2. Academic Validation
  3. Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes

Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes

  • Mol Biol Rep. 2021 Feb;48(2):1453-1464. doi: 10.1007/s11033-021-06204-4.
Yingjun Zang  # 1,  Shuang Liu  # 1,  Aili Cao 2,  Xiangyu Shan 1,  Wenjuan Deng 1,  Zhijun Li 1,  Hao Wang 1,  Yunman Wang 1,  Li Wang 3,  Wen Peng 4 5
Affiliations

Affiliations

  • 1 Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People's Republic of China.
  • 2 Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, People's Republic of China.
  • 3 Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, People's Republic of China. wanglitcm2007@163.com.
  • 4 Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People's Republic of China. pengwen_01@vip.sina.com.
  • 5 Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, People's Republic of China. pengwen_01@vip.sina.com.
  • # Contributed equally.
PMID: 33606151 DOI: 10.1007/s11033-021-06204-4
Abstract

Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte Apoptosis by activating sarcoendoplasmic reticulum CA2+ ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte Apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum CA2+ and elevation of cytosolic and mitochondrial CA2+. Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte Apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte Apoptosis is CA2+-dependent. And the efficacy correlates with inhibiting TRPC6-mediated CA2+ influx, and then cellular CA2+ disturbance was coordinated.

Keywords

Astragaloside IV; Calcium homeostasis; Endoplasmic reticulum stress; Podocyte apoptosis; TRPC6.

Figures
Products