Astaxanthin protects mesangial cells from hyperglycemia‐induced oxidative signaling

Abstract

Astaxanthin (ASX) is a carotenoid that has potent protective effects on diabetic nephropathy in mice model of type 2 diabetes. In this study, we investigated the protective mechanism of ASX on the progression of diabetic nephropathy using an in vitro model of hyperglycemia, focusing on mesangial cells. Normal human mesangial cells (NHMCs) were cultured in the medium containing normal (5 mM) or high (25 mM) concentrations of D-glucose. Reactive oxygen species (ROS) production, the activation of nuclear transcription factors such as nuclear factor kappa B (NFkappaB) and activator protein-1 (AP-1), and the expression/production of transforming growth factor-beta 1 (TGFbeta(1)) and monocyte chemoattractant protein-1 (MCP-1) were evaluated in the presence or absence of ASX. High glucose (HG) exposure induced significant ROS production in mitochondria of NHMCs, which resulted in the activation of transcription factors, and subsequent expression/production of cytokines that plays an important role in the mesangial expansion, an important event in the pathogenesis of diabetic nephropathy. ASX significantly suppressed HG-induced ROS production, the activation of transcription factors, and cytokine expression/production by NHMCs. In addition, ASX accumulated in the mitochondria of NHMCs and reduced the production of ROS-modified proteins in mitochondria. ASX may prevent the progression of diabetic nephropathy mainly through ROS scavenging effect in mitochondria of mesangial cells and thus is expected to be very useful for the prevention of diabetic nephropathy.

Astaxanthin ameliorates heat stress-induced impairment of blastocyst development In Vitro: –astaxanthin colocalization with and action on mitochondria–

“…3). The accumulation of Ax in mitochondria has been reported in other cell and tissue types, including leukocytes [33], mesangial cells [25], liver, and muscles [45]. The result of our present study suggests the direct action of Ax on mitochondria in bovine preimplantation embryos.…”

High glucose activates PKC-ζ and NADPH oxidase through autocrine TGF-β1 signaling in mesangial cells

“…Increased production of ROS in mitochondria consequent to excessive glucose metabolism has been proposed to mediate the detrimental effects of high glucose by inhibiting glyceraldehyde-3 phosphate dehydrogenase and increasing flux through side pathways in glycolysis (23,31,38). Nevertheless, we and others have shown that NADPH oxidase is actually the predominant source of ROS in mesangial cells exposed to high glucose (16,24,63).…”

Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities

“…Another report showed that UCP2 was negatively associated with H 2 O 2 production in kidney mitochondria of diabetic rats (79). Manabe et al (208) reported that high glucose increased ROS fluorescence in human mesangial cells associated with potentially harmful cytokine expression, an effect that was blocked by astaxanthin, a carotenoid that accumulated in mitochondria. High glucose also reportedly increased H 2 O 2 production by dichlorodihydrofluorescein fluorescence in human mesangial cells (165).…”