TRPM7 is involved in acid ‐induced necrotic cell death in a manner sensitive to progesterone in human cervical cancer cells

Progesterone treatment was surprisingly found to suppress the molecular and functional expression of TRPM7 and cell proliferation in HeLa cells. Furthermore, in progesterone ‐treated cells, acid exposure did not induce persistent cell swelling and subsequent necrosis, but induced persistent cell shrinkage and cell death due to apoptosis. AbstractBecause intravaginal pH is strongly acidic, it is important to investigate the effects of acidosis on cervical cancer cells. Recently, in response to strong acidosis, human cervical cancer HeLa cells were shown to exhibit necrosis after showing persistent cell swelling induced by Cl− influx. Since cation influx should be accompanied with Cl− influx to drive water inflow causing cell swelling, we here studied on the nature of acidotoxic cation conductance. The mRNA/protein expression was assessed by RT ‐PCR and Western blotting. Ionic currents were measured by patch‐clamping techniques. Cell counting/viability and colorimetric assays were applied to assess proliferation rate and caspase 3/7 activity, respectively. Cell volume and size were measured by electronic sizing and video‐microscopic measurements, respectively. Acid exposure enhanced TRPM7 activity endogenously expressed in HeLa cells and exogenously overexpressed in HEK293T cells. Gene silencing of TRPM7 abolished acid‐induced cell swelling and necrosis but rather induced activation of apoptotic caspase 3/7 in HeLa cells. Ove rexpression with the pore charge‐neu...
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research