[Effects of Cadmium on Ca2+ and IRE1 signaling pathway in GC2 spd cells]
Yue Han1, Rui Xue Zhao1, Jiao Yang Wei1
1School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
Objective:
To study the effects of cadmium on autophagy in germ cells (GC-2 spd cells) through Ca2+ and IRE1 pathway.
Methods:
The viability of GC-2 spd cells was determined using a CCK-8 assay to establish the concentration of cadmium treating . MDC staining was employed to assess autophagosome formation. Laser confocal microscopy and flow cytometry were utilized to measure cytoplasmic and endoplasmic reticulum (ER) Ca2+ levels. Western blot was conducted to evaluate the expression levels of proteins associated with the IRE1 signaling pathway and autophagy.
Results:
As the concentration of cadmium increased, cell viability gradually decreased. The concentrations of cadmium were determined to be 2.5, 5, and 10 μmol/L. Compared with the control group, the IOD values of MDC fluorescence intensity within the cadmium group were all elevated (P<0.05), accompanied by elevated ratios of autophagy markers LC3-II/LC3-I and up-regulation of Beclin-1 protein expression (P<0.05). Cytoplasm Ca2+ levels gradually increased, while ER Ca2+ levels decreased (P<0.05). The expression of IP3R protein, the ER Ca2+ release pathway, was up-regulated (P<0.05). Additionally, the expressions of IRE1, XBP1s, CHOP, and GRP78 were up-regulated in the cadmium group (P<0.05).
Conclusion:
Cadmium exposure can induce dysregulation of calcium homeostasis in GC-2spd cells, activates the ER stress-induced IRE1 signaling pathway, and ultimately induces the occurrence of autophagy in GC-2spd cells.
Insights
Cadmium exposure disrupts calcium balance and activates the IRE1 pathway in germ cells, triggering autophagy. This study reveals cadmium
Area of Science:
- Cell Biology
- Toxicology
- Reproductive Biology
Context:
- Cadmium is a toxic heavy metal with known adverse effects on reproductive health.
- Autophagy plays a crucial role in cellular homeostasis and survival.
- Germ cell function is vital for reproduction and susceptible to environmental toxins.
Purpose:
- To investigate the impact of cadmium exposure on autophagy in germ cells (GC-2 spd cells).
- To elucidate the roles of calcium (Ca2+) signaling and the IRE1 pathway in cadmium-induced autophagy.
Summary:
- Cadmium exposure decreased GC-2 spd cell viability in a dose-dependent manner.
- Cadmium induced autophagy, evidenced by increased autophagosome formation and elevated levels of autophagy markers (LC3-II/LC3-I, Beclin-1).
- Cadmium disrupted calcium homeostasis, increasing cytoplasmic Ca2+ and decreasing endoplasmic reticulum (ER) Ca2+ levels, while up-regulating the IP3R pathway.
- The study observed activation of the ER stress-induced IRE1 signaling pathway (IRE1, XBP1s, CHOP, GRP78) in response to cadmium.
Impact:
- This research clarifies the mechanisms by which cadmium induces autophagy in germ cells.
- Understanding the interplay between calcium, ER stress, and autophagy provides insights into cadmium's reproductive toxicity.
- Findings may inform strategies to mitigate cadmium-induced damage to germ cells.
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