| First Author | Lieberthal W | Year | 2013 |
| Journal | BMC Nephrol | Volume | 14 |
| Pages | 251 | PubMed ID | 24228806 |
| Mgi Jnum | J:277391 | Mgi Id | MGI:6330943 |
| Doi | 10.1186/1471-2369-14-251 | Citation | Lieberthal W, et al. (2013) Susceptibility to ATP depletion of primary proximal tubular cell cultures derived from mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK. BMC Nephrol 14:251 |
| abstractText | BACKGROUND: The purpose of this study was to determine whether AMPK influences the survival of primary cultures of mouse proximal tubular (MPT) cells subjected to metabolic stress. Previous studies, using an immortalized MPT cell line, suggest that AMPK is activated during metabolic stress, and ameliorates stress-induced apoptosis of these cells. METHODS: Primary MPT cells were cultured from AMPK knockout (KO) mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK. MPT cells were subjected to ATP depletion using antimycin A. RESULTS: Surprisingly, there was no difference in the amount of death induced by metabolic stress of MPT cells from either type of AMPK KO mice compared to its WT control. Moreover, inhibition of the activity of the alpha1 isoform in primary MPT cells from alpha2-/- mice (pharmacologically, via compound C) or inhibition of the alpha2 isoform in primary MPT cells from alpha1-/- mice (molecularly, via knockdown) both decreased cell viability equivalently in response to metabolic stress. The explanation for this unexpected result appears to be an adaptive increase in expression of the non-deleted alpha-isoform. As a consequence, total alpha-domain expression (i.e. alpha1 + alpha2), is comparable in kidney cortex and in cultured MPT cells derived from either type of KO mouse versus its WT control. Importantly, each alpha-isoform appears able to compensate fully for the absence of the other, with respect to both the phosphorylation of downstream targets of AMPK and the amelioration of stress-induced cell death. CONCLUSIONS: These findings not only confirm the importance of AMPK as a pro-survival kinase in MPT cells during metabolic stress, but also show, for the first time, that each of the two alpha-isoforms can substitute for the other in MPT cells from AMPK KO mice with regard to amelioration of stress-induced loss of cell viability. |
