cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2

Isshiki, Kinuka; Matsuda, Shinya; Tsuji, Akihiko; Yuasa, Keizo

doi:10.1016/j.bbrc.2012.04.148

Cited by 22 publications

(20 citation statements)

References 23 publications

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“…Activation of cGMP/PKG pathway inhibits breast or colon cancer cell growth and angiogenesis, and it induces these cells' apoptosis (13,27,47). A death-associated protein kinase 2 has been identified to be the substrate of PKG-I and mediates PKG-Iinduced breast cancer cell apoptosis (25). Moreover, studies showed that sildenafil may enhance the sensitivity of certain types of cancer to chemotherapeutic drugs (2,11,46).…”

Section: Discussionmentioning

confidence: 98%

Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

Maimaitiyiming

Cui

et al. 2013

American Journal of Physiology-Renal Physiology

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Cisplatin is widely used to treat malignancies. However, its major limitation is the development of dose-dependent nephrotoxicity. The precise mechanisms of cisplatin-induced kidney damage remain unclear, and the renoprotective agents during cisplatin treatment are still lacking. Here, we demonstrated that the expression and activity of cGMP-dependent protein kinase-I (PKG-I) were reduced in cisplatin-treated renal tubular cells in vitro as well as in the kidney tissues from cisplatin-treated mice in vivo. Increasing PKG activity by both pharmacological and genetic approaches attenuated cisplatin-induced kidney cell apoptosis in vitro. This was accompanied by decreased Bax/Bcl2 ratio, caspase 3 activity, and cytochrome c release. Cisplatin-induced mitochondria membrane potential loss in the tubular cells was also prevented by increased PKG activity. All of these data suggest a protective effect of PKG on mitochondria function in renal tubular cells. Importantly, increasing PKG activity pharmacologically or genetically diminished cisplatin-induced tubular damage and preserved renal function during cisplatin treatment in vivo. Mitochondria structural and functional damage in the kidney from cisplatin-treated mice was inhibited by increased PKG activity. In addition, increasing PKG activity enhanced ciaplatin-induced cell death in several cancer cell lines. Taken together, these results suggest that increasing PKG activity may be a novel option for renoprotection during cisplatin-based chemotherapy.

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Section: Discussionmentioning

confidence: 98%

Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

Maimaitiyiming

Cui

et al. 2013

American Journal of Physiology-Renal Physiology

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“…In addition to the described regulatory mechanisms, DAPK2 was recently shown to be phosphorylated by cGMP-dependent protein kinase I on S299 (Isshiki et al, 2012). Phosphorylation of S299, which lies within the CaM-binding autoregulatory domain, increased DAPK2 activity, independent of CaM binding, but by counter-acting the autoinhibitory mechanism resulting from S318 phosphorylation.…”

Section: Regulation Of Dapk2 Activitymentioning

confidence: 98%

“…Ectopic expression of wild-type DAPK2, constitutively active DAPK2 ( CaM mutant), S299D mutated DAPK2 or DRP-1␤ in adherent cells (including HEK-293, NIH-3T3, HeLa cells), results in massive membrane blebbing, partial nuclear condensation, cell rounding and partial detachment from the plate within 24 h of transfection (Inbal et al, 2000(Inbal et al, , 2002Isshiki et al, 2012;Kawai et al, 1999;Shani et al, 2001;Shoval et al, 2011), cellular features reminiscent of apoptosis. Hence, early reports -in accordance with the published DAPK1 phenotype -suggested an involvement of DAPK2 in apoptosis.…”

Section: The Ambiguous Role Of Dapk2 In the Regulation Of Apoptosismentioning

confidence: 99%

Death-associated protein kinase 2: Regulator of apoptosis, autophagy and inflammation

Geering

2015

The International Journal of Biochemistry & Cell Biology

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“…Other studies using experimental compounds that activate PKG show that even activation of PKG is sufficient to inhibit breast cell growth and induce apoptosis [54][55][56]. Unfortunately, the in vivo or clinical relevance of these findings cannot be determined due to poor pharmacodynamic, pharmacokinetic, and toxicity profiles of the compounds as a result of their lack of target specificity.…”

Section: Targeting Cgmp Signaling In Breast Cancermentioning

confidence: 91%

cGMP signaling as a target for the prevention and treatment of breast cancer

Windham

Tinsley

2015

Seminars in Cancer Biology

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cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2

Cited by 22 publications

References 23 publications

Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

Increasing cGMP-dependent protein kinase I activity attenuates cisplatin-induced kidney injury through protection of mitochondria function

Death-associated protein kinase 2: Regulator of apoptosis, autophagy and inflammation

cGMP signaling as a target for the prevention and treatment of breast cancer

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