https://www.pnas.org/content/118/51/e2114952118

https://doi.org/10.3390/antiox10071153

https://pubmed.ncbi.nlm.nih.gov/34356388

Abstract

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H 2 O 2 -induced death, an effect that was abolished in the presence of Trx1 knockdown. βHB also alleviated the H 2 O 2 -induced inhibition of mTOR and AMPK, known targets of Trx1, in a Trx1-dependent manner, suggesting that βHB potentiates Trx1 function. It has been shown that βHB is a natural inhibitor of HDAC1 and knockdown of HDAC1 upregulated Trx1 in cardiomyocytes, suggesting that βHB may upregulate Trx1 through HDAC inhibition. βHB induced Trx1 acetylation and inhibited Trx1 degradation, suggesting that βHB-induced inhibition of HDAC1 may stabilize Trx1 through protein acetylation. These results suggest that βHB potentiates the antioxidant defense in cardiomyocytes through the inhibition of HDAC1 and the increased acetylation and consequent stabilization of Trx1. Thus, modest upregulation of ketone bodies in diabetic hearts may protect the heart through the upregulation of Trx1.

------------------------------------------ Info ------------------------------------------

Open Access: True

Authors: Shin-ichi Oka - Fan Tang - Adave Chin - Guersom Ralda - Xiaoyong Xu - Chengchen Hu - Zhi Yang - Maha Abdellatif - Junichi Sadoshima -

Additional links:

https://www.mdpi.com/2076-3921/10/7/1153/pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301070

Journal of the American Chemical SocietyDOI: 10.1021/jacs.1c03234

Jan G. Felber, Lukas Zeisel, Lena Poczka, Karoline Scholzen, Sander Busker, Martin S. Maier, Ulrike Theisen, Christina Brandstädter, Katja Becker, Elias S. J. Arnér, Julia Thorn-Seshold, and Oliver Thorn-Seshold

https://ift.tt/3iemrBh

A reductive approach : A diselenide‐based probe for the detection of thioredoxin reductase 1 (TrxR1) was designed and synthesized. The non‐fluorescent probe switched on in the presence of TrxR1 and had minimal interference from other biological reducing species. The diselenide probe was successfully used in imaging TrxR1 in human lung cancer cells and showed greater fluorescence compared to a disulfide‐based analogue.

Abstract

We report the first diselenide‐based probe for the selective detection of thioredoxin reductase (TrxR), an enzyme commonly overexpressed in melanomas. The probe design involves conjugation of a seminaphthorhodafluor dye with a diselenide moiety. TrxR reduces the diselenide bond, triggering a fluorescence turn‐on response of the probe. Kinetic studies reveal favorable binding of the probe with TrxR with a Michaelis–Menten constant (Km) of 15.89 μm . Computational docking simulations predict a greater binding affinity to the TrxR active site in comparison to its disulfide analogue. In vitro imaging studies further confirmed the diselenide probe exhibited improved signaling of TrxR activity compared to the disulfide analogue.

https://ift.tt/2TBUAOh

Thanks in advance!

http://www.nature.com/clpt/journal/v78/n4/full/clpt2005512a.html

I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.

Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.

Do your worst!

I'm surprised it hasn't decade.

For context I'm a Refuse Driver (Garbage man) & today I was on food waste. After I'd tipped I was checking the wagon for any defects when I spotted a lone pea balanced on the lifts.

I said "hey look, an escaPEA"

No one near me but it didn't half make me laugh for a good hour or so!

Edit: I can't believe how much this has blown up. Thank you everyone I've had a blast reading through the replies 😂

https://www.mdpi.com/2076-3921/10/7/1153/htm

β-Hydroxybutyrate, a Ketone Body, Potentiates the Antioxidant Defense via Thioredoxin 1 Upregulation in Cardiomyocytes

by 📷Shin-ichi Oka 1,📷Fan Tang 1,📷Adave Chin 1,📷Guersom Ralda 1,📷Xiaoyong Xu 1,2,📷Chengchen Hu 1,📷Zhi Yang 1,📷Maha Abdellatif 1 and📷Junichi Sadoshima 1,*1Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA2Department of Cardiovascular Disease, Ningbo Medical Treatment Centre Li Huili Hospital, Ningbo 315000, China*Author to whom correspondence should be addressed.Academic Editor: Xavier FioramontiAntioxidants 2021, 10(7), 1153; https://doi.org/10.3390/antiox10071153 (registering DOI)Received: 14 June 2021 / Revised: 12 July 2021 / Accepted: 16 July 2021 / Published: 20 July 2021

Abstract

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H2O2-induced death, an effect that was abolished in t

We report the first diselenide‐based probe for the selective detection of thioredoxin reductase (TrxR), an enzyme commonly overexpressed in melanomas. The probe design involves conjugation of a seminaphthorhodafluor dye with a diselenide moiety. TrxR reduces the diselenide bond, triggering a fluorescence turn‐on response of the probe. Kinetic studies reveal favorable binding of the probe with TrxR with a Michaelis‐Menten constant (K m ) of 15.89 µM. Computational docking simulations predict a greater binding affinity to the TrxR active site in comparison to its disulfide analogue. In vitro imaging studies further confirmed the diselenide probe exhibited improved signaling of TrxR activity compared to the disulfide analogue.

https://ift.tt/2TBUAOh