Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

SH2 domain-containing inositol 5-phosphatase (SHIP2) regulates de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells

“…Activation of PI3-K was thought to mediate the inhibition of apoB secretion possibly via the generation of the PI(3, 4, 5)P3 [33]. We have recently shown that SHIP2-WT overexpression reduces the PI3-K/Akt activity [23] and therefore it is plausible to suggest that SHIP2 may block the suppressive effect of insulin on apoB secretion by inhibiting the PI3-K/Akt activation. In addition, our data demonstrated that SHIP2 overexpression despite of a reduction in Akt activation leads to an increased expression of SREBP1c and its target genes, suggesting an Akt-independent pathway operating the lipogenic effect of SHIP2 in HepG2 cells.…”

“…A detailed description of appropriate procedure for generation of stable cells has been previously described [23]. To investigate the role of SHIP2 in lipogenesis, we performed oil red o staining in HepG2 cells at the presence of 0.5 mM Ole as an activator of lipogenesis.…”

“…Taken together, these studies demonstrate that the alterations of SHIP2 expression and/or enzymatic function appear to have a profound impact on the state of glucose and energy homeostasis during the development of insulin resistance. We have recently demonstrated that SHIP2 modulation affects HepG2 cells apoptosis via regulating the Akt/ FOXO1 pathway [23]. Given the central role of Akt and FOXO1 pathways in regulating hepatocytes lipid and lipoprotein metabolism, we in the present study aimed to investigate the role of SHIP2 in hepatic de-novo lipogenesis and the secretion of apoB100 containing lipoproteins by modulating its expression in HepG2 cells.…”

SHIP2: Structure, Function and Inhibition

“…SHIP2‐expressing multiple myeloma breast cancer cells lacking SHIP1 expression, when treated with pan‐SHIP1/2 inhibitors, undergo apoptosis . Palmitate induces apoptosis in HepG2 cells; this was increased when wild‐type SHIP2 was overexpressed and decreased if SHIP2 was inhibited . In contrast, however, in other cell types the overexpression of INPPL1 has been shown to increase apoptosis.…”

PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis

“…Another study confirmed that PBX-regulating protein 1 enhances Ship2 transcription, leading to hepatic lipogenesis and steatohepatitis in mice. However, Prep1 hypomorphic heterozygous [Prep1 (i/+)] mice displayed lower SHIP2 levels, and significantly decreased serum triacylglycerol levels and the liver expression of fatty acid synthase[106]. We have discussed above the down-regulation of SHIP2 in HCV core-expressing cells, so is this down-regulation of SHIP2 the cause of lipid droplet accumulation in these cells?…”