APOL1 and Kidney Cell Function.

APOL1 and Kidney Cell Function. Am J Physiol Renal Physiol. 2019 Jun 26;: Authors: Kumar V, Singhal PC Abstract The APOL1 gene is unique to humans and gorillas and appeared approximately 33 million years ago. Since the majority of the mammals do not carry APOL1, it seems to be dispensable for kidney function. APOL1 renal risk variants (RRVs, G1 and G2) are associated with the development as well as the progression of chronic kidney diseases (CKDs) at higher rates in the population with African ancestry. Cellular expression of two APOL1 RRVs has been demonstrated to induce cytotoxicity, including necrosis, apoptosis, and pyroptosis in several cell types including podocytes; mechanistically, these toxicities were attributed to lysosomal swelling, potassium-depletion, mitochondrial dysfunction, autophagy blockade, PKR activation, UBD degradation, and ER stress; notably, these effects were found to be dose-dependent and occurred only in overtly APOL1 RRVs-expressing cells. However, the cellular protein expressions as well as circulating blood levels of APOL1RRVs were not elevated in patients suffering from APOL1 RRVs-associated CKDs. Therefore, a question arises whether it is the gain or loss of function on the part of APOL1 RRVs contributing to kidney cell injury. The question seems to be more pertinent after the recognition of the role of APOL1 non-risk (NR, G0) in the transition of parietal epithelial cells (PECs) and preservation of ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research