Deletion of the Kinase Domain in Death-Associated Protein Kinase Attenuates Tubular Cell Apoptosis in Renal Ischemia-Reperfusion Injury

Kishino, Masanori; Yukawa, Kazunori; Hoshino, Katsuaki; Kimura, Akihiko; Shirasawa, Nobuyuki; Otani, Haruhisa; Tanaka, Tetsuji; Owada-Makabe, Kyoko; Tsubota, Yuji; Maeda, Masanobu; Ichinose, Masakazu; Takeda, Kiyoshi; Akira, Shizuo; Mune, Masatoshi

doi:10.1097/01.asn.0000131527.59781.f2

Cited by 25 publications

(23 citation statements)

References 50 publications

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“…16 The significant decline in apoptotic rate observed by 7 d, conversely, is consistent with its marked fall observed after the first days after IR. 35 The initial increase of p21 expression at 48 h after IR and its significant decline at 7 d in WTs are consistent with another mouse model of renal IR injury, 36 revealing a normal p21 upregulation shortly after this insult, followed by a return to preinjury levels within the next days. This course in WT kidneys, associated with nonincreased p21 expression at 48 h in HTs, indicates that Pkd1-haploinsufficient mice are unable to upregulate p21 early after the IR insult.…”

Section: Discussionsupporting

confidence: 62%

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Bastos

Piontek

Silva

et al. 2009

Journal of the American Society of Nephrology

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Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10-to 12-wk-old male noncystic Pkd1 ϩ/Ϫ and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploinsufficient mice, a process that apparently depends on a relative deficiency of p21 activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury.

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Section: Discussionsupporting

confidence: 62%

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Bastos

Piontek

Silva

et al. 2009

Journal of the American Society of Nephrology

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“…DAPK-mutant mice expressing a mutant form of DAPK lacking the kinase domain (amino acids 22-95) were generated as described previously (16)(17)(18)(19). The mutant mice had a C57BL/6 genetic background, and wild-type littermates were used as controls.…”

Section: Methodsmentioning

confidence: 99%

“…Both the kinase domain and death domain are critical for its death-mediating functions (8,14,15). Using DAPK-mutant mice lacking the 74-amino acid catalytic kinase domain of DAPK, we have revealed that DAPK plays a pro-apoptotic role in renal tubular cell apoptosis in chronic obstructive uropathy and renal ischemiareperfusion injuries (16)(17)(18). Furthermore, DAPK is involved in modulating spatial memory in mice (19).…”

Section: Introductionmentioning

confidence: 99%

Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase

Tanaka²,

Yukawa³

et al. 2009

Int J Oncol

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Abstract. Although death-associated protein kinase (DAPK) is a Ca2+ /calmodulin-regulated serine/threonine kinase that plays important roles in various types of apoptotic cell death, there have been no reports of its tissue distributions and functions in female reproductive organs. By comparing C57BL/6 wild-type mice with DAPK-mutant mice lacking the 74-amino acid catalytic kinase domain of DAPK, the cellular distributions and biological functions of DAPK in murine ovaries were investigated. In situ hybridization analyses with sense and antisense riboprobes revealed that DAPK mRNA was selectively and highly expressed in granulosa cells in the ovaries of both types of mice. There were no significant differences in the body weights, ovarian weights and unstimulated ovarian follicular numbers between the wild-type and DAPK-mutant mice. Intraperitoneal injection of CPT-11, an anticancer topoisomerase I inhibitor that causes granulosa cell-specific apoptosis partly through Fas-Fas ligand (FasL) interactions in MCH mice, induced follicular apoptosis in both the wild-type and DAPK-mutant mice. However, the numbers of apoptotic follicles were significantly reduced in the DAPK-mutant mice. The Fas and FasL expression levels in the CPT-11-injected mice did not differ significantly between the wild-type and DAPK-mutant mice. These results indicate that DAPK positively regulates intracellular signaling pathways for CPT-11-induced granulosa cell apoptosis.

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“…DAPK is known to modulate apoptosis induced by several cytokines, Fas, ceramide, and cellular detachment from the extracellular matrix (4-7). Studies using knockout mice revealed crucial roles of DAPK in apoptotic cell death induced in vitro and in vivo (5,(8)(9)(10)(11). Thus, many studies, including ours, showed that DAPK was linked to apoptosis, by disclosing its pro-apoptotic role.…”

Section: Introductionmentioning

confidence: 99%

“…Mice expressing a mutant form of DAPK lacking a portion of the kinase domain (amino acids 22-95), were generated by gene targeting in E14.1 embryonic stem (ES) cells (8)(9)(10)(11). Briefly, targeting vectors were designed to replace the exon encoding amino acids 22-95 of mature DAPK with a neomycin-resistance gene.…”

Section: Dapk-mutant Micementioning

confidence: 99%

Deletion of the kinase domain from death-associated protein kinase enhances spatial memory in mice

Yukawa

Tanaka²,

Bai³

et al. 2006

Int J Mol Med

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Abstract. Death-associated protein kinase (DAPK) is a Ca 2+ /calmodulin-dependent serine/threonine kinase that is thought to mediate apoptosis. DAPK is highly expressed in hippocampal neurons which are essential elements for memory formation. To examine if DAPK is implicated in spatial learning and memory, both wild-type and DAPK-mutant mice were subjected to Morris water maze tests. DAPKmutant mice were generated by deleting 74 amino acids from the catalytic kinase domain of DAPK, and were used to investigate roles of the DAPK kinase domain in regulating spatial memory. Both mutant and wild-type mice were able to learn the water maze tasks to locate a hidden escape platform. In the first probe test, mutant mice showed a more precise memory for platform position compared to wild-type mice. In the reversal training in which the platform was located opposite from the original position, DAPK-mutant mice exhibited superior spatial learning compared to wildtype mice. DAPK-mutant mice also showed a more precise memory than their wild-type littermates in the probe trial of reversal test. Thus, the present results revealed crucial implications of DAPK in regulating spatial memory in mice.

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Deletion of the Kinase Domain in Death-Associated Protein Kinase Attenuates Tubular Cell Apoptosis in Renal Ischemia-Reperfusion Injury

Cited by 25 publications

References 50 publications

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Irinotecan-induced ovarian follicular apoptosis is attenuated by deleting the kinase domain of death-associated protein kinase

Deletion of the kinase domain from death-associated protein kinase enhances spatial memory in mice

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