Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Abstract

Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury. Am J Physiol Renal Physiol 302: F561-F570, 2012. First published December 7, 2011 doi:10.1152/ajprenal.00355.2011.-cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/ activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG

Investigation of the role of nitric oxide/soluble guanylyl cyclase pathway in ascorbic acid-mediated protection against acute kidney injury in rats

“…The present study observed renal damage with methylene blue thus justifying importance of sGC in renal IRI. Similarly, an increase in cGMP-dependent protein kinase I level has been documented to be protective against IRI-induced renal injury [12].…”

“…The NO activates sGC that converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP) which in turn causes smooth muscle relaxation and vasodilatation. The role of cGMP has been explored in various models of renal dysfunction and increase in its level has been documented to be protective against IRI and cisplatin-induced renal injury [12].…”

C-type natriuretic peptide ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting apoptosis and oxidative stress in rats

“…Overexpression of cGMP-dependent protein kinase I could protect against IR-induced kidney injury by inhibiting inflammation and tubular cell apoptosis (Li et al, 2012). Similarly, NO-cGMP (Choi et al, 2009) and NPR-cGMP signaling pathways (De Vito et al, 2010;Ogawa et al, 2012) are also known to protect IR injury by inhibiting apoptosis and oxidative stress.…”

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

“…PKG-I has numerous effects on the vessel wall such as vasodilation, vascular permeability, induction of platelet aggregation, and regulation of smooth muscle cell proliferation (20,30,32,45). In addition to regulating vessel wall function, our previous studies demonstrate a renal protective effect of PKG-I activation on diabetes or ischemia-reperfusion-induced kidney injury (29,52). Recently, numerous studies suggest an anti-tumor effect of cGMP/PKG signaling, including induction of tumor cell apoptosis and inhibition of metastasis (13,15,16,27,47).…”

“…Results were normalized by 18S. Relative mRNA expression was calculated using the MyiQ system software as previously reported (29). 2) To quantify mitochondria DNA copy number, DNA was extracted from freshly frozen kidney tissues by using QIAamp DNA mini kit (Qiagen).…”