l-Carnitine reduces reactive oxygen species/endoplasmic reticulum stress and maintains mitochondrial function during autophagy-mediated cell apoptosis in perfluorooctanesulfonate-treated renal tubular cells

Yuan Chii Gladys Lee, Hsiu Chu Chou, Yen Ting Chen, Szu Yu Tung, Tsui Ling Ko, Batsaikhan Buyandelger, Li Li Wen, Shu Hui Juan

Research output: Contribution to journalArticlepeer-review

Abstract

We previously reported that perfluorooctanesulfonate (PFOS) causes autophagy-induced apoptosis in renal tubular cells (RTCs) through a mechanism dependent on reactive oxygen species (ROS)/extracellular signal-regulated kinase. This study extended our findings and determined the therapeutic potency of l-Carnitine in PFOS-treated RTCs. l-Carnitine (10 mM) reversed the effects of PFOS (100 µM) on autophagy induction and impaired autophagy flux. Furthermore, it downregulated the protein level of p47Phox, which is partly related to PFOS-induced increased cytosolic ROS in RTCs. Moreover, l-Carnitine reduced ROS production in mitochondria and restored PFOS-impeded mitochondrial function, leading to sustained normal adenosine triphosphate synthesis and oxygen consumption and reduced proton leakage in a Seahorse XF stress test. The increased inositol-requiring enzyme 1α expression by PFOS, which indicated endoplasmic reticulum (ER) stress activation, was associated with PFOS-mediated autophagy activation that could be attenuated through 4-phenylbutyrate (5 mM, an ER stress inhibitor) and l-Carnitine pretreatment. Therefore, by reducing the level of IRE1α, l-Carnitine reduced the levels of Beclin and LC3BII, consequently reducing the level of apoptotic biomarkers including Bax and cleaving PARP and caspase 3. Collectively, these results indicate that through the elimination of oxidative stress, extracellular signal–regulated kinase activation, and ER stress, l-Carnitine reduced cell autophagy/apoptosis and concomitantly increased cell viability in RTCs. This study clarified the potential mechanism of PFOS-mediated RTC apoptosis and provided a new strategy for using l-Carnitine to prevent and treat PFOS-induced RTC apoptosis.

Original languageEnglish
Article number4673
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

ASJC Scopus subject areas

  • General

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