Enhanced phosphorylation of AMPK by lutein and oxidised lutein that lead to mitochondrial biogenesis in hyperglycemic HepG2 cells

Abstract

The stimulation of adenosine monophosphate‐activated protein kinase (AMPK) is a prime target to decrease the hyperglycemic condition, hence it is a lutein (L) and oxidised lutein (OXL) is a target molecule for the treatment of type II diabetes. In the current study, a plausible interaction of L and OXL with AMPK was investigated by molecular docking. In addition, the effect of L and OXL for the activation of AMPK that triggers the downstream regulator peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), TFAM expression, mitochondrial DNA (mtDNA), mitochondrial biogenesis and superoxide dismutase 2 (SOD2) in high glucose treated HepG2 cells were investigated by quantitative polymerase chain reaction and Western blot analysis. Molecular docking reveals higher binding affinity of L (ΔG = −6.3 kcal/mol) and OXL (ΔG = −15.5 kcal/mol) with AMPK, compared with metformin (ΔG = −5.0 kcal/mol). The phosphorylation of AMPK increased by 1.3‐ and 1.5‐fold with L and OXL treatment, respectively, in high glucose induced HepG2 cells. The activation of PGC‐1α is significant (P < 0.05) in OXL group than L. Similarly, TFAM expression is increased with L and OXL compared with the high glucose group. Further increase in SOD2 and mtDNA, confirms the efficacy of L and OXL in restoring the mitochondrial biogenesis in high glucose induced cells through AMPK, PGC‐1α, and TFAM.

trans‐ferulic acid attenuates hyperglycemia‐induced oxidative stress and modulates glucose metabolism by activating AMPK signaling pathway in vitro

“…High glucose induces oxidative stress and has an implication on cellular functions and diabetes, we conducted all our experiments under high glucose (25 mM) condition and a decrease in phosphorylation of AMPK α subunit was observed in HG condition while AMPK phosphorylation was retained at the basal level under normal physiological glucose condition in both the cells, which supports earlier findings (Lee et al, 2013;Nanjaiah & Vallikannan, 2019;Shatoor et al, 2021;Shrikanth & Chilkunda, 2017). Since our aim was to identify the potential activator of AMPK for T2D, we tested the efficiency of hydroxycinnamic acid derivatives as AMPK activators under hyperglycemic condition in HepG2 and L6 cells.…”

Comparison of Antioxidant Properties of Dehydrolutein with Lutein and Zeaxanthin, and their Effects on Cultured Retinal Pigment Epithelial Cells

“…There are numerous reports showing that lutein and/or zeaxanthin can modulate expression of several antioxidant enzymes, and can activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signalling responsible for the expression of antioxidant response element (ARE) genes, and, subsequently, the synthesis of antioxidant and detoxification proteins [ 68 , 69 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. It has been reported that DMSO can activate Nrf2 [ 90 ].…”

Metformin protects diabetes-induced atrial mitochondrial from oxidative stress and improves mitochondrial biogenesis via the AMPK signaling pathway

“…28,29 It is activated in response to stress (such as hypoglycemia, hypoxia, and ischemia), which depletes intracellular ATP supply. AMPK activation leads to mitochondrial biosynthesis, 30 whereas AMPK activation is impaired in diabetes 56. 31 AMPK is the most recognized factor modulating the multiple effects of metformin.…”