Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro

Abstract

Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis.

Palmitic Acid-Induced Podocyte Apoptosis via the Reactive Oxygen Species-Dependent Mitochondrial Pathway

“…The conditionally immortalized murine podocyte clone 5 (MPC5) cell line was a kind gift from Dr. Ruan (The Centre for Nephrology, Royal Free and University College Medical School, London, United Kingdom); they were cultured as previously described [17, 18]. Briefly, cells were cultured and maintained on type I collagen-coated dishes in RPMI-1640 medium (Gibco, Karlsruhe, Germany) supplemented with 10% fetal bovine serum (Gibco), 100 U/mL penicillin, and 100 μg/mL streptomycin at two different temperatures in a 5% CO 2 incubator.…”

“…Podocyte apoptosis is one of the main risk factors causing podocyte loss [12, 16]. Our previous studies showed that palmitic acid (PA) can induce podocyte apoptosis [17, 18]. However, the precise mechanisms involved are not fully understood.…”

Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

“…In addition, the conversion of LC3 from LC3‐I to LC3‐II is a characteristic of autophagy . As indicated in Figure E, LC3‐II/LC3‐I ratio was increased in A549 and A549/Taxol cells in a time‐dependent manner after exposure to BZML.…”

“…Most studies have reported that autophagy is an important factor for apoptosis resistance . Thus, our study mainly focused on clarifying the interaction between autophagy and MC.…”

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

“…Therefore, inhibiting lysosomal degradation with CQ induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. 99 In the pancreas of individuals with type 2 diabetes, cytokine interleukin-6 (IL-6) induces autophagy and protects pancreatic beta cells from apoptosis whereas CQ causes apoptosis and thereby elicits tissue damage. 94 In contrast, inhibition of autophagy by CQ may exacerbate diabetic neuropathy and impair neuronal function.…”