Peptides GWN and GW protect kidney cells against Dasatinib induced mitochondrial injury in a SIRT1 dependent manner

Khushwant S Bhullar; Fatemeh Ashkar; Jianping Wu

doi:10.1016/j.fochms.2021.100069

Peptides GWN and GW protect kidney cells against Dasatinib induced mitochondrial injury in a SIRT1 dependent manner

Food Chem (Oxf). 2021 Dec 27:4:100069. doi: 10.1016/j.fochms.2021.100069. eCollection 2022 Jul 30.

Authors

Khushwant S Bhullar^{1

2}, Fatemeh Ashkar¹, Jianping Wu¹

Affiliations

¹ Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
² Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.

Abstract

Dasatinib, a small-molecule drug used as a treatment for chronic myeloid leukemia induces mitochondrial damage in embryonic kidney (293 T) cells (p < 0.05). This dasatinib induced mitochondrial injury in kidney cells was mitigated by H3K36me3 activating ovotransferrin-derived peptides GWN and GW. Pre-treatment of kidney cells with GWN and GW lead to elevation of cytoprotective sirtuins, SIRT1 and SIRT3, in response to dasatinib injury (p < 0.01) in vitro. Both peptides, GWN and GW, also reversed dasatinib induced the loss of mitochondria in kidney cells and promoted the protein expression of COX4 (p < 0.01). Mechanistically, loss of SIRT1 in kidney cells abolished the ability of GWN and GW to protect embryonic kidney cells against dasatinib injury in vitro. Overall, we provide cell based evidence showing that GWN and GW exhibit the ability to protect mitochondria against dasatinib-induced mitochondrial damage in a SIRT1 dependent manner.

Keywords: Dasatinib; H3K36me3; Kidneys; Mitochondria; Peptides; SIRT1.