scholarly journals Progressive obesity alters ovarian insulin, phosphatidylinositol-3 kinase, and chemical metabolism signaling pathways and potentiates ovotoxicity induced by phosphoramide mustard in mice†

2017 ◽  
Vol 96 (2) ◽  
pp. 478-490 ◽  
Author(s):  
Jackson Nteeba ◽  
Shanthi Ganesan ◽  
Jill A. Madden ◽  
Mackenzie J. Dickson ◽  
Aileen F. Keating
Keyword(s):  
Signaling Pathways ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphoramide Mustard ◽  
Phosphatidylinositol 3

Possibility of distinct insulin-signaling pathways beyond phosphatidylinositol 3-kinase-mediating glucose transport and lipogenesis

Diabetes ◽  
1998 ◽  
Vol 47 (2) ◽  
pp. 179-185 ◽  
Author(s):  
R. W. Stevenson ◽  
D. K. Kreutter ◽  
K. M. Andrews ◽  
P. E. Genereux ◽  
E. M. Gibbs
Keyword(s):  
Signaling Pathways ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Parallel Phosphatidylinositol-3 Kinase and p42/44 Mitogen-Activated Protein Kinase Signaling Pathways Subserve the Mitogenic and Antiapoptotic Actions of Insulin-Like Growth Factor I in Osteoblastic Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4886-4893 ◽  
Author(s):  
Andrew Grey ◽  
Qi Chen ◽  
Xin Xu ◽  
Karen Callon ◽  
Jill Cornish
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Osteoblastic Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
P70s6 Kinase ◽  
Igf I ◽  
Convergence Point ◽  
Phosphatidylinositol 3

Abstract IGF-I is an endocrine and paracrine regulator of skeletal homeostasis, principally by virtue of its anabolic effects on osteoblastic cells. In the current study, we examined the intracellular signaling pathways by which IGF-I promotes proliferation and survival in SaOS-2 human osteoblastic cells. Inhibition of each of the phosphatidylinositol-3 kinase (PI-3 kinase), p42/44 MAPK, and p70s6 kinase pathways partially inhibited the ability of IGF-I to stimulate osteoblast proliferation and survival. Because activation of p70s6 kinase is downstream of both PI-3 kinase and p42/44 MAPK activation in osteoblasts treated with IGF-I, this ribosomal kinase represents a convergence point for IGF-I-induced PI-3 kinase and p42/44 MAPK signaling in osteoblastic cells. In addition, abrogation of PI-3 kinase-dependent Akt signaling, which does not inhibit IGF-I-induced p70s6 kinase phosphorylation, also inhibited the antiapoptotic effects of IGF-I in osteoblasts. Finally, interruption of Gβγ signaling partially abrogated the ability of IGF-I to promote osteoblast survival, without inhibiting signaling through PI-3 kinase/Akt, p42/44 MAPKs, or p70s6 kinase. These data suggest that IGF-I signals osteoblast mitogenesis and survival through parallel, partly overlapping intracellular pathways involving PI-3 kinase, p42/44 MAPKs, and Gβγ subunits.

scholarly journals Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

2003 ◽  
pp. 147-155 ◽  
Author(s):  
S Kang ◽  
J Song ◽  
H Kang ◽  
S Kim ◽  
Y Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Pi3 Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Extracellular Signal ◽  
Apoptotic Activity ◽  
Phosphatidylinositol 3

OBJECTIVE: Insulin has well-known activities in controlling energy metabolism, cellular proliferation and biosynthesis of functional molecules to maintain a biological homeostasis. Recently, several studies have suggested that insulin may protect cells from apoptosis in different cell lines; however, little is known about the nature of its anti-apoptotic activity. In many clinical disorders, including type 2 diabetes mellitus, oxidative stress and the production of reactive oxygen species (ROS) is increased. With these facts as a background, we examined here whether insulin protects HepG2 cells from apoptosis by decreasing oxidative stress and, if so, which signaling steps are involved in this process. METHODS: Intracellular DNA content, the degree of nuclear condensation or poly(ADP-ribose) polymerase hydrolysis was measured to verify the occurrence of apoptotic events. Caspase-3 activity and ROS accumulation within cells were also measured. Western blot analysis was performed to identify signaling molecules activated in response to insulin. RESULTS: Serum starvation resulted in a marked accumulation of ROS, activation of caspase-3, and subsequent apoptotic cell death which were, in turn, markedly blocked by the addition of insulin. The anti-apoptotic activity of insulin was sensitive to blockade of two different signaling steps, activations of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated protein kinase (ERK). CONCLUSION: Insulin exerts an anti-apoptotic activity by suppressing the excessive accumulation of ROS within cells through signaling pathways including stimulation of PI3 kinase and ERK in HepG2 cells.

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs

2021 ◽  
pp. 107815522110353
Author(s):  
Mahshid Mehdizadeh ◽  
Behrouz Farhadihosseinabadi ◽  
Maryam Nikoonezhad ◽  
Ghazaleh Sankanian ◽  
Masoud Soleimani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Small Molecules ◽  
Signaling Pathways ◽  
High Rate ◽  
Kinase Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Signaling Inhibitors ◽  
Effective Drugs ◽  
Phosphatidylinositol 3

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.

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