLA contributes to Cyclin D1 mRNA alternative polyadenylation and promotes breast cancer cells proliferation

2021 ◽  
pp. jcs.252304
Author(s):  
Chrysoula Komini ◽  
Irini Theohari ◽  
Andromachi Lambrianidou ◽  
Lydia Nakopoulou ◽  
Theoni Trangas
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Alternative Polyadenylation ◽  
Hek 293 ◽  
Protein Levels ◽  
293 Cells ◽  
Candidate Target ◽  
Mcf 7

Poly(A) polymerases add the poly(A) tail at the 3’ end of nearly all eukaryotic mRNA, are associated with proliferation and cancer. To elucidate the role of the most studied mammalian poly(A) polymerase α (PAPOLA) in cancer, we assessed its expression in 221 breast cancer samples and found it to correlate strongly with the aggressive triple-negative subtype. Silencing PAPOLA in MCF-7 and MDA-MB-231 breast cancer cells reduced proliferation and anchorage-independent growth by decreasing steady-state CCND1 mRNA and protein levels. Whereas the length of the CCND1 mRNA poly(A) tail was not affected, its 3' untranslated region (3'UTR) lengthened. Overexpressing PAPOLA caused CCND1 mRNA 3'UTR shortening with a concomitant increase in the corresponding transcript and protein, resulting in growth arrest in MCF-7 cells and DNA damage in HEK-293 cells, whereas in the P53 mutant MDA-MB-231 promoted proliferation.Our data suggest PAPOLA as a possible candidate target for the control of tumor growth, mostly relevant to triple-negative tumors, a group characterized by its overexpression and lacking alternative targeted therapies.

scholarly journals Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1268
Author(s):  
Shahid Ali Rajput ◽  
Aftab Shaukat ◽  
Kuntan Wu ◽  
Imran Rashid Rajput ◽  
Dost Muhammad Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Aflatoxin B1 ◽  
Physiological Saline ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

Transfer of aflatoxins from naturally contaminated feed to milk of Nili-Ravi buffaloes fed a mycotoxin binder

2016 ◽  
Vol 56 (10) ◽  
pp. 1637 ◽  
Author(s):  
N. Aslam ◽  
I. Rodrigues ◽  
D. M. McGill ◽  
H. M. Warriach ◽  
A. Cowling ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
High Performance ◽  
Mean Value ◽  
Aflatoxin M1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Treatment Groups ◽  
Low Concentrations ◽  
Daily Concentration ◽  
The Mean ◽  
Carry Over

The objectives of this study were to observe the extent of transfer of aflatoxin B1 in feed to the aflatoxin M1 metabolite in milk in Nili-Ravi buffaloes and to evaluate the efficacy of a commercial mycotoxin binder (Mycofix, Biomin Singapore) incorporated into feed to minimise this transfer. Multiparous animals (n = 28) were randomly distributed to four groups corresponding to two treatments each with two levels of aflatoxin B1. Individual animals were exposed to naturally contaminated feed providing a total of 1475 µg/day (Groups A and B) or 2950 µg/day (Groups C and D) of aflatoxin B1. Groups B and D were given 50 g of mycotoxin binder daily mixed with feed whereas Groups A and C were kept as controls. Feed samples were analysed by reverse phase high performance liquid chromatography for aflatoxin B1 and milk samples were evaluated by enzyme-linked immunosorbent assay for the liver metabolite aflatoxin M1. The mean value of total daily aflatoxin M1 excretion for animals fed 2950 µg/day of aflatoxin B1 (112.6 µg/day) was almost double (P < 0.001) than the excretion in buffaloes fed 1475 µg/day (62.2 µg/day). The mean daily concentration of aflatoxin M1 in milk of animals from both treatment groups supplemented with 50 g/day of mycotoxin binder was 76.5 µg/day, nearly 22 µg lower than those without binder at 98.3 µg/day (s.e.d. = 5.99: P < 0.01). The interaction of binder and treatment was not significant i.e. the 50 g/day of binder was able to sequester aflatoxin B1 with the same efficiency in groups fed with high and low concentrations of aflatoxin B1. Carry over was (3.44%) lower (P = 0.001) in animals supplemented with 50 g/day of mycotoxin binder than those fed no binder (4.60%). Thus buffaloes are highly efficient at transferring aflatoxins in feed to the aflatoxin M1 metabolite in milk, whereas mycotoxin binder is capable of alleviating without preventing this contamination risk.

Sign in / Sign up

Export Citation Format

Share Document