Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy.

ABSTRACT: S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. In the present study, we found that inhibition of SAHH by using its inhibitor adenosine dialdehyde (ADA) accumulates intracellular or plasma SAH levels and increases high glucose-induced podocyte injury and aggravates STZ-induced diabetic nephropathy, which is associated with Nod-like receptor protein 3 (NLRP3) inflammasome activation. Inhibition or knockout of NLRP3 attenuates SAHH inhibition-aggravated podocyte injury and diabetic nephropathy. Additionally, SAHH inhibition increases thioredoxin-interacting prote

SUBMITTER: Dai X 

PROVIDER: S-EPMC8209273 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature