Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules

Abstract

Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis

“…As a critical exogenous risk factor, long-term consumption of HFD will inevitably lead to abnormal elevation of serum FA levels, which are further taken by renal tubules and stored as triglyceride, leading to renal tubular ELD . Emerging studies have shown that renal tubular ELD could cause lipotoxic damage to intrinsic renal tubular cells, following a pathology typified by hyperactivation of intracellular metabolic, oxidative, and inflammatory pathways that could ultimately provoke cell death. , Recently, several bioactive polysaccharides derived from natural products have been shown in evidence-based studies to be beneficial in countering HFD-induced metabolic disorders, including renal tubular ELD, , indicating that prolonged supplementation of such natural polysaccharides may be a beneficial strategy to reduce the risk of renal tubular ELD and CKD. Previously, we reported a homogeneous tea polysaccharide, TPS3A, with a strong potential to ameliorate HFD-exposed lipid metabolism disturbances in ApoE –/– mice .…”