Details

Autor(en) / Beteiligte

• Wisessaowapak, Churaibhon
• Niyomchan, Apichaya
• Visitnonthachai, Daranee
• Leelaprachakul, Naphada
• Watcharasit, Piyajit
• Satayavivad, Jutamaad

Titel

Arsenic‐induced IGF‐1 signaling impairment and neurite shortening: The protective roles of IGF‐1 through the PI3K/Akt axis

Ist Teil von

• Environmental toxicology, 2024-03, Vol.39 (3), p.1119-1128

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• We recently reported that arsenic caused insulin resistance in differentiated human neuroblastoma SH‐SY5Y cells. Herein, we further investigated the effects of sodium arsenite on IGF‐1 signaling, which shares downstream signaling with insulin. A time‐course experiment revealed that sodium arsenite began to decrease IGF‐1‐stimulated Akt phosphorylation on Day 3 after treatment, indicating that prolonged sodium arsenite treatment disrupted the neuronal IGF‐1 response. Additionally, sodium arsenite decreased IGF‐1‐stimulated tyrosine phosphorylation of the IGF‐1 receptor β (IGF‐1Rβ) and its downstream target, insulin receptor substrate 1 (IRS1). These results suggested that sodium arsenite impaired the intrinsic tyrosine kinase activity of IGF‐1Rβ, ultimately resulting in a reduction in tyrosine‐phosphorylated IRS1. Sodium arsenite also reduced IGF‐1 stimulated tyrosine phosphorylation of insulin receptor β (IRβ), indicating the potential inhibition of IGF‐1R/IR crosstalk by sodium arsenite. Interestingly, sodium arsenite also induced neurite shortening at the same concentrations that caused IGF‐1 signaling impairment. A 24‐h IGF‐1 treatment partially rescued neurite shortening caused by sodium arsenite. Moreover, the reduction in Akt phosphorylation by sodium arsenite was attenuated by IGF‐1. Inhibition of PI3K/Akt by LY294002 diminished the protective effects of IGF‐1 against sodium arsenite‐induced neurite retraction. Together, our findings suggested that sodium arsenite‐impaired IGF‐1 signaling, leading to neurite shortening through IGF‐1/PI3K/Akt.