CaMKII as a key regulator of contrast-induced nephropathy through mPTP opening in HK-2 cells
Related Experiment Video
Updated: Dec 12, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
1Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Insights
Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in contrast-induced nephropathy (CIN). Inhibiting CaMKII protects kidney tubule cells from damage caused by contrast media, offering a potential new strategy for CIN prevention.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Contrast-induced nephropathy (CIN) is a significant cause of acute kidney injury following contrast media administration.
- Current understanding of CIN pathophysiology is limited, lacking specific prevention or treatment strategies.
- Mitochondrial dysfunction and apoptosis are implicated in CIN, but the upstream regulators remain unclear.
Purpose of the Study:
- To investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in the development of CIN.
- To elucidate the molecular pathway involving CaMKII, CypD, and mitochondrial permeability transition pore (mPTP) opening in CIN.
- To explore CaMKII as a potential therapeutic target for CIN.
Main Methods:
- Utilized HK-2 cells to model CIN.
- Employing lentivirus for CypD knockdown and plasmid transfection for CaMKII overexpression.
- Assessed mitochondrial dysfunction, reactive oxygen species (ROS) production, ATP levels, lactate dehydrogenase (LDH) release, and cell apoptosis.
- Investigated the effects of CypD inhibition and CaMKII activity modulation.
Main Results:
- Iohexol treatment induced mitochondrial ROS overload, ATP depletion, LDH release, and apoptosis in HK-2 cells.
- CypD knockdown or inhibition abrogated iohexol-induced mitochondrial damage and apoptosis.
- CaMKII inhibition alleviated iohexol-induced CypD expression and subsequent mitochondrial damage and apoptosis.
- CaMKII overexpression exacerbated iohexol-induced mitochondrial damage and apoptosis.
Conclusions:
- CaMKII is a novel key player in iohexol-induced renal tubular cell apoptosis.
- The CaMKII-CypD/mPTP pathway is identified as a critical mechanism in contrast-induced tubular cell damage.
- Targeting CaMKII may offer a promising new therapeutic strategy for preventing CIN.
Abstract:
Contrast-induced nephropathy (CIN), refers to acute kidney injury observed after administration of contrast media during angiographic or other medical procedures such as urography, and accounting for 12% of all causes of acute renal failure, but no specific prevention or treatment strategy exists for its obscure pathophysiology. The aim of our study was to explore the influence of calcium/calmodulin-dependent protein kinase II (CaMKII) in CIN by using HK-2 cells. Knockdown of CypD was achieved by lentivirus, and CaMKII overexpression by transfection with the plasmid. In this study, we have demonstrated that CypD-mediated mPTP opening triggered mitochondrial dysfunction and tubule cells apoptosis in CIN. We also found that iohexol treatment was associated with mitochondrial ROS overloading, ATP depletion and LDH release. Inhibition of CypD with the pharmacologic inhibitor or knockdown of CypD abrogated mPTP opening, oxidative stress, mitochondria damage, and cell apoptosis induced by iohexol. In addition, we found that inhibition of the CaMKII activity alleviated iohexol-induced CypD expression, whereas also decreased mPTP opening, oxidative stress, mitochondria damage, and cell apoptosis, similarly to the inhibition of CypD did. Moreover, CaMKII overexpression enhanced iohexol-induced mPTP opening, mitochondrial damage and renal tubular epithelial cells apoptosis. These findings first identified the novel role of CaMKII in iohexol-induced tubular cells apoptosis and delineated the CaMKII-CypD/mPTP pathway during contrast-induced tubular cell damage. Hence, these results could provide a new strategy for CIN protection.
