Obligatory Role of Early Ca&lt;sup&gt;2+&lt;/sup&gt; Responses in H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;-Induced β-Cell Apoptosis

Sato, Takenori; Kaneko, Yukiko; Sawatani, Toshiaki; Noguchi, Atsushi; Ishikawa, Tomohisa

doi:10.1248/bpb.b15-00396

Cited by 9 publications

(11 citation statements)

References 31 publications

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“…H 2 O 2 has been shown to induce cell apoptosis, where p16 plays a crucial role616. Given a correlation between apoptosis and p16 phosphorylation was observed, we asked whether H 2 O 2 could influence the phosphorylation of p16.…”

Section: Resultsmentioning

confidence: 99%

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The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Yang

et al. 2017

Sci Rep

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Cyclin-dependent kinase inhibitor p16INK4a (p16) primarily functions as a negative regulator of the retinoblastoma protein (Rb) -E2F pathway, thus plays critical role in cell cycle progression, cellular senescence and apoptosis. In this study, we showed that the methylation of Arg 138 and the phosphorylation of Ser 140 on p16 were critical for the control of cell proliferation and apoptosis. Compared to wild type p16, mutant p16R138K possessed improved function in preventing cell proliferation and inducing apoptosis, while the Ser 140 mutation (p16S140A) exhibited the opposite alteration. We also demonstrated that H2O2 was able to induce the phosphorylation of p16, which facilitated the interaction between CDK4 (Cyclin-dependent protein kinase) and p16, in 293T (human emborynic kidney) cells. Furthermore, the elevated arginine methylation in p16S140A mutant and increased serine phosphorylation in p16R138K mutant suggest that a antagonizing mechanism coordinating Arg 138 methylation and Ser 140 phosphorylation to regulates p16 function as well as cellular apoptosis and senescence. These findings will therefore contribute to therapeutic treatment for p16-related gene therapy by providing theoretical and experimental evidence.

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Section: Resultsmentioning

confidence: 99%

“…ROS may be the first-stage initiators inducing neuron apoptosis or act as a signal in apoptotic cascade2324. As a typical ROS, hydrogen peroxide (H 2 O 2 ) is widely used as an apoptosis inducer16. It has been shown that H 2 O 2 induced DNA damage and apoptosis in human neuroblastoma SK-N-MC cells25.…”

Section: Discussionmentioning

confidence: 99%

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Yang

et al. 2017

Sci Rep

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“…Although cytosolic H 2 O 2 concentrations produced by oxidative stress in pancreatic acinar cells is not known, only small proportion of cells (34%) were response to 100 µM of H 2 O 2 and most cells (97%) were response to 300 µM of H 2 O 2 in the present study. In general, H 2 O 2 at concentrations from 10 µM to 1 mM caused intracellular Ca 2+ accumulation in various cell types [1011,12,13,14,15,16,17]. These results suggest that excess generation of oxidants in pathologic conditions could disturb Ca 2+ homeostasis mediated by sulfhydryl group oxidation in pancreatic acinar cells.…”

Section: Discussionmentioning

confidence: 98%

“…Although oxidant-induced intracellular Ca 2+ overload has been revealed in various cell types, the underlying mechanisms of Ca 2+ mobilization and elimination are complicated [1011,12,13,14,15,16,1718]. It has been known that the involvement of oxidants in Ca 2+ homeostasis is mediated by the modification of disulfide bonds between cysteine residues of Ca 2+ regulating proteins including SERCA, PMCA and Na + /Ca 2+ exchanger (NCX) [3132].…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism of H 2 O 2 -induced Ca 2+ accumulation has known to be complicated due to cell-to-cell difference in expression and participation of Ca 2+ modulating transporters. It has been reported that H 2 O 2 can enhance Ca 2+ release from intracellular store [101112], stimulate Ca 2+ entry from extracellular medium [13141516], and attenuate Ca 2+ extrusion by plasma membrane Ca 2+ ATPase (PMCA) or sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) inactivation [1718] in various cell types.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen peroxide attenuates refilling of intracellular calcium store in mouse pancreatic acinar cells

Yoon

Kim

et al. 2017

Korean J Physiol Pharmacol

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Intracellular calcium (Ca2+) oscillation is an initial event in digestive enzyme secretion of pancreatic acinar cells. Reactive oxygen species are known to be associated with a variety of oxidative stress-induced cellular disorders including pancreatitis. In this study, we investigated the effect of hydrogen peroxide (H2O2) on intracellular Ca2+ accumulation in mouse pancreatic acinar cells. Perfusion of H2O2 at 300 µM resulted in additional elevation of intracellular Ca2+ levels and termination of oscillatory Ca2+ signals induced by carbamylcholine (CCh) in the presence of normal extracellular Ca2+. Antioxidants, catalase or DTT, completely prevented H2O2-induced additional Ca2+ increase and termination of Ca2+ oscillation. In Ca2+-free medium, H2O2 still enhanced CCh-induced intracellular Ca2+ levels and thapsigargin (TG) mimicked H2O2-induced cytosolic Ca2+ increase. Furthermore, H2O2-induced elevation of intracellular Ca2+ levels was abolished under sarco/endoplasmic reticulum Ca2+ ATPase-inactivated condition by TG pretreatment with CCh. H2O2 at 300 µM failed to affect store-operated Ca2+ entry or Ca2+ extrusion through plasma membrane. Additionally, ruthenium red, a mitochondrial Ca2+ uniporter blocker, failed to attenuate H2O2-induced intracellular Ca2+ elevation. These results provide evidence that excessive generation of H2O2 in pathological conditions could accumulate intracellular Ca2+ by attenuating refilling of internal Ca2+ stores rather than by inhibiting Ca2+ extrusion to extracellular fluid or enhancing Ca2+ mobilization from extracellular medium in mouse pancreatic acinar cells.

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Jiao-tai-wan and its effective component-berberine improve diabetes and depressive disorder through the cAMP/PKA/CREB signaling pathway

Tang,

Gao,

Nie

et al. 2024

Journal of Ethnopharmacology

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Obligatory Role of Early Ca<sup>2+</sup> Responses in H<sub>2</sub>O<sub>2</sub>-Induced β-Cell Apoptosis

Cited by 9 publications

References 31 publications

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

The interplay between p16 serine phosphorylation and arginine methylation determines its function in modulating cellular apoptosis and senescence

Hydrogen peroxide attenuates refilling of intracellular calcium store in mouse pancreatic acinar cells

Jiao-tai-wan and its effective component-berberine improve diabetes and depressive disorder through the cAMP/PKA/CREB signaling pathway

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